JPS62242687A - Substituted benzoxazino and substituted benzothiazinorifamycin derivative - Google Patents

Abstract

NEW MATERIAL:A compound of formula I or formula II [X<1> is O or S; R<1> is OH, 1-3C alkoxy, group of formula III-V (R<2> is H or 1-3C alkoxy; R<3> is H, 1-3C alkyl or phenyl; R<4> is 1-3C alkyl, phenyl, -CH2CF3, etc.; R<12> is H, 1-3C alkyl or carboxyl), etc.] and its salt. USE:An antibacterial agent having low toxicity. PREPARATION:The objective compound can be produced by using a rifamycin derivative of formula VI or VII as a starting raw material, reacting the derivative with a compound of formula H2N-R<1> in an organic solvent such as methanol at a temperature between -20 deg.C and the boiling point of the solvent in the presence of an acid such as acetic acid for 10min-1 week, removing the reagent and reaction solvent, etc., from the reaction product and purifying the obtained crude product by column chromatography, etc.

Description

[Detailed description of the invention]

(Industrial Application Field) The present invention relates to a novel famycin derivative or a salt thereof, a method for producing the same, and an antibacterial agent containing the same as an active ingredient. More specifically, the present invention relates to the formula (Il or the formula CH, CH8 (wherein, XI represents an oxygen atom or a sulfur atom, and R1
represents a group represented by a hydroxyl group, an alkoxy group having 1 to 8 carbon atoms, an alkoxy group having 8 carbon atoms), a kyl group, or a phenyl group; RIS, Re is the same or different hydrogen atom or alkyl group having 1 to 8 carbon atoms), X2 is an oxygen atom or NR7 (R7 is a hydrogen atom, an amino group, Alkyl group having 1 to 8 carbon atoms, -(
CH2) a group represented by 20H or a group represented by]) (a R8 is an alkyl group having 1 to 3 carbon atoms, (CH2)XNR'
(X represents 1 to 8, y represents 2 or 8, R9 group,
Alkoxy group having 1 to 6 carbon atoms, CONH2 table b sat
A new rifamycin derivative represented by L M, NHR'' (R represents a group represented by a hydrogen atom or carbon, a group represented by H8, a group represented by NHCNH2) The present invention relates to a salt thereof, a method for producing the same, and an antibacterial agent containing the salt as an active ingredient. (Prior Art) The famycin derivative according to the present invention is a new compound that has not been described in any literature. (Means and Effects for Solving the Problems) The present inventors have added the formula

[Ma]82N
-R1[maJ (R1 is as described above) by reacting the compound represented by the formula [IJ! or a novel rifamycin derivative represented by formula [II], and found that the obtained derivative has strong antibacterial activity,
We have arrived at the present invention. The novel rifamycin derivative represented by the formula [IJ or formula (2) according to the present invention] can be used in many organic solvents, halogenated hydrocarbons such as chloroform and methylene chloride; alcohols such as methyl alcohol and ethyl alcohol; methyl formate; , esters such as ethyl acetate; aromatic hydrocarbons such as benzene and toluene; and ethers such as tetrahydrofuran and dioxane. The novel rifamycin derivative represented by formula m or formula l according to the present invention can form a salt with a base. Furthermore, among the novel rifamycins represented by formula (Il or formula [II]), those containing a basic residue in R1 can form salts with acids. Bases or acids that can be used include:
Any compound capable of forming a salt with the rifamycin derivative represented by formula I11 or formula [I1] can be selected. Specific examples of salts with bases include (1) metal salts, especially salts with alkali metals and alkaline earth metals, (2) ammonium salts, (3) amine salts, especially methylamine, ethylamine, diethylamine, There are salts with triethylamine, pyrrolidine, morpholine, hexamethyleneimine, etc. Examples of salts with acids include (1) salts with mineral acids such as sulfuric acid and hydrochloric acid, and (2) salts with organic acids such as p-)luenesulfonic acid, trifluoroacetic acid and acetic acid. The novel rifamycin derivatives represented by the formula [IJ or formula (2) according to the present invention can be prepared as follows. That is, the rifamycin:/ii 4 compound represented by the formula IIl or the above is dissolved in one of the available solvents such as methanol, ethanol, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, and -
