JP7456990B2 - 皮膚障害及び状態を予防又は治療するための方法 - Google Patents
皮膚障害及び状態を予防又は治療するための方法 Download PDFInfo
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- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 239000008136 water-miscible vehicle Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 229940045860 white wax Drugs 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
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- 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
- A61K31/403—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 carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A—HUMAN NECESSITIES
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- 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
- A61K31/435—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
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
- A61K8/492—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cosmetics (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
R1及びR2は、それぞれ独立して、H、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC1-C5アルコキシ、直鎖又は分岐したC1-C5アシル、C5-C15アリール、及びC3-C7ヘテロアリールからなる群から選択され、それらのそれぞれは、ハロゲン化物、ヒドロキシ、エステル、エーテル、C5-C15アリール、C3-C7ヘテロアリール、及びアミドの少なくとも1つで任意に置換されている。又はR1及びR2は、それらが結合している窒素原子とともに、N、O、NH、C=N、C=O及びSO2の少なくとも1つを任意に含んでもよく、かつ、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、ハロゲン化物及びシアノのうちの少なくとも1つで任意に置換されてもよい4~7員の飽和、不飽和又は芳香環を形成する。
R1及びR2は、それぞれ独立して、H、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC1-C5アルコキシ、直鎖又は分岐したC1-C5アシル、C5-C15アリール、及びC3-C7ヘテロアリールからなる群から選択され、それらのそれぞれは、ハロゲン化物、ヒドロキシ、エステル、エーテル、C5-C15アリール、C3-C7ヘテロアリール、及びアミドの少なくとも1つで任意に置換される。又はR1及びR2は、それらが結合している窒素原子とともに、N、O、NH、C=N、C=O及びSO2及びの少なくとも1つを任意に含んでもよく、かつ、直鎖又は分枝C1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、ハロゲン化物及びシアノのうちの少なくとも1つで任意に置換されてもよい4~7員の飽和、不飽和または芳香環を形成する。
Claims (16)
- 有効量のカゼインキナーゼ1阻害剤を含む、それを必要とする対象の皮膚の障害、疾患、又は状態を予防、改善又は治療するために使用される組成物であって、前記カゼインキナーゼ1阻害剤が、CKI7、D4476、IC261、式Iで表される化合物:
R1及びR2は、それぞれ独立して、H、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC1-C5アルコキシ、直鎖又は分岐したC1-C5アシル、C5-C15アリール、及びC3-C7ヘテロアリールからなる群から選択され、それぞれは、ハロゲン化物、ヒドロキシ、エステル、エーテル、C5-C15アリール、C3-C7ヘテロアリール、及びアミドの少なくとも1つで任意に置換され;あるいは、R1及びR2は、それらが結合している窒素原子とともに、N、O、NH、C=N、C=O及びSO2の少なくとも1つを任意に含み、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、ハロゲン化物及びシアノの少なくとも1つで任意に置換されてもよい4~7員の飽和、不飽和または芳香環を形成し;
