JP5068813B2 - 新規なベンゾチアジノン誘導体、及び抗菌剤としてのその使用 - Google Patents
新規なベンゾチアジノン誘導体、及び抗菌剤としてのその使用 Download PDFInfo
- Publication number
- JP5068813B2 JP5068813B2 JP2009511341A JP2009511341A JP5068813B2 JP 5068813 B2 JP5068813 B2 JP 5068813B2 JP 2009511341 A JP2009511341 A JP 2009511341A JP 2009511341 A JP2009511341 A JP 2009511341A JP 5068813 B2 JP5068813 B2 JP 5068813B2
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- JP
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- Prior art keywords
- azaspiro
- dioxa
- benzothiazin
- nitro
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229960005206 pyrazinamide Drugs 0.000 description 1
- IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- DSKFKLXCUIMBLA-UHFFFAOYSA-M sodium 1,4-dioxa-8-azaspiro[4.5]decane-8-carbodithioate dihydrate Chemical compound O.O.[Na+].[S-]C(=S)N1CCC2(CC1)OCCO2 DSKFKLXCUIMBLA-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 238000004613 tight binding model Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 239000000814 tuberculostatic agent Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
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Description
R3及びR4は、互いに独立して、H、飽和若しくは不飽和の、直鎖状若しくは分岐状の鎖構成元素数1〜7の脂肪族基、炭素数3〜6のシクロアルキル、ベンジル、SR9、又はOR9であり;
R5及びR6は、互いに独立して、飽和若しくは不飽和の、ハロゲン化若しくは非ハロゲン化された、直鎖状若しくは分岐状の鎖構成元素数1〜8の脂肪族基、炭素数3〜6のシクロアルキル、又はフェニルであるか、R5及びR6は一緒になって二価の基−(CR9 2)m−を示すか、R5及びR6は一緒になって二価の基
R7、R8及びR9は、互いに独立して、H、飽和若しくは不飽和の、ハロゲン化若しくは非ハロゲン化された、直鎖状若しくは分岐状の鎖構成元素数1〜7の脂肪族基、モノ、ジ若しくはトリフルオロメチル、ハロゲン、又はフェニルであるか、R3及びR4は一緒になって二価の基−(CH2)n−(式中、nは2〜7)を示し;
R10は、H、飽和若しくは不飽和の、ハロゲン化若しくは非ハロゲン化された、直鎖状若しくは分岐状の鎖構成元素数1〜7の脂肪族基、NO2、NR7R8、CN、CONR7R8、COOR9、CHO、ハロゲン、SO2NR7R8、SR9、OR9、OCF3、モノ、ジ若しくはトリフルオロメチル、ベンジル、又はフェニルである)の化合物を提供することによって解決する。
2−(4−R5−4−R6−ピペリジン−1−イル)−8−ニトロ−6−トリフルオロメチル−1,3−ベンゾチアジン−4−オン、
6−シアノ−2−(4−R5−4−R6−ピペリジン−1−イル)−8−ニトロ−1,3−ベンゾチアジン−4−オン、
6−アミド−2−(4−R5−4−R6−ピペリジン−1−イル)−8−ニトロ−1,3−ベンゾチアジン−4−オン、
2−(1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−R1−6−R2−1,3−ベンゾチアジン−4−オン、
2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−R1−6−R2−1,3−ベンゾチアジン−4−オン、
2−[(2R)−2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル]−8−R1−6−R2−1,3−ベンゾチアジン−4−オン、
2−[(2S)−2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル]−8−R1−6−R2−1,3−ベンゾチアジン−4−オン、
2−(2,3−ジメチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−R1−6−R2−1,3−ベンゾチアジン−4−オン、及び