A compound represented by the formula [ma]H,2NR' [maj (R1 is as described above) is heated at a humidity of 20''C to the boiling point of the solvent in the presence or absence of an acid such as acetic acid. It can be obtained by reacting for minutes to one week.As the reaction solvent, methanol, ethanol, isopropyl alcohol, tetrahydrofuran, pyridine, acetone, ethyl acetate, chloroform, N,N-dimethylformamide, dimethyl sulfoxide, etc. can be used. can be done.Reaction time is 10
However, the optimal reaction time varies depending on the reaction conditions such as the type and amount of the compound represented by the above formula [M] used in the reaction and the reaction temperature, so the optimal reaction time depends on the progress of the reaction. It should be determined by tracking using thin layer chromatography. The rifamycin derivative represented by the formula [II] can be converted into the rifamycin derivative represented by the formula [II] by reduction with a reducing agent such as ascorbic acid. Conversely, by oxidizing the rifamycin derivative represented by formula (5) with an oxidizing agent such as manganese dioxide, a rifamycin derivative represented by formula [II] can be obtained. Reducing agents that can be used in the above reduction reaction include ascorbic acid, sodium hydrosulfide, and the like. In addition, the oxidizing agents used in the above oxidation reaction include air, oxygen, manganese dioxide, lead dioxide,
Examples include silver oxide and potassium ferricyanide. In addition, the compound represented by formula [I], Famycin S
or 8-halogenolifamycin S and formula l (XI,
It can also be synthesized by reacting a compound represented by (R1 is as described above) or a salt thereof with zinc, silver, etc. Examples of 8-halogenolifamycin S that can be used in the reaction include 8-chlororifamycin 818-bromorifamycin S, 8-iodorifamycin S, and the like. As the reaction solvent, methanol, ethanol, isopropyl alcohol, tetrahydrofuran, pyridine, acetone, ethyl acetate, chloroform, benzene, toluene, N,N-dimethylformamide, dimethylsulfoxide, etc. can be used. The rifamycin derivative represented by formula [R3 or formula [II] according to the present invention can be relatively easily separated and purified from the reaction product. That is, an excess amount of the above H1 used in the reaction
! By removing reagents such as N R' (R1 is as described above), reaction solvent, etc., and purifying the obtained crude product by crystallization, column chromatography, etc., the desired rifamycin derivative can be obtained. can be obtained. Table 1 shows representative examples of the novel rifamycin derivatives represented by formula [II] according to the present invention, and Table 2 shows representative examples of the novel rifamycin derivatives represented by formula (2). In Tables 1 and 2, TR layer chromatography was performed using Merck's silica gel 60F IEFl 0 magnetic plate (2Gc11x2ocM). Nuclear magnetic resonance spectra were measured using tetramethylsilane as an internal standard and as a deuterated chloroform solution unless otherwise specified. Infrared absorption spectra were measured using the potassium bromide tablet method. (Leaving space below; ; Dawn: fd Base system A: Chloroform/acetone = 9/1B: Chloroform/acetone = 8/2C: Chloroform/methanol = 9/ID; Chloroform/methanol = 8/2E: Chloroform/methanol = 778F: Abbreviation in 3971 mm methanol / acetate S: 51G1ET D: DOUBLET T: TRIPLET Q: QUARTET M: MULTIPLET BR: BROAD * * *
Solvent: CDC1g+ dimethyl sulfoxide-d6
※※※8 Solvent: c, octB+ coscocp
a The rifamycin derivative according to the present invention weighs 1 gram! l
Shows strong antibacterial activity against A-type bacteria and acid-fast mK. The antibacterial activity of the novel rifamycin derivative according to the present invention was evaluated using the standard method of the Japanese Society of Chemotherapy [Journal of the Japanese Society of Chemotherapy]. Vol. 29, p. 76 (1981)]. Representative examples are shown in Table 8. As is clear from Table 8, the novel rifamycin derivatives of the present invention exhibit strong antibacterial activity against Guhum-positive bacteria and acid-fast bacteria. The derivative numbers in the table correspond to the derivative numbers in Tables 1 and 2. The novel rifamycin derivatives according to the present invention are
It was orally administered to mice at a rate of 4 mJ/Kg.
