Pyrrolylacylpiperidine amine compounds and their uses

Abstract

The present invention belongs to the technical field of antibacterial drugs, and discloses pyrrolylacylpiperidine amine compounds and their uses.Specifically, the present invention relates to pyrrolylacylpiperidine amine compounds and their pharma- ceutically acceptable salts, and their uses in the manufacture of antibacterial drugs, antimycoplasma drugs, or antichlamydia infection drugs.The compounds have the structure shown in the following general formula: [Formula 1] TIFF2024522035000026.tif35140

Description

[Technical field]

[0001] The present invention belongs to the technical field of antibacterial agents, and specifically relates to pyrrolylacylpiperidine amine compounds and pharma- ceutically acceptable salts thereof, and their use as antibacterial agents, antimycoplasma agents, or antichlamydia infection agents. [Background technology]

[0002] Bacterial infections are caused by pathogenic or opportunistic bacteria that invade the body, grow, and produce toxins and other metabolic products. Bacterial infections are one of the major factors that harm human health, and the emergence of bacterial drug resistance in recent years has further posed a challenge to global public health. Currently, the super-resistant bacteria "ESCAPE" include Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae, which have already posed a serious threat to human health. With the overuse of antibiotics and the evolution of the bacteria themselves, we are facing a situation where there are no drugs that can be used against these super-resistant bacteria in clinical practice. Therefore, research and development of antibacterial drugs with new mechanisms of action is urgently needed.

[0003] Gyr B / Par E dual target inhibitors against DNA gyrase Gyr B subunit and topoisomerase IV Par E subunit have the following advantages in the research and development of antibacterial drugs: (1) They can simultaneously inhibit two bacterial targets, and the risk of drug resistance is low. (2) They have a bactericidal mechanism. (3) The antibacterial activity of novobiocin, a Gyr B / Par E inhibitor, has historically undergone clinical validation. Therefore, it is feasible to develop antibacterial drugs against this target to a certain extent. However, such Gyr B / Par E inhibitors also have the following problems in their research and development as antibacterial drugs: 1. Many compounds have good enzyme inhibitory activity but no in vitro antibacterial activity. 2. Many compounds do not show in vivo antibacterial activity or have poor pharmacokinetic properties. 3. The majority of compounds only inhibit the growth of gram-positive bacteria, and have no or low activity against gram-negative bacteria. For these reasons, there are no Gyr B / Par E dual target inhibitors on the market yet, except for novobiocin (which was discontinued after its release). Structural optimization of the Gyr B / Par E inhibitors currently under investigation and development of new structural types of Gyr B / Par E inhibitors are expected to increase their potential as drugs for this target.

[0004] DS2969 is a Gyr B / Par E dual target inhibitor developed by Daiichi Sankyo Pharmaceutical Co., Ltd. It has relatively good antibacterial activity and drug discovery potential, and is currently undergoing phase I clinical research. It is mainly used to treat infections caused by Clostridium difficile (WO2017056012). However, it needs further improvement in activity against in vitro positive bacteria (Staphylococcus aureus ATCC 29213, MIC = 0.2ug / mL), and has disadvantages such as low activity against gram-negative bacteria (Escherichia coli ATCC25922, MIC = 32ug / mL). In addition, AZD5099 (J. Med. Chem. 57, 6060-6082) developed by AstraZeneca was also in clinical research, but the clinical trial was discontinued due to a high coefficient of variation of in vivo exposure, a risk of mitochondrial damage, and low activity against gram-negative bacteria (Escherichia coli ATCC25922, MIC = 32ug / mL).

[0005] [ka] Summary of the Invention

[0006] The present invention aims to solve the deficiencies of Gyr B / Par E inhibitors in the prior art, and to provide broad-spectrum pyrrolylacylpiperidine amine compounds having higher antibacterial activity, antimycoplasmal activity or antichlamydial activity and superior drug designability, as well as pharma- ceutically acceptable salts thereof, and their use as antibacterial / antimycoplasmal / antichlamydial infection drugs. [Brief description of the drawings]

[0007] [Figure 1] Compound-induced tolerance curve. [Diagram 2] Mouse in vivo drug efficacy survival curve (1). [Diagram 3] Mouse in vivo drug efficacy survival curve (2). [Figure 4] This is a curve when administered intragastricly to mice. [Diagram 5] This is a survival curve of an acute toxicity test in mice. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] The present invention provides the following technical solutions:

[0009] A first aspect of the present invention provides pyrrolylacylpiperidine amine compounds having the structure shown in general formula I, and pharma- ceutically acceptable salts or stereoisomers thereof: [ka] (wherein R1, R5, and R6 each independently represent H, halogen, hydroxy, amino, nitro, cyano, carboxyl, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Alkylamino, di(C 1~6 Alkyl)amino, hydroxy C 1~6 Alkyl, Amino C 1~6 Alkyl, haloC 1~6 Alkyl or haloC 1~6 alkoxy; R2 is H, halogen, hydroxy, amino, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Alkylthio, HaloC 1~6 Alkyl, haloC 1~6 Alkoxy, HaloC 1~6 Alkylthio, C 1~6 Alkylamino, di(C 1~6 Alkyl)amino, Amino C 1~6 Alkoxy, Amino C 1~6 cycloalkoxy; R3 and R4 are each independently H, C 1~6 Alkyl, haloC 1~6 alkyl, or R and R together with the carbon atom to which they are attached are selected from C 3~8 Cycloalkyl or C 3~8 Constituting a heterocycloalkyl, A is selected from phenyl or 5-8 membered heteroaryl, optionally substituted by 1-4 Q1; Q1 is H, halogen, hydroxy, amino, nitro, cyano, carboxyl, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Alkylthio, C 1~6 Alkylamino, di(C 1~6 Alkyl)amino, hydroxy C 1~6 Alkyl, Amino C 1~6 Alkyl, Carboxyl C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 Alkoxy or haloC 1~6 alkylthio.