R3及びR4は、それぞれ独立して、H;それらは、必要に応じてハロゲン化物、ヒドロキシ、アルコキシ、C5-C15アリール、C3-C7ヘテロアリール、エステル及びアミドの少なくとも1つで任意に置換された直鎖又は分岐したC1-C8アルキルからなる群から選択され;又は
R1又はR2は、R3とそれらがそれぞれ結合している炭素原子及び窒素原子とともに、N、NH、O、C=N、C=O、及びSO2の少なくとも1つで任意に含み、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、カルボニル、及びハロゲン化物の少なくとも1つで任意に置換されてもよい、4~7員の飽和、不飽和又は芳香環を形成し;
R5及びR8は、それぞれ独立して、H、ハロゲン化物;少なくとも1個のハロゲン化物で任意に置換される、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、及び直鎖又は分岐したC2-C8アルキニルからなる群から選択され;
R6は、直鎖又は分岐したC1-C8アルキル、C3-C7シクロアルキル、4~6員複素環、C5-C15アリール、C3-C7ヘテロアリール、ハロゲン化物、ヒドロキシ、及びC1-C5アルキルハロゲン化物の少なくとも1つで任意に置換される、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、直鎖又は分岐したC2-C8アルキニル、C5-C10シクロアルキル、及び飽和又は不飽和4~6員複素環からなる群から選択され;
R7は、C3-C7シクロアルキル、4~6員の複素環、C5-C15アリール、C3-C7ヘテロアリール、ハロゲン化物、ヒドロキシ、及びC1-C5アルキルハロゲン化物の少なくとも1つで任意に置換される直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、及び直鎖又は分岐したC2-C8アルキニルからなる群から選択される)、
式IIで表される化合物、式IIIで表される化合物、式IVで表される化合物、式Vで表される化合物及び式VIで表される化合物:
(III)、
(IV)、
(V)、
(VI)
からなる群から選択され、
前記カゼインキナーゼ1阻害剤は、前記対象に局所投与され、
前記皮膚の障害、疾患、又は状態は、UVの過剰曝露により引き起こされる、組成物。 - 前記皮膚の障害、疾患、又は状態は、日光性紅斑、日光性アレルギー、日光性蕁麻疹、日光弾性線維症、光老化、日焼け、急性日焼け、皮膚癌、日光性角化症、非定型ほくろ(atypical mole)、又はそれらの任意の組み合わせである、請求項1に記載の組成物。
- 前記皮膚癌は、基底細胞癌、メラノーマ、メルケル細胞癌、扁平上皮癌、皮膚悪性メラノーマ、又はそれらの任意の組み合わせである、請求項2に記載の組成物。
- 有効量のカゼインキナーゼ1阻害剤を含む、それを必要とする対象の皮膚の障害、疾患、又は状態を予防、改善又は治療するために使用される組成物であって、前記カゼインキナーゼ1阻害剤が、CKI7、D4476、IC261、式Iで表される化合物:
R 1 及びR 2 は、それぞれ独立して、H、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC1-C5アルコキシ、直鎖又は分岐したC1-C5アシル、C5-C15アリール、及びC3-C7ヘテロアリールからなる群から選択され、それぞれは、ハロゲン化物、ヒドロキシ、エステル、エーテル、C5-C15アリール、C3-C7ヘテロアリール、及びアミドの少なくとも1つで任意に置換され;あるいは、R 1 及びR 2 は、それらが結合している窒素原子とともに、N、O、NH、C=N、C=O及びSO 2 の少なくとも1つを任意に含み、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、ハロゲン化物及びシアノの少なくとも1つで任意に置換されてもよい4~7員の飽和、不飽和または芳香環を形成し;
R 3 及びR 4 は、それぞれ独立して、H;それらは、必要に応じてハロゲン化物、ヒドロキシ、アルコキシ、C5-C15アリール、C3-C7ヘテロアリール、エステル及びアミドの少なくとも1つで任意に置換された直鎖又は分岐したC1-C8アルキルからなる群から選択され;又は
R 1 又はR 2 は、R 3 とそれらがそれぞれ結合している炭素原子及び窒素原子とともに、N、NH、O、C=N、C=O、及びSO 2 の少なくとも1つで任意に含み、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、カルボニル、及びハロゲン化物の少なくとも1つで任意に置換されてもよい、4~7員の飽和、不飽和又は芳香環を形成し;
R 5 及びR 8 は、それぞれ独立して、H、ハロゲン化物;少なくとも1個のハロゲン化物で任意に置換される、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、及び直鎖又は分岐したC2-C8アルキニルからなる群から選択され;