It was found that the novel rifamycin derivative according to the present invention has low toxicity without exhibiting any toxicity. The antibacterial agent formulation containing the novel rifamycin derivative of the present invention as an active ingredient may be a formulation for oral, enteral or parenteral administration. Specific formulations include tablets, capsules, fine granules, syrups, crude drugs, and ointments. As carriers for the formulations of antimicrobial agents according to the invention, organic or inorganic solid or liquid, usually inert, pharmaceutical carrier materials suitable for oral, rectal, or incubation administration are used. Specific examples include crystalline cellulose, gelatin, lactose, starch, magnesium stearate, talc, vegetable and animal fats and oils, gums, polyalkylene glycols. The proportion of antimicrobial agent of the invention to carrier in the formulation can vary between 0.2 and 100%. The antimicrobial agent according to the invention may also include other antimicrobial agents and other pharmaceutical agents that are compatible therewith. in this case,
It goes without saying that the antibacterial agent according to the invention does not have to be the main ingredient in the formulation. Antimicrobial agents according to the invention are generally administered at dosages that achieve the desired effect without side effects. The specific value should be determined by a doctor's judgment, but in general, the daily adult IQm, p ~ 1011, preferably 20m, 9
It would normally be administered at around 5Ii. The antibacterial agent of the present invention can be administered as a pharmaceutical preparation having a unit of lmJF to 511, preferably Bml to II, as an active ingredient. (Examples) In order to further clarify the understanding of the present invention, examples will be given and explained, but these are merely illustrative and do not limit the present invention. Example 1 Synthesis of Derivative 1 0.741 p-anisidine and 4-hydroxy-8-nitrobenzaldehyde LOO1 were mixed with 8 Gm
/ and heated to dissolve. After cooling, the precipitated crystals were separated and air-dried to obtain a condensate of 0.50.9. 25ml of the obtained crystals! The mixture was dissolved in ethanol, 25 m# of palladium on carbon (5%) was added, and hydrogenated at room temperature and pressure for 2 hours. After separating the propellant from P, the solvent was distilled off to give a yield of 0.46. I got a great impression of SF. The resulting residue was treated with rifamycin 80.
7 (20 m/l of tobenzene) was added and stirred overnight at 50°C. After concentrating the reaction mixture, 20 ml of methanol and 0.709 m of manganese dioxide were added and stirred at room temperature for 2 hours.Then, the reaction solution was filtered. The resulting p solution was concentrated to dryness.The 8i condensation to dryness was carried out twice using silica gel as a carrier.
717, the developing solvent is chlorophor A-7 setone =
85: 15, 9: 1) wIlIl from Ic
1 to obtain 0.05.9 of the desired red derivative 1. Example 2 Synthesis of Derivative 2 The desired derivative 2 was synthesized from rifamycin 8 1.851 to 1.01 using 0-methylhydroxylamine instead of p-anisidine in Example 1 and following the same procedure as in Example 1. I got .9. Implementation @ 8 Synthesis of derivative A 1.67.9 ml of 4-hydroxy-8-nitrobenzaldehyde and sodium borohydride in 40 m/ethanol
, go, and v were added and heated under reflux for 6 hours, and then the reaction mixture was poured into a large amount of water. The mixture was made acidic by adding 10% hydrochloric acid, and extracted with ethyl acetate. Dilute the extract with anhydrous methic acid)
After drying with Q ram, the solvent was distilled off. The obtained residue was purified by column chromatography using silica gel as a carrier (eluent was 7 tons of chloroformat = 95:5) to give 4-hydroxy-8-nitrobenzyl alcohol of 0.111. . The obtained 4-hydroxy-8-nitrobenzyl alcohol was mixed with 20ml of ethanol! Dissolved in Pudgeram carbon (
6%) 0.0? , 9 was added and hydrogenated at room temperature and pressure for 8 hours. llv! ! After removing the medium by filtration, the solvent was distilled off to 0.
82.5F 8-amino-4-hydroxybenzyl alcohol was obtained. Obtained 8-amino-4-hydroxybenzyl alcohol KIJfamycin 8 1.60JF
and 20 mA' of benzene were added, and the mixture was heated under reflux for 4 hours, and then, after concentration, 20 mA' of methanol and manganese dioxide t, oo, and p were added, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered, the solvent was distilled off, and the resulting residue was prepared using silica gel as a carrier fd7.47. Layered chromatography (n-butyl acetate (solvent: n-butyl acetate)) and column chromatography using silica gel as a carrier (eluent: chloroform-acetone = 95:5) were used to prepare FFI. A derivative A was obtained in which the derivative A is an oxygen atom and 4 is a formyl group. Example 4 Synthesis of Derivative 8 Derivative A0.811i obtained by the method of Example 3 was added to 20 ml of tetrahydrofufun (THF)! 2.2.2-)) Add 0.68 ml of 70% aqueous solution of lifluoroethylhydrazine! In addition, the mixture was allowed to react overnight at room temperature. Next, 1.60.9 g of manganese dioxide was added and stirred at room temperature for 1 hour. The reaction mixture was filtered, and the P solution was concentrated to dryness to obtain 1.14. A residue of F was obtained. This was purified by silica gel column chromatography twice (each eluent was chloroform-acetone = 19 = 1 and ethyl acetate-n-hexane = 1:1) to obtain the desired derivative 3.
