JP2021522167A - ボロン酸誘導体およびその治療的使用 - Google Patents
ボロン酸誘導体およびその治療的使用 Download PDFInfo
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- JP2021522167A JP2021522167A JP2020557178A JP2020557178A JP2021522167A JP 2021522167 A JP2021522167 A JP 2021522167A JP 2020557178 A JP2020557178 A JP 2020557178A JP 2020557178 A JP2020557178 A JP 2020557178A JP 2021522167 A JP2021522167 A JP 2021522167A
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- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 150000004794 vinyl magnesium halides Chemical class 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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- A—HUMAN NECESSITIES
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
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- A—HUMAN NECESSITIES
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
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- A—HUMAN NECESSITIES
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- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
- A61K31/431—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- 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
- A61K31/542—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 heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
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- A61K31/542—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 heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
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- A—HUMAN NECESSITIES
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
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- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/04—Esters of boric acids
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
Description
本出願は、その全体が参照により組み込まれている、「BORONIC ACID DERIVATIVES AND THERAPEUTIC USES THEREOF」と題する2018年4月20日出願の米国仮特許出願第62/660729号の利益を主張する。
発明の分野
本発明は、化学および医薬の分野に関する。より詳細には、本発明は、ボロン酸抗菌性化合物、組成物、それらの調製、および治療剤としてのそれらの使用に関する。
抗生物質は、過去半世紀の間、感染症の処置に有効な手段である。抗生物質による治療法の開発から1980年代後半に至るまで、先進国では、細菌感染症に対する管理は、ほとんど完全であった。しかし、抗生物質の使用の圧力に反応して、多数の耐性機構が広がり、抗細菌治療法の臨床的有用性が脅かされている。抗生物質耐性株の増加は、特に、大きな病院および介護センターにおいて一般的となってきた。耐性株の増加の結果には、罹患率および致死率の一層の高まり、患者の入院の長期化、および処置費用の増大が挙げられる。
したがって、改善されたβ−ラクタマーゼ阻害剤が必要とされている。
定義
の構造を有する。
を有することを意味する。
を有することを意味する。
調製方法
式Iの化合物の合成
スキーム1
スキーム2
スキーム3
スキーム4
スキーム5
スキーム6
スキーム7
スキーム8
スキーム9
スキーム10
スキーム11
処置方法
症例