[0010] Further, the pyrrolylacylpiperidine amine compounds, and pharma- ceutically acceptable salts or stereoisomers thereof, have a structure represented by the general formula IA: [ka] (wherein R1, R5, and R6 are each independently H, halogen, hydroxy, amino, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkyl or haloC 1~6 alkoxy; R2 is H, halogen, hydroxy, amino, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Alkylthio, HaloC 1~6 Alkyl, haloC 1~6 Alkoxy, HaloC 1~6 Alkylthio, C 1~6 Alkylamino, di(C 1~6 Alkyl)amino, Amino C 1~6 Alkoxy, Amino C 1~6 cycloalkoxy; R3 and R4 are each independently H, C 1~6 Alkyl, haloC 1~6alkyl, or R and R together with the carbon atom to which they are attached are selected from C 3~6 Cycloalkyl or C 3~6 Constituting a heterocycloalkyl, A is selected from 5-6 membered heteroaryl optionally substituted by 1-3 Q1; Q1 is H, halogen, hydroxy, amino, nitro, cyano, carboxyl, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Alkylthio, C 1~6 Alkylamino, di(C 1~6 Alkyl)amino, hydroxy C 1~6 Alkyl, Amino C 1~6 Alkyl, Carboxyl C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 Alkoxy or haloC 1~6 alkylthio.

[0011] Furthermore, A is selected from thiazole, furan, thiophene, pyrazole, imidazole, oxazole, thiadiazole, pyridine, pyrazine, pyrimidine, or pyridazine; Furthermore, R1, R5, and R6 are each independently selected from H, fluorine, chlorine, bromine, hydroxy, amino, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoromethoxy, and trifluoroethoxy; R2 is selected from H, fluorine, chlorine, bromine, hydroxy, amino, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, methoxy, ethoxy, propoxy, isopropoxy, methylthio, ethylthio, propylthio, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoromethoxy, trifluoroethoxy, trifluoromethylthio or trifluoroethylthio, methylamino, dimethylamino, aminoethoxy, aminopropoxy, cyclopentyloxy; R3 and R4 are each independently selected from H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, trifluoromethyl, trifluoroethyl, or trifluoropropyl; or R3 and R4, together with the carbon atom to which they are attached, constitute cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, oxiranyl, oxetanyl, azetidinyl, azetidinyl, 1,4-dioxanyl, 1,3-dioxanyl, 1,3-dioxolanyl, tetrahydrofuryl, tetrahydropyrrolidinyl, tetrahydropyrazolidinyl, tetrahydroimidazolidinyl, tetrahydrothienyl, tetrahydrothiazolidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, hexahydropyridyl, piperazinyl, or morpholinyl; A is selected from furyl, thienyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, or 1,2,4,5-tetrazinyl.

[0012] Preferably, the compound has the structure shown in general formula IAa: [ka] wherein R2 is selected from H, fluorine, chlorine, bromine, hydroxy, amino, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, methoxy, ethoxy, propoxy, isopropoxy, methylthio, ethylthio, propylthio, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoromethoxy, trifluoroethoxy, trifluoromethylthio or trifluoroethylthio, methylamino, dimethylamino, aminoethoxy, aminopropoxy, cyclopentyloxy; R3 and R4 are each independently selected from H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, trifluoromethyl, trifluoroethyl, or trifluoropropyl; or R3 and R4 together with the carbon atom to which they are attached form cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; A is selected from furyl, thienyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, pyrazolyl, 1,3,4-oxadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, and 1,2,4,5-tetrazinyl.

[0013] Most preferably, the compound has the following structure:

[0014] [ka]

[0015] [ka]

[0016] A second aspect of the present invention provides a pharmaceutical composition comprising a pyrrolylacylpiperidine amine compound according to the first aspect, a pharma- ceutically acceptable salt and a pharma- ceutically acceptable carrier or excipient, and further comprising one or more other active ingredients.

[0017] The compound of the present invention or a pharmaceutical composition containing the same can be administered in the form of a unit dose, and the route of administration may be any of the intestinal or non-intestinal routes, such as oral, intravenous, intramuscular, subcutaneous, nasal, oral mucosa, ocular, pulmonary and airway, skin, vaginal, rectal, etc.

[0018] The dosage form may be a liquid dosage form, a solid dosage form, or a semi-solid dosage form. The liquid dosage form may be a solution (including true solution and colloidal solution), an emulsion (including o / w type, w / o type and multiple emulsion), a suspension, an injection (including water injection, powder injection and infusion), an eye drop, a nose drop, a lotion and an ointment, etc. The solid dosage form may be a tablet (including ordinary tablets, enteric tablets, buccal tablets, dispersible tablets, chewable tablets, effervescent tablets, oral disintegrating tablets), a capsule (including hard capsules, soft capsules, enteric capsules), a granule, a powder, a pellet, a drop pill, a suppository, a film, a patch, an aerosol (powder spray), a spray, etc. The semi-solid dosage form may be an ointment, a gel, a paste, etc.

[0019] The compounds of the present invention can be formulated into conventional formulations, sustained release formulations, controlled release formulations, targeted formulations, various particulate drug delivery systems, and the like.