R 6 は、直鎖又は分岐したC1-C8アルキル、C3-C7シクロアルキル、4~6員複素環、C5-C15アリール、C3-C7ヘテロアリール、ハロゲン化物、ヒドロキシ、及びC1-C5アルキルハロゲン化物の少なくとも1つで任意に置換される、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、直鎖又は分岐したC2-C8アルキニル、C5-C10シクロアルキル、及び飽和又は不飽和4~6員複素環からなる群から選択され;
R 7 は、C3-C7シクロアルキル、4~6員の複素環、C5-C15アリール、C3-C7ヘテロアリール、ハロゲン化物、ヒドロキシ、及びC1-C5アルキルハロゲン化物の少なくとも1つで任意に置換される直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、及び直鎖又は分岐したC2-C8アルキニルからなる群から選択される)、
式IIで表される化合物、式IIIで表される化合物、式IVで表される化合物、式Vで表される化合物及び式VIで表される化合物:
(III)、
(IV)、
(V)、
(VI)
からなる群から選択され、
前記カゼインキナーゼ1阻害剤は、前記対象に局所投与され、
前記皮膚の障害、疾患、又は状態は、低メラニン症(hypomelanosis)、特発性滴状低メラニン症、ぶち症、白色粃糠疹、癜風、進行性黄斑低メラニン症、白斑(vitiligo)、ワールデンブルグ症候群、炎症後の色素脱失、創傷後の色素沈着過剰、又はそれらの任意の組み合わせである、組成物。 - 有効量のカゼインキナーゼ1阻害剤を含む、それを必要とする対象の皮膚の障害、疾患、又は状態を予防、改善又は治療するために使用される組成物であって、前記カゼインキナーゼ1阻害剤が、CKI7、D4476、IC261、式Iで表される化合物:
R 1 及びR 2 は、それぞれ独立して、H、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC1-C5アルコキシ、直鎖又は分岐したC1-C5アシル、C5-C15アリール、及びC3-C7ヘテロアリールからなる群から選択され、それぞれは、ハロゲン化物、ヒドロキシ、エステル、エーテル、C5-C15アリール、C3-C7ヘテロアリール、及びアミドの少なくとも1つで任意に置換され;あるいは、R 1 及びR 2 は、それらが結合している窒素原子とともに、N、O、NH、C=N、C=O及びSO 2 の少なくとも1つを任意に含み、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、ハロゲン化物及びシアノの少なくとも1つで任意に置換されてもよい4~7員の飽和、不飽和または芳香環を形成し;
R 3 及びR 4 は、それぞれ独立して、H;それらは、必要に応じてハロゲン化物、ヒドロキシ、アルコキシ、C5-C15アリール、C3-C7ヘテロアリール、エステル及びアミドの少なくとも1つで任意に置換された直鎖又は分岐したC1-C8アルキルからなる群から選択され;又は
R 1 又はR 2 は、R 3 とそれらがそれぞれ結合している炭素原子及び窒素原子とともに、N、NH、O、C=N、C=O、及びSO 2 の少なくとも1つで任意に含み、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、カルボニル、及びハロゲン化物の少なくとも1つで任意に置換されてもよい、4~7員の飽和、不飽和又は芳香環を形成し;
R 5 及びR 8 は、それぞれ独立して、H、ハロゲン化物;少なくとも1個のハロゲン化物で任意に置換される、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、及び直鎖又は分岐したC2-C8アルキニルからなる群から選択され;
R 6 は、直鎖又は分岐したC1-C8アルキル、C3-C7シクロアルキル、4~6員複素環、C5-C15アリール、C3-C7ヘテロアリール、ハロゲン化物、ヒドロキシ、及びC1-C5アルキルハロゲン化物の少なくとも1つで任意に置換される、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、直鎖又は分岐したC2-C8アルキニル、C5-C10シクロアルキル、及び飽和又は不飽和4~6員複素環からなる群から選択され;
R 7 は、C3-C7シクロアルキル、4~6員の複素環、C5-C15アリール、C3-C7ヘテロアリール、ハロゲン化物、ヒドロキシ、及びC1-C5アルキルハロゲン化物の少なくとも1つで任意に置換される直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、及び直鎖又は分岐したC2-C8アルキニルからなる群から選択される)、
式IIで表される化合物、式IIIで表される化合物、式IVで表される化合物、式Vで表される化合物及び式VIで表される化合物:
(III)、