本明細書に記載されている環式ボロン酸エステル誘導体の調製に使用される物質は、公知の方法により作製され得るか、または市販されている。本明細書において特許請求されている化合物に関連する前駆体および官能基を調製する方法は、それらのそれぞれの全体が参照により組み込まれている、例えば、US7271186およびWO2009064414に記載されている手順を含めた文献に一般に記載されていることは当業者に明白であろう。これらの反応では、当業者にとってそれ自体公知であるが、一層詳細に明記されていない変形を使用することがやはり可能である。文献および本開示が示された当業者は、いずれの化合物を調製することも十分に身につけている。
(実施例1)
2−ヒドロキシ−4−(ヒドロキシメチル)−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸(化合物1)
工程2:1Cの合成
工程3:1Dの合成
工程4:1Eの合成
工程5:1Fの合成
工程6:1Gの合成
工程7:1Hの合成
工程8:1Iの合成
工程9:1の合成
LC−MS:221 [M−H]−
4−(ベンジルオキシメチル)−2−ヒドロキシ−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸の二ナトリウム塩(化合物2)
工程2:2Cの合成
工程3:2Dの合成
工程4:2Eの合成
工程5:2Fの合成
工程6:2の合成
LC−MS:343 [M+H]+
2−ヒドロキシ−4−(ヒドロキシメチル)−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸(化合物3)
LC−MS:253 [M+H]+
(4R)−2−ヒドロキシ−4−(ヒドロキシメチル)−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸および(4S)−2−ヒドロキシ−4−(ヒドロキシメチル)−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸(化合物4および5)
化合物4:
LC−MS:251 [M−H]−
LC−MS:251 [M−H]−
7−フルオロ−2−ヒドロキシ−4−(ヒドロキシメチル)−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸
(化合物6)
工程2:化合物6Bの合成
工程3:化合物6Cの合成
工程4:化合物6Dの合成
工程5:化合物6Eの合成
工程6:化合物6の合成
LC−MS:282 [M+MeCN+H]+;239 [M−H]−
(4R)−7−フルオロ−2−ヒドロキシ−4−(ヒドロキシメチル)−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸および(4S)−7−フルオロ−2−ヒドロキシ−4−(ヒドロキシメチル)−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸(化合物7および8)
化合物7:
LC−MS:239 [M−H]−
LC−MS:239[M−H]−
2−ヒドロキシ−4−(ヒドロキシメチル)−3,4−ジヒドロオキサボリニノ[6,5−c]ピリジン−8−カルボン酸
(化合物9)
工程2:化合物9Cの合成
工程3:化合物9Dの合成
工程4:化合物9の合成
LC−MS:224 [M+H]+
4−(ベンジルオキシメチル)−2−ヒドロキシ−3,4−ジヒドロオキサボリニノ[6,5−c]ピリジン−8−カルボン酸(化合物10)二ナトリウム塩
工程2:化合物10の合成
LC−MS:314 [M+H]+
2−ヒドロキシ−7−メトキシ−4−(メトキシメチル)−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸(化合物11)
工程2:化合物11Bの合成
工程3:化合物11Cの合成
工程2:化合物11の合成
LC−MS:267 [M+H]+
2−ヒドロキシ−4−(2−ヒドロキシエチル)−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸(化合物12)
工程2:化合物12Cの合成
工程3:化合物12Dの合成
工程4:化合物12Eおよび12Fの合成
工程5:化合物12の合成
LC−MS:267.2 [M+1]+
2−ヒドロキシ−4−(ヒドロキシメチル)−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸(化合物3)
工程2:化合物3Dの合成
工程3:化合物3Eの合成
工程4:化合物3Fの合成
工程5:化合物3Gの合成
工程6:化合物3の合成
LC−MS:253 [M+H]+
4−(ホルムアミドメチル)−2−ヒドロキシ−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸の二ナトリウム塩(化合物13)
工程2:化合物13Bの合成
工程3:化合物13Cの合成
工程4:化合物13Dの合成
工程5:化合物13の合成
LC−MS:280 [M+H]+;278 [M−H]−
4−(アミノメチル)−2−ヒドロキシ−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸の二ナトリウム塩(化合物14)
LC−MS:252 [M+H]+
4−(アジドメチル)−2−ヒドロキシ−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸の二ナトリウム塩(化合物15)
LC−MS:278 [M+H]+、555 [2M+H]+および535 [2M−H]−
2−ヒドロキシ−4−[[4−(ヒドロキシメチル)トリアゾール−1−イル]メチル]−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸の二ナトリウム塩(化合物16)