[0020] In order to tablet the compound of the present invention, various excipients known to those skilled in the art can be widely used, including diluents, binders, wetting agents, disintegrants, lubricants, and cosolvents. The diluents can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc. The wetting agents can be water, ethanol, isopropanol, etc. The binders can be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, gum arabic pulp, gelatin pulp, sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, ethylcellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol, etc. The disintegrants can be dry starch, microcrystalline cellulose, low-substituted hydroxypropylcellulose, crosslinked polyvinylpyrrolidone, crosslinked sodium carboxymethylcellulose, sodium carboxymethylstarch, sodium bicarbonate and citric acid, polyoxyethylene sorbitan fatty acid ester, sodium dodecylsulfonate, etc. The lubricants and co-solvents may be talc powder, silica, stearates, tartaric acid, liquid paraffin, polyethylene glycol, and the like.

[0021] Furthermore, tablets can be coated, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, double-layer tablets, and multi-layer tablets.

[0022] To encapsulate the dosage unit, the active ingredient of the compound of the present invention may be mixed with a diluent and a cosolvent, and the mixture may be directly placed in a hard or soft capsule. The active ingredient of the compound of the present invention may be granulated or pelletized together with a diluent, a binder, and a disintegrant, and then placed in a hard or soft capsule. The same diluents, binders, wetting agents, disintegrants, and cosolvents as those used to prepare tablets of the compound of the present invention may also be used to prepare capsules of the compound of the present invention.

[0023] To prepare the compound of the present invention into an injection, water, ethanol, isopropyl alcohol, propylene glycol or a mixture thereof may be used as the solvent, and an appropriate amount of a solubilizer, co-solvent, pH adjuster, or osmotic pressure adjuster commonly used by those skilled in the art may be added. The solubilizer or co-solvent may be poloxamer, lecithin, hydroxypropyl-β-cyclodextrin, etc. The pH adjuster may be phosphate, acetate, hydrochloric acid, sodium hydroxide, etc. The osmotic pressure adjuster may be sodium chloride, mannitol, glucose, phosphate, acetate, etc. When preparing a lyophilized powder injection, mannitol, glucose, etc. may be added as a support.

[0024] If necessary, colorants, preservatives, fragrances, flavorings and other additives may be added to the pharmaceutical preparations.

[0025] In order to achieve the intended purpose and enhance the therapeutic effect, the drug or pharmaceutical composition of the present invention can be administered by any known administration method.

[0026] The dosage of the pharmaceutical composition of the compound of the present invention can vary widely depending on the nature and severity of the disease to be prevented or treated, the individual condition of the patient or animal, the administration route and dosage form, etc. In general, the suitable daily dosage range of the compound of the present invention is 0.1-50 mg / Kg body weight. The above dose can be administered in one dosage unit or divided into multiple dosage units depending on the administration schedule selected by the clinical experience of the doctor and the use of other treatment means. The compound or composition of the present invention can be used alone or in combination with other therapeutic drugs or symptomatic drugs. When there is a synergistic effect between the compound of the present invention and other therapeutic drugs, the dosage should be adjusted according to the actual situation.

[0027] The third aspect of the present invention provides the use of the pyrrolylacylpiperidine amine compounds and pharma- ceutically acceptable salts, stereoisomers, drug formulations and pharmaceutical compositions in the manufacture of antibacterial, antimycoplasmal or antichlamydial drugs, wherein the susceptible or drug-resistant Gram-positive bacteria are selected from Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, Clostridium difficile, Streptococcus, Streptococcus pneumoniae, Bacillus anthracis, Corynebacterium diphtheriae and Clostridium tetani, and the susceptible or drug-resistant Gram-negative bacteria are selected from Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Shigella, Corynebacterium diphtheriae, Bacillus proteus, Vibrio cholerae, Neisseria, Shigella spp., Klebsiella spp. The mycobacteria are selected from Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium leprae, the mycoplasma are selected from Mycoplasma pneumoniae, Ureaplasma urealyticum, Mycoplasma hominis, and Mycoplasma genitalium, and the chlamydia are selected from Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, and Chlamydia bovis.

[0028] The fourth aspect of the present invention provides a method for preparing the pyrrolylacylpiperidine amine compound and its pharma- ceutically acceptable salts and stereoisomers described in the first aspect. Pyrrolic acid a is used as a starting material, and is first condensed with 4-aminopiperidine (b) protected by t-butoxycarbonyl, and then the protecting group is removed to obtain intermediate d. The intermediate is then coupled with a brominated heterocycle (e) to obtain intermediate f, and finally, intermediate f is converted by a Grignard reaction or the like to obtain the target product. When synthesizing stereoisomers, they can be prepared using a fragment of chiral compound b.

[0029] [ka]

[0030] term In the present invention, the term "alkyl" refers to a group consisting of hydrocarbon atoms having a specified number of carbon atoms, and may be a straight or branched chain alkyl, "aminoalkyl" refers to an alkyl substituted with amino, and "haloalkyl" refers to an alkyl substituted with halogen. "Alkoxy" refers to a group in which an alkyl is linked to an oxygen atom. "Alkylamino" refers to a group in which an alkyl is linked to a nitrogen atom, and "dialkylamino" refers to a group in which two alkyls are each linked to a nitrogen atom. "Alkylthio" refers to a group in which an alkyl is linked to a sulfur atom.