2−(1,5−ジオキサ−9−アザスピロ[5.5]ウンデシ−9−イル)−8−R1−6−R2−1,3−ベンゾチアジン−4−オン(式中、R1、R2、R5及びR6は前記と同義)からなる群から選択される式(I)の化合物に関する。
2−(1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−6,8−ジニトロ−1,3−ベンゾチアジン−4−オン、
2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−6,8−ジニトロ−1,3−ベンゾチアジン−4−オン、
2−(4,4−ジエトキシピペリジン−1−イル)−6,8−ジニトロ−1,3−ベンゾチアジン−4−オン、
7−メチル−2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−6,8−ジニトロ−1,3−ベンゾチアジン−4−オン、
2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−6−(トリフルオロメチル)−1,3−ベンゾチアジン−4−オン、
2−(2,3−ジメチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−6−(トリフルオロメチル)−1,3−ベンゾチアジン−4−オン、
2−(1,5−ジオキサ−9−アザスピロ[5.5]ウンデシ−9−イル)−8−ニトロ−6−(トリフルオロメチル)−1,3−ベンゾチアジン−4−オン、
2−(1,5−ジオキサ−9−アザスピロ[5.5]ウンデシ−9−イル)−8−ニトロ−4−オキソ−1,3−ベンゾチアジン−6−カルボニトリル、
2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−4−オキソ−1,3−ベンゾチアジン−6−カルボニトリル、
8−アミノ−2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−4−オキソ−1,3−ベンゾチアジン−6−カルボニトリル、及び
8−アミノ−2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−6−(トリフルオロメチル)−1,3−ベンゾチアジン−4−オンからなる群から選択される少なくとも1種の化合物に関する。
薬剤及び溶媒は、ランカスターシンセシス(Lancaster Synthesis)(英国ランカシャー)或いはアルドリッチ(シグマ・アルドリッチ(Sigma-Aldrich)社、米国セントルイス)から購入し、精製を行わずに合成に用いた。融点は、BP手法に従って測定し、補正は行っていない(Electrothermal 9001、英国)。分析結果を元素記号のみで示す場合、分析結果は理論値の±0.3%以内である(Carlo−Erba 5500、イタリア国)。NMRスペクトルはVarian Unity Plus 400(米国)により測定した。1H NMRのTMS(δ)からの低磁場側へのシフトはppmで表わす。質量分析スペクトルは、直接注入によりFinnigan SSQ−700(米国)装置を用いて得た。反応及び化合物の純度は、Silicagel 60 F254アルミニウムシート(メルク社、ドイツ国)を用いてTLCにより制御した。
A法
25%アンモニア水(50mL)中に、攪拌下、2−クロロ−3−ニトロ−5−トリフルオロメチルベンゾイルクロリド(5g)(D.E Welch、R.R.Baron、B.A.Burton、J.Med.Chem.12;2;1969;299〜303)のアセトニトリル(10mL)溶液を−20℃で滴下した。10分後、酢酸エチル(50mL)を添加した。有機相を分離し、水で2回洗浄し、Na2SO4で乾燥し、活性炭で処理し、濾過し、減圧下濃縮した。得られた粗生成物をエタノールから晶出し精製した。2−クロロ−3−ニトロ−5−(トリフルオロメチル)ベンズアミドの収率は92%であった。融点195〜197℃(メタノール)。
詳細な手続きは、J.Imrich、P.Kristian、Coll.Czech.Chem.Commun.、47、1982、3268〜3282;D.Koscik、P.Kristian、J.Gonda、E.Dandarova、Coll.Czech.Chem.Commun.、48、1983、3315〜3328;D.Koscik、P.Kristian、O.Forgac、Coll.Czech.Chem.Commun.、48、1983、3427〜3432;T.H.Cronin、H.−J.E.Hess、米国特許第3522247号に記載の手続きと同様である。2−(1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−6−トリフルオロメチル)−1,3−ベンゾチアジン−4−オンの収率は0.21%である。この化合物は、分光分析データによれば、A法で合成した化合物と同一である。
実施例1の手続きに従った。淡黄色結晶性固体。収率54%。融点192〜3℃。
出発原料として2−ヒドロキシ−3,5−ジニトロ安息香酸を用いて実施例1の手続きに従って合成した。淡黄色結晶性固体。収率43%。融点271〜3℃(EtOH/DMF)。
出発原料として2−ヒドロキシ−3,5−ジニトロ安息香酸を用いて実施例1の手続きに従って合成した。黄色結晶性固体。収率57%。融点139〜142℃(EtOH/DMF)。