工程2:化合物16の合成
LC−MS:334 [M+H]+
4−(アセトアミドメチル)−2−ヒドロキシ−7−メトキシ−3,4−ジヒドロ−1,2−ベンゾオキサボリニン−8−カルボン酸の二ナトリウム塩(化合物17)
工程2:化合物17の合成
LC−MS:294 [M+H]+、292 [M−H]−
アズトレオナムの増強
表1.クラスAおよびクラスCの酵素を発現する株に対してアズトレオナムを増強するBLIの活性
Y = 5 μg/mL < MPC@4 ≦ 20 μg/mL
Z = MPC@4 > 20 μg/mL
(実施例18)
チゲモナムの増強
表2.クラスAおよびクラスCの酵素を発現する株に対してチゲモナムを増強するBLIの活性
Y = 5 μg/mL < MPC@4 ≦ 20 μg/mL
Z = MPC@4 > 20 μg/mL
(実施例19)
ビアペネムの増強
表3.クラスA(KPC)、クラスD(OXA-48)およびクラスB(NDM-1およびVIM-1)カルバペネマーゼを発現する株に対してビアペネムを増強するBLIの活性
Y = 5 μg/mL < MPC@1 ≦ 20 μg/mL
Z = MPC@1 > 20 μg/mL
(実施例20)
メロペネムの増強
表4. Acinetobacter baumanniiに由来するクラスDのカルバペネマーゼを発現する株に対してメロペネムを増強するBLIの活性
Y = 5 μg/mL < MPC@1 ≦ 20 μg/mL
Z = MPC@1 > 20 μg/mL
Claims (33)
- 式(I)もしくは式(II):
Gは、−OR1 −C(O)R1、−C(O)(CH2)0−3SR1、−C(O)(CH2)1−3R1、−C(O)OR1、−C(O)NR1R2、−C(O)NR1OR2、−N3、−NR1R2、−NR1C(O)R2、−NR1C(O)NR2R3、−NR1C(O)OR2、−NR1S(O)2R2、−NR1S(O)2NR2R3、−C(=NR1)R2、−C(=NR1)NR2R3、−NR1CR2(=NR3)、−NR1C(=NR2)NR3R4、−S(O)2R1、必要に応じて置換されているC1〜10アルキル、必要に応じて置換されているC2〜10アルケニル、必要に応じて置換されているC2〜10アルキニル、必要に応じて置換されているC3〜7カルボシクリル、必要に応じて置換されている5〜10員ヘテロシクリル、必要に応じて置換されているC6〜10アリール、必要に応じて置換されている5〜10員ヘテロアリール、必要に応じて置換されているC3〜7カルボシクリル−C1〜6アルキル、必要に応じて置換されている5〜10員ヘテロシクリル−C1〜6アルキル、必要に応じて置換されているC6〜10アリール−C1〜6アルキルおよび必要に応じて置換されている5〜10員ヘテロアリール−C1〜6アルキルからなる群から選択され、
R1、R2、R3およびR4は、それぞれ独立して、−H、必要に応じて置換されているC1〜4アルキル、必要に応じて置換されているC3〜7カルボシクリル、必要に応じて置換されている4〜10員ヘテロシクリル、必要に応じて置換されているC6〜10アリール、必要に応じて置換されているC6〜10アリール−C1〜6アルキルおよび必要に応じて置換されている5〜10員ヘテロアリールからなる群から選択され、
Jは、CR5およびNからなる群から選択され、
Lは、CR6およびNからなる群から選択され、
Mは、CR7およびNからなる群から選択され、
R5、R6およびR7は、それぞれ独立して、−H、−OR8、ハロゲン、−CF3、必要に応じて置換されているC2〜C6アルケニル、必要に応じて置換されているC2〜C6アルキニル、必要に応じて置換されているC1〜C6ヘテロアルキル、必要に応じて置換されているC3〜C7カルボシクリル、必要に応じて置換されている5〜10員ヘテロシクリル、必要に応じて置換されているC6〜10アリール、必要に応じて置換されている5〜10員ヘテロアリール、シアノ、C1〜C6アルコキシ(C1〜C6)アルキル、アリールオキシおよびスルフヒドリル(メルカプト)からなる群から選択され、
R8は、水素、必要に応じて置換されているC1〜4アルキル、必要に応じて置換されているC3〜7カルボシクリル、必要に応じて置換されている4〜10員ヘテロシクリル、必要に応じて置換されているC6〜10アリールおよび必要に応じて置換されている5〜10員ヘテロアリールからなる群から選択され、
Rは、−H、−C1〜9アルキル、−CR9R10OC(O)C1〜9アルキル、−CR9R10OC(O)OC1〜9アルキル、−CR9R10OC(O)C6〜10アリール、−CR9R10OC(O)OC6〜10アリール、
R9およびR10は、−H、必要に応じて置換されているC1〜4アルキル、必要に応じて置換されているC3〜7カルボシクリル、必要に応じて置換されている5〜10員ヘテロシクリル、必要に応じて置換されているC6〜10アリールおよび必要に応じて置換されている5〜10員ヘテロアリールからなる群から独立して選択される、
化合物または薬学的に許容されるその塩。 - Gが、−OR1、N3、−NR1R2、NR1C(O)R2、必要に応じて置換されているC1〜4アルキルおよび必要に応じて置換されている5〜10員ヘテロアリールからなる群から選択される、請求項1から4のいずれか一項に記載の化合物。
- Gが−OR1である、請求項1から5のいずれか一項に記載の化合物。
- Gが、−OHおよび−OBnからなる群から選択される、請求項1から7のいずれか一項に記載の化合物。
- Gが−OHである、請求項1から8のいずれか一項に記載の化合物。
- Mが、CR7であり、R7が、−H、−OR8およびハロゲンからなる群から選択される、請求項1から9のいずれか一項に記載の化合物。