[0031] Beneficial technical effects The present invention provides a pyrrolylacylpiperidine amine compound having excellent inhibitory activity against both gram-positive and gram-negative bacteria, mycobacteria, mycoplasma, and chlamydia. The inhibitory activity of the compound against all gram-positive and gram-negative bacteria, mycobacteria, mycoplasma, and chlamydia is clearly improved compared to DS2969, and the representative compound has activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Enterococcus faecium that is 15 times higher than that of the positive control DS2969. In addition, the representative compound showed more remarkable pharmacological activity than the positive control DS2969 in a mouse sepsis model infected with drug-resistant bacteria. Compared to the positive controls DS2969 and AZD5099, the representative compound has 32 times higher inhibitory activity against Escherichia coli, at least 8 times higher activity against Pseudomonas aeruginosa, and at least 4 times higher activity against Acinetobacter baumannii and Klebsiella pneumoniae. EXAMPLES

[0032] The present invention will be further described by the following examples, but the scope of the present invention is not limited to the following examples. Those skilled in the art will understand that various modifications and variations can be made to the present invention without departing from the spirit and scope of the present invention.

[0033] Example 1: Synthesis of 3,4-dichloro-N-{(3S,4R)-1-[6-(2-hydroxypropan-2-yl)pyridazin-3-yl]-3-methoxypiperidin-4-yl}-5-methyl-1H-pyrrole-2-carboxamide (Compound 1) [ka]

[0034] 3,4-Dichloro-5-methyl-1H-pyrrole-2-carboxylic acid (1g, 5.2mmol) was dissolved in about 6ml of DMSO, HATU (3g, 7.7mmol) and DIPEA (1.3ml, 7.7mmol) were added, and the mixture was stirred at room temperature for 30 minutes. (3S,4R)-4-amino-3-methoxypiperidine-1-carboxylate t-butyl (1.4g, 6.2mmol) was added, and the mixture was stirred at room temperature. The reaction was monitored by liquid chromatography-mass spectrometry. After the reaction was completed, an appropriate amount of water was added to the reaction solution to precipitate an organic precipitate, which was then filtered. The filter cake was washed with 0.1M HCl solution and saturated NaHCO3 solution in sequence to obtain the compound (3S,4R)-4-(3,4-dichloro-5-methyl-1H-pyrrole-2-carboxamide)-3-methoxypiperidine-1-carboxylate t-butyl as a white solid (yield 85%).

[0035] Compound (3S,4R)-4-(3,4-dichloro-5-methyl-1H-pyrrole-2-carboxamide)-3-methoxypiperidine-1-carboxylate t-butyl (1g, 2.5mmol) was dissolved in 1,4-dioxane (12ml), 6ml of 4M HCl / 1,4-Dioxane solution was added, stirred at 50℃, and monitored by liquid chromatography-mass spectrometry. After the reaction was completed, the reaction solvent was evaporated under reduced pressure to obtain compound 3,4-dichloro-N-((3S,4R)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide, which was used in the next step.

[0036] Compound 3,4-dichloro-N-((3S,4R)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (800 mg, 2.7 mmol) was dissolved in DMF (8 ml), compound 6-bromopyridazine-3-carboxylate methyl (700 mg, 3.2 mmol) and DIPEA (1.1 ml, 6.8 mmol) were added, and the mixture was stirred at 60° C. The reaction was monitored by liquid chromatography-mass spectrometry. After the reaction was completed, an appropriate amount of water was added to the reaction solution to precipitate an organic precipitate, which was filtered and dried to obtain compound 6-((3S,4R)-4-(3,4-dichloro-5-methyl-1H-pyrrole-2-carboxamide)-3-methoxypiperidin-1-yl)pyridazine-3-carboxylate methyl as a light brown solid (yield 71%).

[0037] The compound 6-((3S,4R)-4-(3,4-dichloro-5-methyl-1H-pyrrole-2-carboxamido)-3-methoxypiperidin-1-yl)pyridazine-3-carboxylate methyl ester (400 mg, 0.91 mmol) was dissolved in ultra-dry tetrahydrofuran (5 ml), and under nitrogen protection, CH3BrMg (3M) ethyl ether solution (1.7 ml, 4.6 mmol) was added dropwise at -5°C, and the mixture was stirred at room temperature after the dropwise addition. After completion of the reaction, the reaction mixture was quenched with saturated ammonium chloride solution, and the reaction mixture was extracted three times with ethyl acetate. The EA layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate, evaporated to dryness under reduced pressure, and subjected to column chromatography (dichloromethane:methanol=20:1) to obtain the compound 3,4-dichloro-N-{(3S,4R)-1-[6-(2-hydroxypropan-2-yl)pyridazin-3-yl]-3-methoxypiperidin-4-yl}-5-methyl-1H-pyrrole-2-carboxamide as a white solid (yield 46%).

[0038] ESI-MS (m / z): 442.13 [M+H] + . 1H NMR (500 MHz, Chloroform-d) δ 9.58 (s, 1H), 7.36 (d, J = 9.6 Hz, 1H), 6.99 (d, J = 9.6 Hz, 1H), 4.91 (dd, J = 15.0, 2.8 Hz, 1H), 4.35 (dq, J = 6.4, 3.1 Hz, 2H), 4.20 (d, J = 13.6 Hz, 1H), 3.60 - 3.54 (m, 1H), 3.44 (s, 3H), 3.18 - 3.08 (m, 2H), 2.28 (s, 3H), 2.00 - 1.90 (m, 2H), 1.57 (s, 6H).

[0039] Example 2: 3,4-dichloro-N-((3S,4R)-1-(5-(2-hydroxypropan-2-yl)-1,3,4-thiadiazol-2-yl)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (compound 2) [ka]

[0040] In accordance with the same method as in Example 1, the compound 3,4-dichloro-N-((3S,4R)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (Example 1) was reacted with 5-bromo-thiadiazole-2-carboxylate, and then reacted with CH3BrMg in a Grignard reaction, and the target product was obtained after purification. The yield was 70%.