I got toy. From the east Example 5 Synthesis of derivative 4 5! Using 1,1-dimethylhydrofudine instead of p-anisidine in Example 1, the same procedure was repeated to obtain 0.4 g of the desired derivative 4 from 8 g of rifamycin and 69.9 g of rifamycin.
I got F. Example 6 Synthesis of derivative 5 Rifamycin 8 was synthesized by the same procedure using N-aminopiperi instead of p-anisidine in Example 1.
4.41. 0.04 # of the desired derivative 6 was obtained from p. Example 7 Synthesis of derivative 6 Rifamycin 8 was synthesized by the same procedure using N-aminomorpholine in place of p-anisidine in Example 1.
The desired derivative 6 was obtained from 2.097F. Example 8 Synthesis of Derivative 7 The desired derivative 7 was synthesized from rifamycin 8 2.09,9 by using 1-amino-4-methylbiperazine instead of p-anisidine in Example 1. .28! I got it. Example 9 Synthesis of Derivative 8 The following procedure was carried out in the same manner using 2.2.2-trifluoroethylhydrazine in Example 4 and -t'; From derivative A0.811i obtained by the method of Example 8, 0.16.9 of the desired derivative 8 was obtained. Example 10 Synthesis of derivative 9 Instead of p-anisidine and 4-hydroxy-8-nitrobenzaldehyde in Example 1, hydroxylamine and 8-
Using hydroxy-4-nitrobenzaldehyde and the same procedure as in Example 1, 0.68.9% of the desired derivative 9 of rifamycin 84I was obtained. Example 11 Synthesis of Derivative 10 Rifamycin 8 4.0. The desired derivative lO from p is 2
．． I got 22JF. Example 12 Synthesis of derivative B N,N-dimethylformamide (DMF) 40m/3
-Hydroxy-4-nitrobenzaldehyde 10.0.
9 and dissolved sodium borohydride 4.54,
A solution of No. 9 in DMF was added dropwise at 60 m/m while stirring at a temperature, and the mixture was further stirred at room temperature for 2 hours. The solvent was distilled off from the reaction mixture to remove 800ml of water! added. This was acidified with hydrochloric acid, and the resulting precipitate was separated, washed with water, and dried to obtain 5.81 g of 3-hydroxy-4-nitrobenzyl alcohol. 8-Hydroxy-4-nitrobenzyl alcohol was dissolved in 209m/kg of ethanol and 0.29.9ml of palladium carbon (5%) was added at room temperature to 1.9Fl/am.
After removing the catalyst, activated carbon 6I was added and filtered, the solvent was distilled off, and 4-amino-8-
8.811 of hydroxybenzyl alcohol was obtained. The obtained 4-amino-8-hydroxybenzyl alcohol was reacted with famycin 8 16.7.9 in the same manner as in Example 3, and purified by post-treatment to obtain 5.8.
Derivative B having the formula [I:lK, where xl is an oxygen atom and 5' is a formyl group, was obtained. Example 18 Synthesis of derivative 11 Derivative B0.81.9 obtained by the method of Example 12 was converted into T
HF20ml! 0.81.9% of N,N-dimethylhydrazine was added, and the mixture was stirred and reacted at room temperature for 80 minutes. Next, 1.65 JI of manganese dioxide was added and heated to 80°C.
Stir for 1 minute. The reaction mixture was filtered, and the P solution was evaporated to dryness. The obtained residue was purified by silica gel column chromatography (eluent: ethyl acetate-n-hexane = 1:1) to obtain 0.61 J of the desired derivative 11. Example 14 Synthesis of derivative 12 Instead of N,N-dimethylhydrazine in Example 18, N-
Using aminopiperidine, the desired derivative 12 was converted from derivative B0.81,9 to 0.6 by the same operation.