- R8が、必要に応じて置換されているC1〜4アルキルである、請求項10に記載の化合物。
- Mが、−CH、−COMe、CFおよびNからなる群から選択される、請求項1から9のいずれか一項に記載の化合物。
- Mが−COMeである、請求項1から12のいずれか一項に記載の化合物。
- Rが−Hである、請求項1から13のいずれか一項に記載の化合物。
- 治療有効量の請求項1から15のいずれか一項に記載の化合物および薬学的に許容される賦形剤を含む、医薬組成物。
- 追加の医薬をさらに含む、請求項16に記載の医薬組成物。
- 前記追加の医薬が、抗細菌剤、抗真菌剤、抗ウイルス剤、抗炎症剤および抗アレルギー剤からなる群から選択される、請求項17に記載の組成物。
- 前記追加の医薬がβ−ラクタム抗細菌剤である、請求項18に記載の組成物。
- 前記β−ラクタム抗細菌剤が、アモキシシリン、アンピシリン(ピバンピシリン、ヘタシリン、バカンピシリン、メタムピシリン、タランピシリン)、エピシリン、カルベニシリン(カリンダシリン)、チカルシリン、テモシリン、アズロシリン、ピペラシリン、メズロシリン、メシリナム(ピブメシリナム)、スルベニシリン、ベンジルペニシリン(G)、クロメトシリン、ベンザチンベンジルペニシリン、プロカインベンジルペニシリン、アジドシリン、ペナメシリン、フェノキシメチルペニシリン(V)、プロピシリン、ベンザチンフェノキシメチルペニシリン、フェネチシリン、クロキサシリン(ジクロキサシリン、フルクロキサシリン)、オキサシリン、メチシリン、ナフシリン、ファロペネム、トモペネム、ラズペネム、セファゾリン、セファセトリル、セファドロキシル、セファレキシン、セファログリシン、セファロニウム、セファロリジン、セファロチン、セファピリン、セファトリジン、セファゼドン、セファザフル、セフラジン、セフロキサジン、セフテゾール、セファクロル、セファマンドール、セフミノクス、セフォニシド、セフォラニド、セフォチアム、セフプロジル、セフブペラゾン、セフロキシム、セフゾナム、セホキシチン、セフォテタン、セフメタゾール、ロラカルベフ、セフィキシム、セフトリアキソン、セフカペン、セフダロキシム、セフジニル、セフジトレン、セフェタメト、セフメノキシム、セフォジジム、セフォペラゾン、セフォタキシム、セフピミゾール、セフピラミド、セフポドキシム、セフスロジン、セフテラム、セフチブテン、セフチオレン、セフチゾキシム、フロモキセフ、ラタモキセフ、セフェピム、セフォゾプラン、セフピロム、セフキノム、セフトビプロール、セフタロリン、CXA−101、RWJ−54428、MC−04,546、ME1036、セフティオフール、セフキノム、セフォベシン、RWJ−442831、RWJ−333441およびRWJ−333442からなる群から選択される、請求項19に記載の組成物。
- 前記β−ラクタム抗細菌剤が、セフタジジム、ビアペネム、ドリペネム、エルタペネム、イミペネム、メロペネム、テビペネム、テビペネムピボキシル、アパペネムおよびパニペネムからなる群から選択される、請求項19に記載の組成物。
- 前記β−ラクタム抗細菌剤が、アズトレオナム、チゲモナム、BAL30072、SYN2416またはカルモナムから選択される、請求項19に記載の組成物。
- 細菌感染を処置する方法であって、それを必要とする対象に、請求項1から15のいずれか一項に記載の化合物の1種または複数種を投与するステップを含む、方法。
- 前記対象に追加の医薬を投与するステップをさらに含む、請求項23に記載の方法。
- 前記追加の医薬が、抗細菌剤、抗真菌剤、抗ウイルス剤、抗炎症剤および抗アレルギー剤からなる群から選択される、請求項24に記載の方法。
- 前記追加の医薬がβ−ラクタム抗細菌剤である、請求項25に記載の方法。
- 前記β−ラクタム抗細菌剤が、アモキシシリン、アンピシリン(ピバンピシリン、へタシリン、バカンピシリン、メタムピシリン、タランピシリン)、エピシリン、カルベニシリン(カリンダシリン)、チカルシリン、テモシリン、アズロシリン、ピペラシリン、メズロシリン、メシリナム(ピブメシリナム)、スルベニシリン、ベンジルペニシリン(G)、クロメトシリン、ベンザチンベンジルペニシリン、プロカインベンジルペニシリン、アジドシリン、ペナメシリン、フェノキシメチルペニシリン(V)、プロピシリン、ベンザチンフェノキシメチルペニシリン、フェネチシリン、クロキサシリン(ジクロキサシリン、フルクロキサシリン)、オキサシリン、メチシリン、ナフシリン、ファロペネム、トモペネム、ラズペネム、セファゾリン、セファセトリル、セファドロキシル、セファレキシン、セファログリシン、セファロニウム、セファロリジン、セファロチン、セファピリン、セファトリジン、セファゼドン、セファザフル、セフラジン、セフロキサジン、セフテゾール、セファクロル、セファマンドール、セフミノクス、セフォニシド、セフォラニド、セフォチアム、セフプロジル、セフブペラゾン、セフロキシム、セフゾナム、セホキシチン、セフォテタン、セフメタゾール、ロラカルベフ、セフィキシム、セフトリアキソン、セフカペン、セフダロキシム、セフジニル、セフジトレン、セフェタメト、セフメノキシム、セフォジジム、セフォペラゾン、セフォタキシム、セフピミゾール、セフピラミド、セフポドキシム、セフスロジン、セフテラム、セフチブテン、セフチオレン、セフチゾキシム、フロモキセフ、ラタモキセフ、セフェピム、セフォゾプラン、セフピロム、セフキノム、セフトビプロール、セフタロリン、CXA−101、RWJ−54428、MC−04,546、ME1036、セフティオフール、セフキノム、セフォベシン、RWJ−442831、RWJ−333441およびRWJ−333442からなる群から選択される、請求項26に記載の方法。