[0041] ESI-MS (m / z): 448.36 [M+H] + . 1H NMR (400 MHz, Chloroform-d) δ 9.87 (s, 1H), 4.43 (ddd, J = 14.5, 3.2, 2.1 Hz, 1H), 4.36 - 4.23 (m, 1H), 3.83 (d, J = 13.5 Hz, 1H), 3.52 (q, J = 3.2 Hz, 1H), 3.47 (s, 3H), 3.29 (ddd, J = 13.4, 12.1, 3.1 Hz, 1H), 3.19 (dd, J = 14.4, 1.7 Hz, 1H), 2.88 (s, 1H), 2.28 (s, 3H), 2.12 - 1.96 (m, 1H), 1.94 - 1.83 (m, 1H), 1.67 (s, 6H).

[0042] Example 3: 3,4-dichloro-N-((3S,4R)-1-(5-(2-hydroxypropan-2-yl)pyrimidin-2-yl)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (compound 3) [ka]

[0043] According to the same method as in Example 1, compound 3,4-dichloro-N-((3S,4R)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (Example 1) was reacted with 2-bromo-pyrimidine-2-carboxylate, then Grignard reaction with CH3BrMg, and purified to obtain the target product, with a yield of 62%.

[0044] ESI-MS (m / z): 442.34 [M+H] + . 1H NMR (500 MHz, Chloroform-d) δ 9.92 (s, 1H), 8.43 (s, 2H), 7.28 (d, J = 8.2 Hz, 1H), 5.16 (d, J = 14.8 Hz, 1H), 4.77 (d, J = 14.9 Hz, 1H), 4.32 (d, J = 8.2 Hz, 1H), 3.48 (s, 1H), 3.43 (s, 3H), 3.01 (d, J = 13.9 Hz, 2H), 2.28 (s, 3H), 1.86 (d, J = 9.5 Hz, 2H), 1.57 (s, 6H).

[0045] Example 4: 3,4-dichloro-N-((3S,4R)-1-(5-(2-hydroxypropan-2-yl)pyrazin-2-yl)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (compound 4) [ka]

[0046] In accordance with the same method as in Example 1, the compound 3,4-dichloro-N-((3S,4R)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (Example 1) was reacted with 5-bromo-pyrazine-2-carboxylate, and then Grignard reaction with CH3BrMg was carried out, and the target product was obtained after purification. The yield was 65%.

[0047] ESI-MS (m / z): 442.34 [M+H] + . 1H NMR (500 MHz, Chloroform-d) δ 9.57 (s, 1H), 8.20 (s, 1H), 8.06 (s, 1H), 4.83 - 4.69 (m, 1H), 4.33 (s, 1H), 4.22 (d, J = 13.5 Hz, 1H), 3.57 - 3.48 (m, 1H), 3.43 (s, 3H), 3.09 (d, J = 10.3 Hz, 1H), 3.03 (d, J = 15.4 Hz, 1H), 2.28 (s, 3H), 1.93 (d, J = 13.0 Hz, 2H).

[0048] Example 5: 3,4-dichloro-N-((3S,4R)-1-(5-(2-hydroxypropan-2-yl)oxazol-2-yl)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (compound 5) [ka]

[0049] In accordance with the same method as in Example 1, the compound 3,4-dichloro-N-((3S,4R)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (Example 1) was reacted with 2-bromo-oxazole-5-carboxylate, and then Grignard reaction with CH3BrMg was carried out, and the target product was obtained after purification. The yield was 52%.

[0050] ESI-MS (m / z): 431.31[M+H] + . 1H NMR (400 MHz, Chloroform-d) δ 9.35 (s, 1H), 7.22 (d, J = 8.7 Hz, 1H), 6.99 (s, 1H), 4.41 (d, J = 14.3 Hz, 1H), 4.32 - 4.20 (m, 1H), 4.10 (d, J = 13.1 Hz, 1H), 3.45 (s, 4H), 3.14 - 2.98 (m, 2H), 2.28 (s, 3H), 1.94 (qd, J = 12.3, 11.7, 4.5 Hz, 1H), 1.82 (dd, J = 13.0, 4.5 Hz, 1H), 1.50 (s, 6H).

[0051] Example 6: 3,4-dichloro-N-((3S,4R)-1-(5-(2-hydroxypropan-2-yl)thiazol-2-yl)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (compound 6) [ka]

[0052] In accordance with the same method as in Example 1, the compound 3,4-dichloro-N-((3S,4R)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (Example 1) was reacted with 2-bromo-thiazole-5-carboxylate, and then Grignard reaction with CH3BrMg was carried out, and the target product was obtained after purification. The yield was 50%.

[0053] ESI-MS (m / z): 447.38[M+H] + . 1H NMR (500 MHz, Chloroform-d) δ 10.03 - 9.97 (m, 1H), 7.28 (s, 1H), 4.94 (s, 1H), 4.80 (s, 1H), 4.39 (dd, J = 27.6, 13.9 Hz, 1H), 4.29 (s, 1H), 3.90 (t, J = 16.0 Hz, 1H), 3.51 (s, 1H), 3.46 (s, 3H), 3.15 (dt, J = 24.3, 13.8 Hz, 2H), 2.28 (s, 3H), 2.11 - 1.95 (m, 3H), 1.91 - 1.81 (m, 1H), 1.28 (d, J = 31.3 Hz, 3H).

[0054] Example 7: 3,4-dichloro-N-((3S,4R)-1-(6-(1-hydroxycyclopentyl)pyridazin-3-yl)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (compound 7) [ka]

[0055] The compound 3,4-dichloro-N-((3S,4R)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (Example 1) was reacted with 3,6-dibromo-pyridazine, and then with cyclopentanone in the presence of n-butyllithium, and purified to obtain the target product. The yield was 54%.

