JP6820312B2 - アトルバスタチンにより増加し、炎症を消失させる新規な13−シリーズのレゾルビンの解明 - Google Patents
アトルバスタチンにより増加し、炎症を消失させる新規な13−シリーズのレゾルビンの解明 Download PDFInfo
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- JP6820312B2 JP6820312B2 JP2018502764A JP2018502764A JP6820312B2 JP 6820312 B2 JP6820312 B2 JP 6820312B2 JP 2018502764 A JP2018502764 A JP 2018502764A JP 2018502764 A JP2018502764 A JP 2018502764A JP 6820312 B2 JP6820312 B2 JP 6820312B2
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- PFTXKXWAXWAZBP-UHFFFAOYSA-N octacene Chemical compound C1=CC=CC2=CC3=CC4=CC5=CC6=CC7=CC8=CC=CC=C8C=C7C=C6C=C5C=C4C=C3C=C21 PFTXKXWAXWAZBP-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- BDOLXPFAFMNDOK-UHFFFAOYSA-N oxazaborolidine Chemical class B1CCON1 BDOLXPFAFMNDOK-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- YIYBQIKDCADOSF-UHFFFAOYSA-N pent-2-enoic acid Chemical compound CCC=CC(O)=O YIYBQIKDCADOSF-UHFFFAOYSA-N 0.000 description 1
- 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000005499 phosphonyl group Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- OIWTWACQMDFHJG-CCFUIAGSSA-N resolvin D1 Chemical compound CC\C=C/C[C@H](O)\C=C\C=C/C=C/C=C/[C@@H](O)[C@@H](O)C\C=C/CCC(O)=O OIWTWACQMDFHJG-CCFUIAGSSA-N 0.000 description 1
- JBRPFYYLEQERPG-XTIXYJHRSA-N resolvin d5 Chemical compound CC\C=C/C[C@H](O)\C=C\C=C/C\C=C/C=C/[C@@H](O)\C=C/CCCC(O)=O JBRPFYYLEQERPG-XTIXYJHRSA-N 0.000 description 1
- FMKFBRKHHLWKDB-UHFFFAOYSA-N rubicene Chemical compound C12=CC=CC=C2C2=CC=CC3=C2C1=C1C=CC=C2C4=CC=CC=C4C3=C21 FMKFBRKHHLWKDB-UHFFFAOYSA-N 0.000 description 1
- WEMQMWWWCBYPOV-UHFFFAOYSA-N s-indacene Chemical compound C=1C2=CC=CC2=CC2=CC=CC2=1 WEMQMWWWCBYPOV-UHFFFAOYSA-N 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000012066 statistical methodology Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- PGXOVVAJURGPLL-UHFFFAOYSA-N trinaphthylene Chemical group C1=CC=C2C=C3C4=CC5=CC=CC=C5C=C4C4=CC5=CC=CC=C5C=C4C3=CC2=C1 PGXOVVAJURGPLL-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000036325 urinary excretion Effects 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 235000014692 zinc oxide Nutrition 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/42—Unsaturated compounds containing hydroxy or O-metal groups
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- 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