I got 0.9. Example 15 Synthesis of derivative 18 Instead of N,N-dimethylhydrazine in Example 111, N
-7' Minomorpholine was used and the same operation was performed to obtain 0.56.9 of the target derivative 18 from derivative B0.81.9. ! , ll-Example 16 Synthesis of Derivative 14 Using 1-amino-4-methylpiperazine in place of hydroxylamine in Example 10, rifamycin 8 4.28! From i, remove the desired derivative 14, O1
I got 9. Example 17 Synthesis of Derivative 15 Using oxamic acid hydrazine in place of N,N-dimethylhydrazine in Example 13, and following the same procedure, the desired derivative 16 was synthesized from Derivative B0.81.9 to 0.8
9. I got SF. Example 18 Synthesis of derivative C 4-chloro-3-nitrobenzaldehyde 50.9 was added to an 800 m/aqueous solution of Na28.9H20194, ip and heated for 8 hours, then allowed to cool, and the reaction solution was extracted and washed with ether. . The aqueous layer was saturated with sodium chloride, and the resulting precipitate of 2-amino-4-formylthiophenol sodium salt was separated and dried to obtain a residue of 88.81. The obtained residue was dissolved in 600 mL of water, insoluble matter was separated by F, and a concentrated aqueous solution of zinc chloride was gradually added to the solution under water cooling. The resulting yellow precipitate was collected, washed with water and methanol, and then dried to obtain 29.1.9 of 2-choice minnow 4-formylthiophenol octopus lead salt. The obtained 2-amino-4-formylthiophenol lead salt 24.3I was crushed finely and suspended in 800 m/h of ethanol, and 8-bromolyfamycin 8 (JP-A-1986-1995)
Synthesized according to the method described in 599) by adding 100y to 8
Stir for hours. Insoluble matter was separated, the solvent of the D-i solution was distilled off under reduced pressure, and the residue was dissolved in chloroform and washed with water. Chloroform was distilled off under reduced pressure, and the resulting residue was transferred to Wakogel C! -200 as a carrier (eluent: hachloroformacetone = 95:6). In the formula [■] of 59.811, XI is a sulfur atom and 4' is a formyl group. Derivative C was obtained. Example 19 Synthesis of derivative 16 LOOml of derivative C5y obtained by the method of Example 18
! Hydroxylamine hydrochloride in ethanol solution 2.9
1 and 5ffl/acetic acid were added, and the mixture was stirred at room temperature for 6 hours to react. After the reaction is completed, 500 m5I! No. 1!
! ? After diluting with acid salt, the mixture was purified twice with water, once with dilute hydrochloric acid, once with water, and once with saturated saline, and then the solvent was distilled off under reduced pressure. The obtained residue was applied to Wakogel■0-20
Silica gel column chromatography using 0 as a carrier (
The eluate was subjected to chloroform-acetone (9:1) to obtain n fractions containing the target compound. The solvent of this fraction was evaporated under reduced pressure, and the resulting residue was subjected to silica gel column chromatography under the same conditions as above and treated in the same manner to obtain 2.4811 of the desired derivative 16. . Examples 20 to 57 Before synthesis of derivatives 17 to 54, derivative 17 was prepared by the same procedure as in Example 19 using the reagents shown in 4.
~54 was obtained. Example 58 Synthesis of derivative 55 4 and 9 0.8.9 and ethyl acetate flllOml! An aqueous solution of 1.811i L-ascorbic acid (8
ml was added and stirred at room temperature. The progress of the reaction was monitored by thin layer chromatography, and the reaction was quantitatively completed in 4.5 hours. The reaction mixture was washed twice with water and once with saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off and dried under reduced pressure to give 0.2 g of derivative 5.
I got 6. Example 59 Synthesis of derivative 56 Derivative 10 was used in place of derivative 9 in Example 68, and the desired derivative 56 was obtained from derivative 10 1.22.9 by the same procedure. Example 60 Synthesis of derivative 57 Using derivative 11 in place of derivative 9 in Example 68, and following the same procedure, the desired derivative 57 was converted from derivatives 110.8, 9 to o, oaI! Obtained. Example 61 Synthesis of Derivative 58 Derivative 12 was used in place of Derivative 9 in Example 58, and the same procedure was repeated to obtain 0.27.9 of the desired derivative 58 from Derivative 120.88I. Example 62 Synthesis of Derivative 59 Using Derivative 13 in place of Derivative 9 in Example 58, and following the same procedure, the desired derivative 69 was synthesized from Derivative 180.4JP to 0.18. I got F. Example 68 Synthesis of derivative 60 Derivative 14 was used instead of derivative 9 in Example 58, and 0.11.9 of the target derivative 60 was obtained from derivative 140.181 by the same procedure.