[0056] ESI-MS (m / z): 468.38 [M+H] + . 1H NMR (500 MHz, Chloroform-d) δ 9.80 (s, 1H), 8.68 - 8.40 (m, 1H), 7.24 - 7.18 (m, 1H), 6.94 (d, J = 10.2 Hz, 1H), 5.07 - 4.93 (m, 1H), 4.34 (d, J = 11.3 Hz, 1H), 4.25 - 4.13 (m, 1H), 3.55 (s, 1H), 3.43 (s, 3H), 3.19 - 3.03 (m, 2H), 2.28 (s, 3H), 1.85 (d, J = 74.1 Hz, 4H), 1.25 (s, 4H).

[0057] Example 8: 3,4-dichloro-N-((3S,4R)-1-(6-(1-hydroxycyclohexyl)pyridazin-3-yl)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (compound 8) [ka]

[0058] In accordance with the same method as in Example 7, the compound 3,4-dichloro-N-((3S,4R)-3-methoxypiperidin-4-yl)-5-methyl-1H-pyrrole-2-carboxamide (Example 1) was reacted with 3,6-dibromo-pyridazine, and then reacted with cyclopentanone in the presence of n-butyllithium, and purified to obtain the target product. The yield was 64%.

[0059] ESI-MS (m / z): 482.41 [M+H] + . 11H NMR (500 MHz, Chloroform-d) δ 10.11 (s, 1H), 7.30 (d, J = 8.2 Hz, 1H), 7.08 (d, J = 9.3 Hz, 1H), 6.90 (d, J = 9.3 Hz, 1H), 4.93 (dt, J = 14.5, 2.9 Hz, 1H), 4.33 (ddt, J = 11.7, 8.6, 4.2 Hz, 1H), 4.16 - 4.07 (m, 1H), 3.53 (s, 1H), 3.43 (s, 3H), 3.15 - 3.03 (m, 2H), 2.82 (dd, J = 8.5, 6.7 Hz, 2H), 2.28 (s, 3H), 2.04 - 1.87 (m, 2H), 1.70 (p, J = 7.7 Hz, 2H), 1.40 (dd, J = 15.1, 7.6 Hz, 2H).

[0060] Experimental Example 1 In Vitro Antibacterial Activity Evaluation Test method: The in vitro antibacterial activity of the compounds against sensitive / drug-resistant strains was evaluated using the broth microdilution method, and the in vitro antibacterial activity of the compounds against various strains was tested. The specific operation steps are as follows: A sterile 96-well plate was placed on a clean bench, 200 μL of diluted bacterial solution was added to the first row, and 100 μL of bacterial solution was added to each row from the second row onwards. 4 μL of the test product solution with a concentration of 5 mg / mL dissolved in DMSO was added sequentially to each well in the first row, and a blank control group (no addition) and a positive drug group (levofloxacin with a concentration of 5 mg / mL) were set up, and each sample was repeated three times. After the sample addition, 128 μL of sample was added from the previous row to the next row in order using an 8-channel micropipette to perform a 2-fold gradient dilution. When adding to the last well, the sample was mixed uniformly and 100 μL of liquid was aspirated, and the compound concentrations in each well after dilution were 128, 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25, 0.125, 0.06, 0.03, 0.015, and 0.008 μg / mL, respectively. The 96-well plate was cultured in a 37°C incubator for 18 hours, and the growth of bacteria in each well was observed. For each compound, the concentration of the compound corresponding to the first well where no bacterial growth was observed, counting backward from the well where the sample was added, was determined as the minimum bacteriostatic concentration (MIC: Minimal Inhibitory Concentration) of the compound.

[0061] Results: From Tables 1, 2, and 3 below, the compounds showed very strong in vitro antibacterial activity, among which compound 1 and compound 2 had activity against Gram-positive bacteria that was more than 15 times higher than DS2969 and also stronger than the control drug levofloxacin, activity against Gram-negative bacteria that was at least 4 times and up to 32 times higher than DS2969 and AZD5099, and activity against Clostridium difficile that was stronger than DS2969 and the positive control drug vancomycin.

[0062] [Table 1]

[0063] [Table 2]

[0064] [Table 3]

[0065] Experimental Example 2 In vitro induced drug resistance evaluation of compound 1 Test method: The MIC values ​​of compound 1 and the control compound DS2969 against Staphylococcus aureus ATCC 29213 were determined using the broth microdilution method recommended in the Clinical and Laboratory Standards Institute (CLSI) antimicrobial susceptibility testing procedure.

[0066] After measuring the MIC value, the bacteria at the sub-MIC concentration (1 / 2 MIC) was collected and diluted to a concentration of 10 5 The bacterial suspension was adjusted to CFU / mL and the following MIC value test was performed. After 24 hours of incubation, the bacterial suspension with the drug sub-MIC concentration (1 / 2 MIC) was used to prepare a bacterial suspension and perform another MIC test. This process was repeated 20 times and the MIC value of each test was recorded.

[0067] The MIC values ​​of compound 1 and DS2969 in inducing 20 generations of S. aureus ATCC29213 were recorded with the induced bacterial number on the horizontal axis and the MIC value on the vertical axis (shown in Figure 1 ).

[0068] Results: After 20 passages, the MIC value of compound 1 was less than 1.0 μg / mL, whereas the MIC value of the positive control drug DS2969 was 16 μg / mL.

[0069] Experimental Example 3: In vivo antibacterial activity evaluation in mice Experimental animals: Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd., ICR mice, weight 20-22g, equal weight, half male and half female.

