JP2019182831A - 抗菌活性を有するイサチンスピロ化合物およびその調製方法 - Google Patents
抗菌活性を有するイサチンスピロ化合物およびその調製方法 Download PDFInfo
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- JXDYKVIHCLTXOP-UHFFFAOYSA-N Pseudoisatin Natural products C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 title claims abstract description 22
- -1 Isatin spiro compounds Chemical class 0.000 title claims abstract description 17
- 230000000844 anti-bacterial effect Effects 0.000 title abstract description 13
- 238000000034 method Methods 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 241000894006 Bacteria Species 0.000 abstract description 8
- 230000003197 catalytic effect Effects 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 18
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 17
- 239000003729 cation exchange resin Substances 0.000 description 17
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 17
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 17
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 229920001577 copolymer Polymers 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- 125000000542 sulfonic acid group Chemical group 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 241000588724 Escherichia coli Species 0.000 description 7
- NUDGQVHENFOCFX-UHFFFAOYSA-N 1,3-diphenylpropane-1,2-dione Chemical compound C=1C=CC=CC=1C(=O)C(=O)CC1=CC=CC=C1 NUDGQVHENFOCFX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229940118019 malondialdehyde Drugs 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- HCSDAMGBOVWGEO-UHFFFAOYSA-N 3-oxo-3-phenylpropanal Chemical compound O=CCC(=O)C1=CC=CC=C1 HCSDAMGBOVWGEO-UHFFFAOYSA-N 0.000 description 4
- MBVCESWADCIXJN-UHFFFAOYSA-N 5-Bromoisatin Chemical compound BrC1=CC=C2NC(=O)C(=O)C2=C1 MBVCESWADCIXJN-UHFFFAOYSA-N 0.000 description 4
- XHDJYQWGFIBCEP-UHFFFAOYSA-N 5-Chloro-1H-indole-2,3-dione Chemical compound ClC1=CC=C2NC(=O)C(=O)C2=C1 XHDJYQWGFIBCEP-UHFFFAOYSA-N 0.000 description 4
- OCVKSIWBTJCXPV-UHFFFAOYSA-N 7-bromo-1h-indole-2,3-dione Chemical compound BrC1=CC=CC2=C1NC(=O)C2=O OCVKSIWBTJCXPV-UHFFFAOYSA-N 0.000 description 4
- MPLXQMMMGDYXIT-UHFFFAOYSA-N 7-chloro-1h-indole-2,3-dione Chemical compound ClC1=CC=CC2=C1NC(=O)C2=O MPLXQMMMGDYXIT-UHFFFAOYSA-N 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 4
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- BHYQZAICFZVNAR-LBPRGKRZSA-N (3R)-7-chloro-1-methyl-2-oxospiro[indole-3,2'-oxete]-3'-carbaldehyde Chemical compound ClC=1C=CC=C2C=1N(C([C@@]21OC=C1C=O)=O)C BHYQZAICFZVNAR-LBPRGKRZSA-N 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
- 241001360526 Escherichia coli ATCC 25922 Species 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 229940126142 compound 16 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LCYLORRUGUGXNT-XMMPIXPASA-N (3R)-3'-benzoyl-5-bromo-1-methyl-4'-phenylspiro[indole-3,2'-oxete]-2-one Chemical compound C(C1=CC=CC=C1)(=O)C=1[C@@]2(OC=1C1=CC=CC=C1)C(N(C1=CC=C(C=C12)Br)C)=O LCYLORRUGUGXNT-XMMPIXPASA-N 0.000 description 1
- LROONUDUGOFCPL-ZDUSSCGKSA-N (3R)-5-bromo-1-ethyl-2-oxospiro[indole-3,2'-oxete]-3'-carbaldehyde Chemical compound BrC=1C=C2C(=CC=1)N(C([C@@]21OC=C1C=O)=O)CC LROONUDUGOFCPL-ZDUSSCGKSA-N 0.000 description 1