Claims (5)

[Claims] (1) A rifamycin derivative represented by the following formula [I] or formula [II] and a salt thereof. ▲There are mathematical formulas, chemical formulas, tables, etc.▼[I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼[II] {In the formula, X^1 represents an oxygen atom or a sulfur atom, and R
^1 is a hydroxyl group, an alkoxy group having 1 to 3 carbon atoms, ▲Numerical formula,
There are chemical formulas, tables, etc. ▼ (R^2 represents a hydrogen atom or an alkoxy group having 1 to 3 carbon atoms), ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (R^3 represents a hydrogen atom, a carbon number An alkyl group of numbers 1 to 8 with a prime number of 1 to 3, a phenyl group, a group represented by -CH_2CF_3, or a group represented by ▲There are mathematical formulas, chemical formulas, tables, etc. , tables, etc.▼(▲Mathematical formulas, chemical formulas,
There are tables, etc. ▼ indicates a 3- to 8-membered cyclic amino group with 2 to 7 carbon atoms, and R^5 and R^6 indicate the same or different hydrogen atoms or alkyl groups with 1 to 3 carbon atoms) There are groups represented by ▲mathematical formulas, chemical formulas, tables, etc.▼ [l, m are the same or different 1 to 4, X^2 is an oxygen atom or NR^7
(R^7 is a hydrogen atom, an amino group, an alkyl group having 1 to 3 carbon atoms, a group represented by -(CH_2)_2OH, or ▲
There are mathematical formulas, chemical formulas, tables, etc. There are groups represented by ▼ (indicates a group represented by , R^8 is an alkyl group having 1 to 3 carbon atoms, (CH_2)_xNR_^9_y (x represents 1 to 3, y represents 2 or 3, R^9 is an alkyl group having 1 to 3 carbon atoms, or NR^9_y is a group represented by ▲ (which has numerical formulas, chemical formulas, tables, etc.), an alkoxy group having 1 to 6 carbon atoms, a group represented by CONH_2, NHR^1^0 ( There are groups represented by ▲mathematical formulas, chemical formulas, tables, etc.▼(R^1^1 represents a hydrogen atom, a hydroxyl group, an amino group, or an alkyl group having 1 to 4 carbon atoms). nitro group), ▲There are mathematical formulas, chemical formulas, tables, etc.▼, furyl groups, thienyl groups, or ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Groups represented by ▲Mathematical formulas, chemical formulas, tables, etc. ▼(R^1^2 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a carboxyl group), ▲Mathematical formulas, chemical formulas, tables, etc. There is a group represented by ▼, ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ Groups represented by NHCNH_2, ▲ Numerical formulas, chemical formulas, tables, etc. ▼ Groups represented by or ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ Represents the group represented by. } (2) The rifamycin derivative and its salt according to claim 1, wherein in formula [I] or formula [II], X^1 is an oxygen atom. (3) The rifamycin derivative and its salt according to claim 1, wherein in formula [I] or formula [II], X^1 is a sulfur atom. (4) The following formula [III] or [IV] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [III] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [IV] (X^1 is an oxygen atom or a sulfur atom The rifamycin derivative represented by the formula [V]H_2N-R^
1[V] {R^1 is a hydroxyl group, an alkoxy group having 1 to 3 carbon atoms, ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (R^2 indicates a hydrogen atom or an alkoxy group having 1 to 3 carbon atoms) The groups represented, ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (R^3 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a phenyl group, R^4 represents an alkyl group having 1 to 3 carbon atoms, phenyl group, -
Groups represented by CH_2CF_3 or ▲There are mathematical formulas, chemical formulas, tables, etc.) Groups represented by ▲There are mathematical formulas, chemical formulas, tables, etc.