[0070] Modeling: Staphylococcus aureus (MRSA, ATCC 43300) infection sepsis model Modeling method: 2×10 7 -8×10 6 Mice were infected with Staphylococcus aureus (MRSA, ATCC 43300) at CFU / mL (diluted with 5% sterilized yeast solution) to form a mouse sepsis model (0.5 mL of the bacterial solution was injected intraperitoneally per mouse).

[0071] Experimental scheme: Compound 1 and the positive drug were dissolved in DMSO, then diluted with other solvents, with the solvent ratio being saline:Tween80:DMSO=9:0.5:0.5. Mice were divided into 5 groups, half male and half female, with 4 mice each. The treatment group was intravenously injected, subcutaneously injected, and intragastrically administered 0.4mL of 2.5mg / mL compound solution at a dose of 50mg / kg one hour after modeling. The negative control group was injected with 0.4mL of blank solvent after modeling, and the positive control group was subcutaneously injected with the positive drug DS2969 at the same dose as the compound group after modeling, and the survival rate of the mice was observed for 14 days.

[0072] Results: Referring to FIG. 2, compound 1 had significant in vivo antibacterial activity, and showed better antibacterial activity than DS2969.

[0073] Using the same model, the efficacy of Compound 1 was further investigated when administered intragastrically at a lower dose. As shown in Figure 3, the ED 50 ED of DS2969 is 5 mg / kg, 50 was greater than 10 mg / kg.

[0074] Experimental Example 4 In vivo pharmacokinetic study in mice Experimental animals: Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd., ICR mice, weight 20-22g, equal weight, half male and half female.

[0075] Experimental scheme: Compound 1 was administered intragastrically at a dose of 150 mg / kg (solvent: physiological saline: Tween 80: DMSO = 9: 0.5: 0.5). Blood samples were taken from the orbit or from the eyeball at 10 minutes, 20 minutes, 30 minutes, 1 hour, 3 hours, 5 hours, 8 hours, 24 hours, 36 hours, and 48 hours after administration. Blood concentrations were measured by UPLC, drug-time curves were plotted, and important pharmacokinetic parameters were calculated.

[0076] Results: The drug-time curve shown in Figure 4 and the important pharmacokinetic parameters shown in Table 3 show that the half-life is 9.2 hours and the bioavailability is 86%, indicating that the blood drug concentration of compound 1 in the body can be maintained for a relatively long time. Moreover, compound 1 is well absorbed in the body, which can provide good therapeutic effects.

[0077] [Table 4]

[0078] Experimental Example 5: In vivo acute toxicity test in mice Experimental animals: Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd., ICR mice, weight 20-22g, equal weight, half male and half female.

[0079] Experimental scheme: Compound 1 (solvent: physiological saline: Tween 80: DMSO = 9: 0.5: 0.5) was administered via tail vein, abdominal cavity, and stomach, respectively, and the survival rate of mice was observed for 14 days. The tail vein administration group consisted of 10 mice, half male and half female. The stomach administration group and abdominal cavity administration group consisted of 4 mice, half male and half female.

[0080] Results: As shown in Figure 5, the 14-day survival rate was 60% in the 95 mg / kg tail vein administration group, 100% in the 200 mg / kg intraperitoneal administration group, and 75% in the 800 mg / kg intragastric administration group.