- 前記β−ラクタム抗細菌剤が、セフタジジム、ビアペネム、ドリペネム、エルタペネム、イミペネム、メロペネム、テビペネム、テビペネムピボキシル、アパペネムおよびパニペネムからなる群から選択される、請求項26に記載の方法。
- 前記β−ラクタム抗細菌剤が、アズトレオナム、チゲモナム、BAL30072、SYN2416およびカルモナムからなる群から選択される、請求項26に記載の方法。
- 前記対象が哺乳動物である、請求項23から29のいずれか一項に記載の方法。
- 前記哺乳動物がヒトである、請求項30に記載の方法。
- 前記感染が、Pseudomonas acidovorans、Pseudomonas alcaligenes、Pseudomonas putida、Burkholderia cepacia、Aeromonas hydrophilia、Francisella tularensis、Morganella morganii、Proteus mirabilis、Proteus vulgaris、Providencia alcalifaciens、Providencia rettgeri、Providencia stuartii、Acinetobacter baumannii、Bordetella pertussis、Bordetella para pertussis、Bordetella bronchiseptica、Haemophilus ducreyi、Pasteurella multocida、Pasteurella haemolytica、Branhamella catarrhalis、Borrelia burgdorferi、Kingella、Gardnerella vaginalis、Bacteroides distasonis、Bacteroides 3452A homology group、Clostridium difficile、Mycobacterium tuberculosis、Mycobacterium avium、Mycobacterium intracellulare、Mycobacterium leprae、Corynebacterium diphtheriae、Corynebacterium ulcerans、Streptococcus pneumoniae、Streptococcus agalactiae、Streptococcus pyogenes、Enterococcus faecalis、Enterococcus faecium、Staphylococcus aureus、Staphylococcus epidermidis、Staphylococcus saprophyticus、Staphylococcus intermedius、Staphylococcus hyicus subsp. hyicus、Staphylococcus haemolyticus、Staphylococcus hominisおよびStaphylococcus saccharolyticusからなる群から選択される細菌を含む、請求項23から31のいずれか一項に記載の方法。
- 前記感染が、Pseudomonas aeruginosa、Pseudomonas fluorescens、Stenotrophomonas maltophilia、Escherichia coli、Citrobacter freundii、Salmonella typhimurium、Salmonella typhi、Salmonella paratyphi、Salmonella enteritidis、Shigella dysenteriae、Shigella flexneri、Shigella sonnei、Enterobacter cloacae、Enterobacter aerogenes、Klebsiella pneumoniae、Klebsiella oxytoca、Serratia marcescens、Acinetobacter calcoaceticus、Acinetobacter haemolyticus、Yersinia enterocolitica、Yersinia pestis、Yersinia pseudotuberculosis、Yersinia intermedia、Haemophilus influenzae、Haemophilus parainfluenzae、Haemophilus haemolyticus、Haemophilus parahaemolyticus、Helicobacter pylori、Campylobacter fetus、Campylobacter jejuni、Campylobacter coli、Vibrio cholerae、Vibrio parahaemolyticus、Legionella pneumophila、Listeria monocytogenes、Neisseria gonorrhoeae、Neisseria meningitidis、Moraxella、Bacteroides fragilis、Bacteroides vulgatus、Bacteroides ovalus、Bacteroides thetaiotaomicron、Bacteroides uniformis、Bacteroides eggerthiiおよびBacteroides splanchnicusからなる群から選択される細菌を含む、請求項23から31のいずれか一項に記載の方法。
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