- A61K31/40—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
-
- 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
-
- 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本出願は、2015年7月20日に出願された米国特許仮出願第62/194,485号の優先権の恩典を主張するものであり、この仮出願は引用によりその全体が本明細書に組み込まれる。
本発明は、米国立衛生研究所によって付与された助成金番号P01GM095467での政府の補助を伴ってなされた。米国政府は、本発明において一定の権利を有する。
またはその薬学的に許容され得る塩。一部の態様では、Zが−C(O)ORdである場合、ZのRdは、P1、P2およびP3がすべて水素原子である場合、水素ではない
またはその薬学的に許容され得る塩。種々の態様において、Zが−C(O)ORdである場合、ZのRdは、P1、P2およびP3がすべて水素原子である場合、水素ではない。
またはその薬学的に許容され得る塩。一部の態様では、Zが−C(O)ORdである場合、ZのRdは、P1とP2がともに水素原子である場合、水素ではない。
種々の態様において、Zが−C(O)ORdである場合、ZのRdは、P1、P2およびP3がすべて水素原子である場合、水素ではない。他の態様では、P1、P2およびP3がすべて水素原子である。他の態様では、P1、P2およびP3のうちの1つ以上が水素原子であり、Zが−C(O)ORdであり、ZのRdが水素である。
またはその薬学的に許容され得る塩。一部の態様では、Zが−C(O)ORdである場合、ZのRdは、P1、P2およびP3がすべて水素原子である場合、水素ではない。また他の態様では、Zが−C(O)ORdである場合、ZのRdは、P1、P2およびP3がすべて水素原子である場合、水素である。
またはその薬学的に許容され得る塩。種々の態様において、Zが−C(O)ORdである場合、ZのRdは、P1、P2およびP3がすべて水素原子である場合、水素ではない。また他の態様では、Zが−C(O)ORdである場合、ZのRdは、P1、P2およびP3がすべて水素原子である場合、水素である。
またはその薬学的に許容され得る塩。一部の態様では、Zが−C(O)ORdである場合、ZのRdは、P1とP2がともに水素原子である場合、水素ではない。他の態様では、Zが−C(O)ORdである場合、ZのRdは、P1とP2がともに水素原子である場合、水素である。
またはS−ニトロソグルタチオンとともにインキュベートした。20分後、インキュベーションをメタノールを用いてクエンチし、13−HDPAレベルをLC−MS−MSベースのLMメタボロリピドミクスを用いて評価した。
表6:13−シリーズのレゾルビンの構造、生合成および作用の証拠
7位と13位または8、12もしくは20位の炭素は、存在している場合、独立してR配置またはS配置であり;
Zは−C(O)ORd、−C(O)NRcRc、−C(O)H、−C(NH)NRcRc、−C(S)H、−C(S)ORd、−C(S)NRcRcまたは−CNであり;
各Raは独立して、水素、(C1〜C6)アルキル、(C3〜C8)シクロアルキル、シクロヘキシル、(C4〜C11)シクロアルキルアルキル、(C5〜C10)アリール、フェニル、(C6〜C16)アリールアルキル、ベンジル、2〜6員のヘテロアルキル、3〜8員のシクロヘテロアルキル、モルホリニル、ピペラジニル、ホモピペラジニル、ピペリジニル、4〜11員のシクロヘテロアルキルアルキル、5〜10員のヘテロアリールまたは6〜16員のヘテロアリールアルキルから選択され;
各Rcは独立して保護基またはRaであるか、あるいはまた、各Rcは、これが結合している窒素原子と一体となって、5〜8員のシクロヘテロアルキルまたはヘテロアリールを形成しており、該シクロヘテロアルキルまたはヘテロアリールは、任意選択で1個以上の同じかまたは異なるさらなるヘテロ原子を含むものであってもよく、任意選択で1つ以上の同じかまたは異なるRa基または適当なRb基で置換されていてもよく;
各Rbは独立して、=O、−ORd、(C1〜C3)ハロアルキルオキシ、−OCF3、=S、−SRd、=NRd、=NORd、−NRcRc、ハロゲン、−CF3、−CN、−NC、−OCN、−SCN、−NO、−NO2、=N2、−N3、−S(O)Rd、−S(O)2Rd、−S(O)2ORd、−S(O)NRcRc、−S(O)2NRcRc、−OS(O)Rd、−OS(O)2Rd、−OS(O)2ORd、−OS(O)2NRcRc、−C(O)Rd、−C(O)ORd、−C(O)NRcRc、−C(NH)NRcRc、−C(NRa)NRcRc、−C(NOH)Ra、−C(NOH)NRcRc、−OC(O)Rd、−OC(O)ORd、−OC(O)NRcRc、−OC(NH)NRcRc、−OC(NRa)NRcRc、−[NHC(O)]nRd、−[NRaC(O)]nRd、−[NHC(O)]nORd、−[NRaC(O)]nORd、−[NHC(O)]nNRcRc、−[NRaC(O)]nNRcRc、−[NHC(NH)]nNRcRcまたは−[NRaC(NRa)]nNRcRcから選択され;
各nは、独立して0〜3の整数であり;
各Rdは独立して保護基またはRaである)
を有する化合物またはその薬学的に許容され得る塩。
のうちの1つ以上を処置または予防するための方法であって、式:
Zは−C(O)ORd、−C(O)NRcRc、−C(O)H、−C(NH)NRcRc、−C(S)H、−C(S)ORd、−C(S)NRcRcまたは−CNであり;
各Raは独立して、水素、(C1〜C6)アルキル、(C3〜C8)シクロアルキル、シクロヘキシル、(C4〜C11)シクロアルキルアルキル、(C5〜C10)アリール、フェニル、(C6〜C16)アリールアルキル、ベンジル、2〜6員のヘテロアルキル、3〜8員のシクロヘテロアルキル、モルホリニル、ピペラジニル、ホモピペラジニル、ピペリジニル、4〜11員のシクロヘテロアルキルアルキル、5〜10員のヘテロアリールまたは6〜16員のヘテロアリールアルキルから選択され;
各Rcは独立して保護基またはRaであるか、あるいはまた、各Rcは、これが結合している窒素原子と一体となって、5〜8員のシクロヘテロアルキルまたはヘテロアリールを形成しており、該シクロヘテロアルキルまたはヘテロアリールは、任意選択で1個以上の同じかまたは異なるさらなるヘテロ原子を含むものであってもよく、任意選択で1つ以上の同じかまたは異なるRa基または適当なRb基で置換されていてもよく;
各Rbは独立して、=O、−ORd、(C1〜C3)ハロアルキルオキシ、−OCF3、=S、−SRd、=NRd、=NORd、−NRcRc、ハロゲン、−CF3、−CN、−NC、−OCN、−SCN、−NO、−NO2、=N2、−N3、−S(O)Rd、−S(O)2Rd、−S(O)2ORd、−S(O)NRcRc、−S(O)2NRcRc、−OS(O)Rd、−OS(O)2Rd、−OS(O)2ORd、−OS(O)2NRcRc、−C(O)Rd、−C(O)ORd、−C(O)NRcRc、−C(NH)NRcRc、−C(NRa)NRcRc、−C(NOH)Ra、−C(NOH)NRcRc、−OC(O)Rd、−OC(O)ORd、−OC(O)NRcRc、−OC(NH)NRcRc、−OC(NRa)NRcRc、−[NHC(O)]nRd、−[NRaC(O)]nRd、−[NHC(O)]nORd、−[NRaC(O)]nORd、−[NHC(O)]nNRcRc、−[NRaC(O)]nNRcRc、−[NHC(NH)]nNRcRcまたは−[NRaC(NRa)]nNRcRcから選択され;
各nは、独立して0〜3の整数であり;
各Rdは独立して保護基またはRaである)
を有する有効量の1種類以上の化合物またはその薬学的に許容され得る塩(ただし、Zが−C(O)ORdである場合、ZのRdは、P1、P2およびP3が各々、水素原子である場合、水素ではないものとする)を、それを必要とする対象に投与する工程を含み、それにより該疾患または病状が処置または予防されるようにする方法。
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Claims (10)
- 式:
- カルボン酸塩である、請求項1に記載の化合物またはその薬学的に許容され得る塩。
- 請求項1または2に記載の1つ以上の有効量の化合物またはその薬学的に許容され得る塩を含む、インフラマソームの活性化、糖尿病、鼻咽頭炎、関節痛、下痢、四肢痛、細菌感染、消化不良、悪心、筋骨格系疼痛、筋痙攣、筋肉痛、不眠症、咽喉頭痛、炎症、組織の変性、動脈の炎症、関節炎、乾癬、蕁麻疹、血管炎、喘息、眼の炎症、肺の炎症、肺線維症、脂漏性皮膚炎、膿疱性皮膚病、心血管疾患、好中球、白血球および/またはサイトカインの動員、アレルギー、アルツハイマー病、喘息、アテローム性動脈硬化、がん、心血管疾患、糖尿病、泌尿生殖器科系の障害、高血圧、感染性疾患、神経筋障害、腎障害、経口感染、または歯周病を治療または予防する薬剤。
- 請求項1または2に記載の1つ以上の有効量の化合物またはその薬学的に許容され得る塩、および担体を含む組成物。
- インフラマソームの活性化、糖尿病、鼻咽頭炎、関節痛、下痢、四肢痛、細菌感染、消化不良、悪心、筋骨格系疼痛、筋痙攣、筋肉痛、不眠症、咽喉頭痛、炎症、動脈の炎症、関節炎、乾癬、蕁麻疹、血管炎、喘息、眼の炎症、肺の炎症、肺線維症、脂漏性皮膚炎、膿疱性皮膚病、心血管疾患、好中球、白血球および/またはサイトカインの動員、アレルギー、アルツハイマー病、喘息、アテローム性動脈硬化、がん、心血管疾患、糖尿病、泌尿生殖器科系の障害、高血圧、感染性疾患、神経筋障害、腎障害、経口感染、及び歯周病のうちの1つ以上を治療または予防するための、請求項4に記載の組成物。
- 請求項1または2に記載の化合物またはその薬学的に許容され得る塩とスタチン化合物を投与することを含む、細菌感染を処置または予防するための薬剤。
- 請求項1または2に記載の化合物またはその薬学的に許容され得る塩の1つ以上を含む、スタチン療法を増強するための薬剤であって、前記薬剤がスタチン療法によって処置される対象に投与される薬剤。
- 請求項1または2に記載の化合物またはその薬学的に許容され得る塩の1つ以上を含む、細菌感染症に罹患している対象の生存率を増加させるための薬剤。
- 請求項1または2に記載の化合物またはその薬学的に許容され得る塩の1つ以上を含む、食作用、エフェロサイトーシス、創傷治癒、または組織再生を促進するための薬剤。
- 請求項1または2に記載の化合物またはその薬学的に許容され得る塩の1つ以上を含む、白血球における活性酸素種の生成を刺激するための薬剤。
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