Claims

**Claim 1** A pyrrolyl acyl piperidine amine compound having a structure represented by General Formula I, and a pharmaceutically acceptable salt or stereoisomer thereof. 【Chemical 1】 (Here, R １ , R ５ , R ６ are each independently H, halogen, hydroxy, amino, nitro, cyano, carboxyl, C １～６ alkyl, C １～６ alkoxy, C １～６ alkylamino, di(C １～６ alkyl)amino, hydroxyC １～６ alkyl, aminoC １～６ alkyl, haloC １～６ alkyl, or haloC １～６ alkoxy, and are selected from R ２ is selected from H, halogen, hydroxy, amino, C １～６ alkyl, C １～６ alkoxy, C １～６ alkylthio, halo C １～６ alkyl, halo C １～６ alkoxy, halo C １～６ alkylthio, C １～６ alkylamino, di(C １～６ alkyl)amino, amino C １～６ alkoxy, amino C １～６ cycloalkyloxy, R ３ and R ４ are each independently H, C １～６ alkyl, halo C １～６ alkyl, or R ３ and R ４ together with the carbon atoms to which they are attached form a C ３～８ cycloalkyl or C ３～８ heterocycloalkyl, A is selected from phenyl which may be substituted by 1 to 4 Q1s or 5- to 8-membered heteroaryl, Q1 is selected from H, halogen, hydroxy, amino, nitro, cyano, carboxyl, C １～６ alkyl, C １～６ alkoxy, C １～６ alkylthio, C １～６ alkylamino, di(C １～６ alkyl)amino, hydroxyC １～６ alkyl, aminoC １～６ alkyl, carboxylC １～６ alkyl, haloC １～６ alkyl, haloC １～６ alkoxy, or haloC １～６ alkylthio. **Claim 2** The pyrrolyl acyl piperidine amine compound according to Claim 1, having a structure represented by General Formula IA, and a pharmaceutically acceptable salt or stereoisomer thereof. [Chemical 2] (Here, R １ , R ５ , R ６ is independently selected from H, halogen, hydroxy, amino, C １～６ alkyl, C １～６ alkoxy, haloC １～６ alkyl, or haloC １～６ alkoxy, and R ２ is selected from H, halogen, hydroxy, amino, C １～６ alkyl, C １～６ alkoxy, C １～６ alkylthio, haloC １～６ alkyl, haloC １～６ alkoxy, haloC １～６ alkylthio, C １～６ alkylamino, di(C １～６ alkyl)amino, aminoC １～６ alkoxy, aminoC １～６ cycloalkoxy, R ３ and R ４ are each independently selected from H, halogen, C １～６ alkyl, halo C １～６ alkyl, or R ３ and R ４ together with the carbon atoms to which they are attached form a C ３～６ cycloalkyl or a C ３～６ heterocycloalkyl, A is selected from 5- to 6-membered heteroaryl which may be substituted by 1 to 3 Q1s, Q1 is selected from H, halogen, hydroxy, amino, nitro, cyano, carboxyl, C １～６ alkyl, C １～６ alkoxy, C １～６ alkylthio, C １～６ alkylamino, di(C １～６ alkyl)amino, hydroxyC １～６ alkyl, aminoC １～６ alkyl, carboxylC １～６ alkyl, haloC １～６ alkyl, haloC １～６ alkoxy, or haloC １～６ alkylthio. **Claim 3** A is selected from furyl, thienyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, or 1,2,4,5-tetrazinyl which may be substituted by 1 to 2 Q1s. The pyrrolyl acyl piperidine amine compound according to any one of Claims 1 to 2, and a pharmaceutically acceptable salt or stereoisomer thereof. **Claim 4** R １ 、R ５ 、R ６ are each independently selected from H, fluorine, chlorine, bromine, hydroxy, amino, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoromethoxy, or trifluoroethoxy, R ２ is selected from H, fluorine, chlorine, bromine, hydroxy, amino, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, methoxy, ethoxy, propoxy, isopropoxy, methylthio, ethylthio, propylthio, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoromethoxy, trifluoroethoxy, trifluoromethylthio, or trifluoroethylthio, methylamino, dimethylamino, aminoethoxy, aminopropoxy, cyclopentyloxy, R ３ and R ４ are each independently selected from H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, trifluoromethyl, trifluoroethyl, or trifluoropropyl, or R ３ and R ４ together with the carbon atoms to which they are attached form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxiranyl, oxetanyl, azetidinyl, azetidinyl, 1,4-dioxanyl, 1,3-dioxanyl, 1,3-dioxolanyl, tetrahydrofuryl, tetrahydropyrrolidinyl, tetrahydropyrazolidinyl, tetrahydroimidazolidinyl, tetrahydrothienyl, tetrahydrothiazolidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, hexahydropyridyl, piperazinyl, or morpholinyl, A is selected from furyl, thienyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, or 1,2,4,5-tetrazinyl. The pyrrolyl acyl piperidine amine compound according to any one of Claims 1 to 2, and a pharmaceutically acceptable salt or stereoisomer thereof. **Claim 5** The pyrrolyl acyl piperidine amine compound according to any one of Claims 1 to 2, having a structure represented by General Formula IAa, and a pharmaceutically acceptable salt. [Chemical Formula 3] (Here, R ２ is selected from H, fluorine, chlorine, bromine, hydroxy, amino, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, methoxy, ethoxy, propoxy, isopropoxy, methylthio, ethylthio, propylthio, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoromethoxy, trifluoroethoxy, trifluoromethylthio, or trifluoroethylthio, methylamino, dimethylamino, aminoethoxy, aminopropoxy, cyclopentyloxy, R ３ and R ４ are each independently selected from H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, trifluoromethyl, trifluoroethyl, or trifluoropropyl, or R ３ and R ４ together with the carbon atoms to which they are attached form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, A is selected from furyl, thienyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, pyrazolyl, 1,3,4-oxadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, or 1,2,4,5-tetrazinyl.)

6. The pyrrolyl acyl piperidine amine compound and pharmaceutically acceptable salt according to Claim 1, characterized by having the following structure. 【Chemical Formula 4】 [Chemical Formula 5]

7. A pharmaceutical composition comprising the pyrrolyl acyl piperidine amine compound according to Claim 1, and a pharmaceutically acceptable salt or stereoisomer thereof, and one or more pharmaceutically acceptable carriers or excipients.

8. The pharmaceutical composition according to Claim 7, further comprising one or more other pharmacologically active ingredients.

9. Use of the pyrrolyl acyl piperidine amine compound according to Claim 1 or 2, and a pharmaceutically acceptable salt or stereoisomer thereof, or the pharmaceutical composition according to Claim 7 or 8, in the manufacture of a drug for treating a bacterial infection, mycoplasma infection or chlamydia infection.

10. The use according to Claim 9, wherein the bacterium is selected from sensitive or drug-resistant Gram-positive bacteria, Gram-negative bacteria and mycobacteria, the mycoplasma is selected from sensitive or drug-resistant mycoplasmas, and the chlamydia is selected from sensitive or drug-resistant chlamydias.

11. The Gram-positive bacteria are selected from Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, Clostridium difficile, Streptococcus, Streptococcus pneumoniae, Bacillus anthracis, Corynebacterium diphtheriae, and Clostridium tetani. The Gram-negative bacteria are selected from Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Shigella dysenteriae, Corynebacterium diphtheriae, Proteus, Vibrio cholerae, Neisseria, Shigella, Klebsiella pneumoniae, Bacteroides vulgatus, Bordetella pertussis, and Haemophilus influenzae. The mycobacteria are selected from Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium leprae. The mycoplasmas are selected from Mycoplasma pneumoniae, Ureaplasma urealyticum, Mycoplasma hominis, and Mycoplasma genitalium. The chlamydiae are selected from Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, and Chlamydia abortus. The use according to claim 10, characterized in that it is so selected.

Images