- RNRZNZWPCURWLU-LBPRGKRZSA-N (3R)-5-bromo-1-methyl-2-oxospiro[indole-3,2'-oxete]-3'-carbaldehyde Chemical compound BrC=1C=C2C(=CC=1)N(C([C@@]21OC=C1C=O)=O)C RNRZNZWPCURWLU-LBPRGKRZSA-N 0.000 description 1
- VAHREDCGOKJVRP-LBPRGKRZSA-N (3R)-5-chloro-1-methyl-2-oxospiro[indole-3,2'-oxete]-3'-carbaldehyde Chemical compound ClC=1C=C2C(=CC=1)N(C([C@@]21OC=C1C=O)=O)C VAHREDCGOKJVRP-LBPRGKRZSA-N 0.000 description 1
- UQPRLEXEVBDWQI-LBPRGKRZSA-N (3R)-7-bromo-1-methyl-2-oxospiro[indole-3,2'-oxete]-3'-carbaldehyde Chemical compound BrC=1C=CC=C2C=1N(C([C@@]21OC=C1C=O)=O)C UQPRLEXEVBDWQI-LBPRGKRZSA-N 0.000 description 1
- BOKIMPXFRBMVPV-HXUWFJFHSA-N (3R)-7-bromo-2-oxo-4'-phenyl-1-propylspiro[indole-3,2'-oxete]-3'-carbaldehyde Chemical compound BrC=1C=CC=C2C=1N(C([C@@]21OC(=C1C=O)C1=CC=CC=C1)=O)CCC BOKIMPXFRBMVPV-HXUWFJFHSA-N 0.000 description 1
- ZIHHTTYCZKXHAY-LJQANCHMSA-N (3R)-7-chloro-1-ethyl-2-oxo-4'-phenylspiro[indole-3,2'-oxete]-3'-carbaldehyde Chemical compound C(=O)C1=C(O[C@@]11C(=O)N(CC)C2=C(Cl)C=CC=C12)C1=CC=CC=C1 ZIHHTTYCZKXHAY-LJQANCHMSA-N 0.000 description 1
- WCRNQWHDHBUPAS-ZDUSSCGKSA-N (3R)-7-chloro-1-ethyl-2-oxospiro[indole-3,2'-oxete]-3'-carbaldehyde Chemical compound ClC=1C=CC=C2C=1N(C([C@@]21OC=C1C=O)=O)CC WCRNQWHDHBUPAS-ZDUSSCGKSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Classifications
-
- 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
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
Abstract
Description
本発明は医薬品化学の分野に関し、特に抗菌活性を有するイサチンスピロ化合物およびその調製方法に関する。
一実施形態において、本発明は以下の式(I):
本発明の実施形態をここで詳細に言及する。
(1)1:1〜1.5:1〜1.2のモル比のイサチン誘導体(式(II))、脂肪アルコール(式(III))、およびジカルボニル化合物(式(IV))をリアクターに添加した。リアクターの容積の2/3未満の非極性溶媒を前記リアクターに添加し、そして前記混合物を充分に混合した。前記非極性溶媒は、ベンゼン、CCl4、トルエン、またはテトラヒドロフラン(THF)であり得る。触媒としての強酸カチオン交換樹脂、フェロセン、および酢酸パラジウムの存在下で、前記混合物を60〜100℃にて3〜7時間撹拌し加熱した。
(R)−5−ブロモ−1−メチル−2−オキソスピロ[インドリン−3,2’−オキセテ]−3’−カルボアルデヒド(化合物1)の前記調製
(R)−7−ブロモ−1−メチル−2−オキソスピロ[インドリン−3,2’−オキセテ]−3’−カルボアルデヒド(化合物2)の前記調製
(R)−5−クロロ−1−メチル−2−オキソスピロ[インドリン−3,2’−オキセテ]−3’−カルボアルデヒド(化合物3)の前記調製
(R)−7−クロロ−1−メチル−2−オキソスピロ[インドリン−3,2’−オキセテ]−3’−カルボアルデヒド(化合物4)の前記調製
(R)−3’−ベンゾイル−5−ブロモ−1−メチル−4’−フェニルスピロ[インドリン−3,2’−オキセト]−2−オン(化合物5)の前記調製
(R)−3’−ベンゾイル−7−ブロモ−1−メチル−4’−フェニルスピロ[インドリン−3,2’−オキセト]−2−オン(化合物6)の前記調製
(R)−3’−ベンゾイル−5−クロロ−1−メチル−4’−フェニルスピロ[インドリン−3,2’−オキセト]−2−オン(化合物7)の前記調製
(R)−3’−ベンゾイル−7−クロロ−1−メチル−4’−フェニルスピロ[インドリン−3,2’−オキセト]−2−オン(化合物8)の前記調製
(R)−3’−ベンゾイル−5−ブロモ−1−エチルスピロ[インドリン−3,2’−オキセト]−2−オン(化合物9)の前記調製
(R)−7−ブロモ−2−オキソ−4’−フェニル−1−プロピルスピロ[インドリン−3,2’−オキセテ]−3’−カルボアルデヒド(化合物10)の前記調製
(R)−3’−ベンゾイル−5−クロロ−1−プロピルスピロ[インドリン−3,2’−オキセト]−2−オン(化合物11)の前記調製
(R)−7−クロロ−1−エチル−2−オキソ−4’−フェニルスピロ[インドリン−3,2’−オキセテ]−3’−カルボアルデヒド(化合物12)の前記調製
(R)−5−ブロモ−1−エチル−2−オキソスピロ[インドリン−3,2’−オキセテ]−3’−カルボアルデヒド(化合物13)の前記調製
(R)−7−クロロ−1−エチル−2−オキソスピロ[インドリン−3,2’−オキセテ]−3’−カルボアルデヒド(化合物14)の前記調製
(R)−3’−ベンゾイル−7−ブロモ−4’−フェニル−1−プロピルスピロ[インドリン−3,2’−オキセト]−2−オン(化合物15)の前記調製
(R)−3’−ベンゾイル−5−クロロ−4’−フェニル−1−プロピルスピロ[インドリン−3,2’−オキセト]−2−オン(化合物16)の前記調製
前記発明の前記化合物の抗菌活性試験
Claims (5)
- 次式(I):
- R1がClまたはBrである、請求項1に記載のイサチンスピロ化合物。
- R2がメチル、エチル、プロピル、またはベンジルである、請求項1に記載のイサチンスピロ化合物。
- R3およびR3’が独立してHまたはフェニルである、請求項1に記載のイサチンスピロ化合物。
- 前記化合物が:
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