出発原料として2−ヒドロキシ−3−ニトロ−5−トリフルオロメチル安息香酸を用いて実施例1の手続きに従って合成した。淡黄色結晶性固体。収率58%。融点205〜207℃(EtOH/DMF)。
出発原料として2−ヒドロキシ−3,5−ジニトロ安息香酸を用いて実施例1の手続きに従って合成した。黄色結晶性固体。収率32%。融点179〜181℃(i−PrOH)。
出発原料として2−ヒドロキシ−3,5−ジニトロ安息香酸を用いて実施例1の手続きに従って合成した。黄色結晶性固体。収率51%。融点193〜195℃(i−PrOH/DMF)。
出発原料として2−ヒドロキシ−4−メチル−3,5−ジニトロ安息香酸を用いて実施例1の手続きに従って合成した。黄色結晶性固体。収率51%。融点207〜210℃(i−PrOH/DMF)。
2−ヒドロキシ−5−ヨード安息香酸(5g、19mmol)のDMF(50mL)溶液に、攪拌下、CuCN(I)(乾燥重量2.5g、22mmol)を少量ずつ添加した。反応液を5時間還流し、水(100mL)及び酢酸エチル(50mL)を添加した。その後、濃縮した。換気を十分に行った状態で、pHが約3になるまで塩酸を注意深く添加した。有機相を分離し、水で2回洗浄、Na2SO4で乾燥、活性炭で処理、濾過、減圧下濃縮した。得られた粗生成物を水から晶出し、精製した。5−シアノ−2−ヒドロキシ安息香酸の収率は71%であった。実施例1の手続きに従った。収率44%。融点217〜220℃(EtOH/DMF)。
実施例9の手続きに従った。黄色結晶性固体。収率34%。融点251〜253℃(EtOH/DMF)。
実施例9の手続きに従った。黄色結晶性固体。収率40%。融点230〜232℃(EtOH/DMF)。
Mycobacterium smegmatis SG987、M.aureum SB66、M.vaccae IMET 1010670及びM.fortuitum Bに対する本化合物の抗菌活性を試験した。試験は、NCCLSガイドライン[National Committee for Clinical Laboratory Standards:Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically;第5版;Villanova編;Approved standard Document M7−A5.NCCLS(2000)]に従って、ミューラー−ヒントンブロス(Difco)においてマイクロブロス希釈法によって、最小阻害濃度(MIC)を測定することにより行った。
化学療法における有効性を測定するため、本発明者らは、実験的に血中に結核菌を播種したBALB/cマウスを用いた。マウスは、ロシア医科学アカデミーの中央動物ナーサリー(Central Animal Nursery of the Russian Academy of Medical Sciences)から入手した。この研究においては、本発明者らは、隔離後、体重(20〜25g)で標準化した雄性のみのマウスを用いた。マウスは、Mycobacterium tuberculosis H37Rvで2週間ビルレント培養して感染させた。感染は、このマイコバクテリアの懸濁液を、生理食塩水(0.5mL)中のCFU(コロニー形成ユニット)が5×106個となる用量で(尾静脈に)静脈内注入して行った。実験動物は全て、使用した処置計画によって群分した。試験対象の医薬の用量は、文献からのデータ及び事前調査の結果に基づき選択した。
Claims (14)
- 式(I)
R3及びR4はHであり;
R5及びR6は、互いに独立して、飽和若しくは不飽和の、直鎖状若しくは分岐状の鎖構成元素数1〜8の脂肪族基、炭素数3〜6のシクロアルキル、又はフェニルであるか、R5及びR6は一緒になって二価の基−(CR9 2)m−を示すか、R5及びR6は一緒になって二価の基
R7、R8及びR9は、互いに独立して、H、飽和若しくは不飽和の、ハロゲン化若しくは非ハロゲン化された、直鎖状若しくは分岐状の鎖構成元素数1〜7の脂肪族基、又はフェニルであり;
R10は、H、飽和若しくは不飽和の、ハロゲン化若しくは非ハロゲン化された、直鎖状若しくは分岐状の鎖構成元素数1〜7の脂肪族基、NO2、CN、CONR7R8、COOR9、CHO、ハロゲン、SO2NR7R8、SR9、OR9、OCF3、モノ、ジ若しくはトリフルオロメチル、ベンジル、又はフェニルである)の化合物又はその塩。 - R1はNO2であり、R2はCF3であり、R3及びR4はHであり、R5及びR6は請求項1と同義である、請求項1に記載の式(I)の化合物又はその塩。
- R1はNO2であり、R2はCNであり、R3及びR4はHであり、R5及びR6は請求項1と同義である、請求項1に記載の式(I)の化合物又はその塩。
- R1及びR2はNO2であり、R3及びR4はHであり、R5及びR6は請求項1と同義である、請求項1に記載の式(I)の化合物又はその塩。
- R1はNO2であり、R2はCONH2であり、R3及びR4はHであり、R5及びR6は請求項1と同義である、請求項1に記載の式(I)の化合物又はその塩。
- R5及びR6は、互いに独立して、C1−8アルキル基である、請求項1に記載の式(I)の化合物又はその塩。
- 2−(1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−6−(トリフルオロメチル)−1,3−ベンゾチアジン−4−オン、