There are tables, etc. ▼ indicates a 3- to 8-membered cyclic amino group with 2 to 7 carbon atoms, and R^5 and R^6 indicate the same or different hydrogen atoms or alkyl groups with 1 to 3 carbon atoms) There are groups represented by ▲mathematical formulas, chemical formulas, tables, etc.▼ [l, m are the same or different 1 to 4, X^2 is an oxygen atom or NR^
7 (R^7 represents a hydrogen atom, an amino group, an alkyl group having 1 to 3 carbon atoms, a group represented by -(CH_2)_2OH, or a group represented by ▲There are mathematical formulas, chemical formulas, tables, etc.) ▲There are mathematical formulas, chemical formulas, tables, etc.▼[X^8 represents an oxygen atom or a sulfur atom, R^8 represents an alkyl group having 1 to 3 carbon atoms, (CH_2)_xNR ^9_y (x represents 1 to 3, y represents 2 or 3, R^9 represents an alkyl group having 1 to 3 carbon atoms, or NR^9_y is ▲There are mathematical formulas, chemical formulas, tables, etc.▼ A group represented by a group represented by ), an alkoxy group having 1 to 6 carbon atoms, a group represented by CONH_2, NHR^1^0 (R^1^0 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms) There are groups represented by (shown), ▲ mathematical formulas, chemical formulas, tables, etc. There are groups represented by ▼ (R^1^1 represents a hydrogen atom, a hydroxyl group, an amino group, or a nitro group), There are groups represented by ▼, furyl groups, thienyl groups, or ▲mathematical formulas, chemical formulas, tables, etc.▼
▲There are mathematical formulas, chemical formulas, tables, etc. ▼ (R^1^2 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a carboxyl group) , ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Groups represented by ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ Groups represented by NHCNH_2, ▲ Numerical formulas, chemical formulas, tables, etc. ▼ Groups represented by or ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ Represents a group represented by } A formula characterized by reacting a compound represented by [
I ] or formula [II] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [ I ] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [II] (In the formula, X^1 and R^1 are as described above. ) A method for producing a rifamycin derivative represented by (5) The following formula [I] or formula [II] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [ I ] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [II] (In the formula, X^1 is an oxygen atom or represents a sulfur atom, R
^1 is a hydroxyl group, an alkoxy group having 1 to 3 carbon atoms, ▲Numerical formula,
There are chemical formulas, tables, etc. ▼ (R^2 represents a hydrogen atom or an alkoxy group having 1 to 3 carbon atoms), ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (R^3 represents a hydrogen atom, a carbon number Represents an alkyl group having 1 to 3 carbon atoms or a phenyl group, R^4 is an alkyl group having 1 to 3 carbon atoms, a phenyl group, -
Groups represented by CH_2CF_3 or ▲There are mathematical formulas, chemical formulas, tables, etc.) Groups represented by ▲There are mathematical formulas, chemical formulas, tables, etc.
There are tables, etc. ▼ indicates a 3- to 8-membered cyclic amino group with 2 to 7 carbon atoms, and R^5 and R^6 indicate the same or different hydrogen atoms or alkyl groups with 1 to 3 carbon atoms) There are groups represented by ▲mathematical formulas, chemical formulas, tables, etc.▼ [l, m are the same or different 1 to 4, X^2 is an oxygen atom or NR^7
(R^7 is a hydrogen atom, an amino group, an alkyl group having 1 to 3 carbon atoms, a group represented by -(CH_2)_2OH, or ▲
There are mathematical formulas, chemical formulas, tables, etc. There are groups represented by ▼ (indicates a group represented by , R^8 is an alkyl group having 1 to 3 carbon atoms, (CH_2)_xNR^9_y (x represents 1 to 3, y represents 2 or 3, R^9 is an alkyl group having 1 to 3 carbon atoms, or NR^9_y is a group represented by ▲ (which has numerical formulas, chemical formulas, tables, etc.), an alkoxy group having 1 to 6 carbon atoms, a group represented by CONH_2, NHR^1^0 ( (R^1^0 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (R^1^1 represents a hydrogen atom, a hydroxyl group, an amino group, or nitro group), ▲There are mathematical formulas, chemical formulas, tables, etc.▼, furyl groups, thienyl groups, or ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Groups represented by ▲Mathematical formulas, chemical formulas, tables, etc. ▼(R^1^2 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a carboxyl group), ▲Mathematical formulas, chemical formulas, tables, etc. There is a group represented by ▼, ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ Groups represented by NHCNH_2, ▲ Numerical formulas, chemical formulas, tables, etc. ▼ Groups represented by or ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ Represents a group represented by } An antibacterial agent containing a rifamycin derivative represented by the following and its salt as an active ingredient.