2−(7,12−ジオキサ−3−アザスピロ[5.6]ドデシ−3−イル)−6,8−ジニトロ−1,3−ベンゾチアジン−4−オン、
2−(1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−4−オキソ−1,3−ベンゾチアジン−6−カルボニトリル、
2−(1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−6,8−ジニトロ−1,3−ベンゾチアジン−4−オン、
2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−6,8−ジニトロ−1,3−ベンゾチアジン−4−オン、
2−(4,4−ジエトキシピペリジン−1−イル)−6,8−ジニトロ−1,3−ベンゾチアジン−4−オン、
2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−6−(トリフルオロメチル)−1,3−ベンゾチアジン−4−オン、
2−(2,3−ジメチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−6−トリフルオロメチル)−1,3−ベンゾチアジン−4−オン、
2−(1,5−ジオキサ−9−アザスピロ[5.5]ウンデシ−9−イル)−8−ニトロ−6−(トリフルオロメチル)−1,3−ベンゾチアジン−4−オン、
2−(1,5−ジオキサ−9−アザスピロ[5.5]ウンデシ−9−イル)−8−ニトロ−4−オキソ−1,3−ベンゾチアジン−6−カルボニトリル、及び
2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−4−オキソ−1,3−ベンゾチアジン−6−カルボニトリルからなる群から選択される、化合物又はその塩。 - 医薬組成物を調製するための、請求項1〜7のいずれか1項に記載の化合物又はその塩の使用。
- 哺乳類における結核感染又はハンセン病感染の治療的又は予防的処置のための医薬を調製するための、請求項1〜7のいずれか1項に記載の化合物又はその塩の使用。
- 請求項1〜7のいずれか1項に記載の化合物又はその塩を含む医薬組成物。
- 哺乳類における結核感染又はハンセン病感染の治療的又は予防的処置方法における使用のためのものである、請求項10に記載の医薬組成物。
- 2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−6−(トリフルオロメチル)−1,3−ベンゾチアジン−4−オンである化合物又はその塩。
- 2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−6−(トリフルオロメチル)−1,3−ベンゾチアジン−4−オンである化合物又はその塩を含む医薬組成物。
- 2−(2−メチル−1,4−ジオキサ−8−アザスピロ[4.5]デシ−8−イル)−8−ニトロ−6−(トリフルオロメチル)−1,3−ベンゾチアジン−4−オンである化合物又はその塩を含む、哺乳類における結核感染又はハンセン病感染の治療的又は予防的処置方法における使用のための医薬組成物。
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PL2029583T3 (pl) | 2006-05-24 | 2010-10-29 | Leibniz Inst Fuer Naturstoff Forschung Und Infektionsbiologie E V Hans Knoell Inst | Nowe pochodne benzotiazynonu i ich zastosowanie jako środków przeciwbakteryjnych |
EP2020406A1 (en) * | 2007-07-16 | 2009-02-04 | Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e.V. Hans-Knöll-Institut | New antimicrobial compounds, their synthesis and their use for treatment of mammalian infection |
EP2240777B1 (en) | 2008-02-13 | 2013-08-07 | Sentinel CH S.p.A. | An effective new drug target for the treatment of tuberculosis |
EP2380886A1 (en) | 2010-04-23 | 2011-10-26 | Vadim A. Makarov | Process for the preparation of 2-aminosubstituted 1,3-benzothiazine-4-ones |
WO2012066518A1 (en) | 2010-11-19 | 2012-05-24 | Ecole Polytechnique Federale De Lausanne (Epfl) | 2-piperazin-1-yl-4h-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections |
EP2468746A1 (en) | 2010-12-23 | 2012-06-27 | The University of Queensland | Benzothiazinone compounds and their use as anti-tuberculosis agents |
US8486717B2 (en) | 2011-01-18 | 2013-07-16 | Symbolics, Llc | Lateral flow assays using two dimensional features |
CN102276598B (zh) * | 2011-05-27 | 2014-11-05 | 四川大学 | 苯并噻嗪硫酮衍生物及其制备方法和用途 |
CN102367239B (zh) * | 2011-07-20 | 2015-10-28 | 沈阳药科大学 | 2-芳基-2,3-二氢-4h-1,3-苯并噻嗪-4-酮衍生物及其用途 |
EP2570413A1 (en) | 2011-09-15 | 2013-03-20 | The University Of Queensland | Benzothiazinone derivatives as anti-tuberculosis agents |
CN103508980B (zh) * | 2012-06-14 | 2016-07-06 | 四川大学 | 苯并噻嗪-4-酮衍生物及其制备方法和用途 |
US9874556B2 (en) | 2012-07-18 | 2018-01-23 | Symbolics, Llc | Lateral flow assays using two dimensional features |
US9599615B2 (en) | 2013-03-13 | 2017-03-21 | Symbolics, Llc | Lateral flow assays using two dimensional test and control signal readout patterns |
CN104211708B (zh) * | 2013-05-29 | 2018-08-24 | 中国医学科学院药物研究所 | 苯并噁嗪酮衍生物及其作为抗菌剂的应用 |
MY179376A (en) | 2013-11-18 | 2020-11-05 | Basf Se | Novel initiator for preparing alkanesulfonic acids from alkane and oleum |
DE102014012546A1 (de) * | 2014-09-26 | 2016-03-31 | Martin-Luther-Universität Halle-Wittenberg | Antimykobakteriell wirksame Substanzen, Verfahren zu ihrer Herstellung und deren Verwendung |
EP3072889A1 (en) | 2015-03-23 | 2016-09-28 | Ecole Polytechnique Federale De Lausanne (Epfl) | 2-Homopiperazine-1-yl-4H-1,3-benzothiazine-4-one derivatives and process for the preparation of 2-(homo)piperazine 1,3-benzothiazine-4-one hydrochlorides |
CN105622596B (zh) * | 2016-02-19 | 2018-10-30 | 浙江司太立制药股份有限公司 | 含有烷氧亚胺基氮杂环片段的苯并噻嗪-4-酮类化合物及其制备方法 |
CN105669664B (zh) * | 2016-02-19 | 2019-05-10 | 浙江司太立制药股份有限公司 | 含有碱性氮杂环片段的苯并噻嗪-4-酮类化合物及其制备方法 |
US11155542B2 (en) | 2016-09-22 | 2021-10-26 | University Of Notre Dame Du Lac | Antimicrobial compounds, their use for the treatment of mammalian infections and a new metabolic mechanism |
RU2663848C1 (ru) * | 2018-03-23 | 2018-08-10 | Федеральное государственное бюджетное учреждение науки Институт органического синтеза им. И.Я. Постовского Уральского отделения Российской академии наук (ИОС УрО РАН) | 5-Фтор-2-(4-этоксикарбонилпиперазин-1-ил)-1,3-бензотиазин-4-он, обладающий противотуберкулезной активностью |
CN111269197A (zh) * | 2020-04-08 | 2020-06-12 | 苏州大学 | 苯并噻嗪酮化合物及其制备方法与作为抗结核药物的应用 |
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