(IV)、
(V)、
(VI)
からなる群から選択され、
前記カゼインキナーゼ1阻害剤は、前記対象に局所投与され、
前記皮膚の障害、疾患、又は状態は、プロオピオメラノコルチン(POMC)、α-メラノサイト刺激ホルモン(α-MSH)、メラノコルチン1受容体(MC1R)、及び小眼球症関連転写因子(MITF)の少なくとも1つが関与するシグナル経路の欠陥により引き起こされる、組成物。 - 有効量のカゼインキナーゼ1阻害剤を含む、それを必要とする対象のユーメラニンレベルを増加させるために使用される組成物であって、前記カゼインキナーゼ1阻害剤が、CKI7、D4476、IC261、式Iで表される化合物:
R1及びR2は、それぞれ独立して、H、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC1-C5アルコキシ、直鎖又は分岐したC1-C5アシル、C5-C15アリール、及びC3-C7ヘテロアリールからなる群から選択され、それぞれは、ハロゲン化物、ヒドロキシ、エステル、エーテル、C5-C15アリール、C3-C7ヘテロアリール、及びアミドの少なくとも1つで任意に置換され;あるいは、R1及びR2は、それらが結合している窒素原子とともに、N、O、NH、C=N、C=O及びSO2の少なくとも1つを任意に含み、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、ハロゲン化物及びシアノの少なくとも1つで任意に置換されてもよい4~7員の飽和、不飽和または芳香環を形成し;
R3及びR4は、それぞれ独立して、H;それらは、必要に応じてハロゲン化物、ヒドロキシ、アルコキシ、C5-C15アリール、C3-C7ヘテロアリール、エステル及びアミドの少なくとも1つで任意に置換された直鎖又は分岐したC1-C8アルキルからなる群から選択され;又は
R1又はR2は、R3とそれらがそれぞれ結合している炭素原子及び窒素原子とともに、N、NH、O、C=N、C=O、及びSO2の少なくとも1つで任意に含み、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、カルボニル、及びハロゲン化物の少なくとも1つで任意に置換されてもよい、4~7員の飽和、不飽和又は芳香環を形成し;
R5及びR8は、それぞれ独立して、H、ハロゲン化物;少なくとも1個のハロゲン化物で任意に置換される、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、及び直鎖又は分岐したC2-C8アルキニルからなる群から選択され;
R6は、直鎖又は分岐したC1-C8アルキル、C3-C7シクロアルキル、4~6員複素環、C5-C15アリール、C3-C7ヘテロアリール、ハロゲン化物、ヒドロキシ、及びC1-C5アルキルハロゲン化物の少なくとも1つで任意に置換される、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、直鎖又は分岐したC2-C8アルキニル、C5-C10シクロアルキル、及び飽和又は不飽和4~6員複素環からなる群から選択され;
R7は、C3-C7シクロアルキル、4~6員の複素環、C5-C15アリール、C3-C7ヘテロアリール、ハロゲン化物、ヒドロキシ、及びC1-C5アルキルハロゲン化物の少なくとも1つで任意に置換される直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、及び直鎖又は分岐したC2-C8アルキニルからなる群から選択される)、
式IIで表される化合物、式IIIで表される化合物、式IVで表される化合物、式Vで表される化合物及び式VIで表される化合物:
(III)
(IV)
(V)
(VI)
からなる群から選択され、
前記カゼインキナーゼ1阻害剤が、前記対象の皮膚においてフェオメラニンレベルよりもユーメラニンレベルを選択的に増加させるために前記対象に局所投与される、組成物。 - 前記ユーメラニンレベルの増加は、前記対象の皮膚の色素沈着を増加させる、請求項6に記載の組成物。
- 前記皮膚の色素沈着は、UVから前記対象を保護する、請求項7に記載の組成物。
- 前記ユーメラニンレベルは、前記対象の表皮で増加する、請求項6に記載の組成物。
- 前記ユーメラニンレベルの増加は、前記対象の表皮におけるKitLレベルの増加を伴う、請求項6に記載の組成物。
- 前記表皮におけるKitLレベルの増加は、前記対象の真皮から前記表皮へのメラノサイトの移動を誘導する、請求項10に記載の組成物。
- 前記対象はヒトである、請求項6に記載の組成物。
- 有効量のカゼインキナーゼ1阻害剤を含む、それを必要とする対象の皮膚細胞におけるカゼインキナーゼ1の活性を阻害するために使用される組成物であって、前記カゼインキナーゼ1阻害剤が、CKI7、D4476、IC261、式Iで表される化合物:
R1及びR2は、それぞれ独立して、H、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC1-C5アルコキシ、直鎖又は分岐したC1-C5アシル、C5-C15アリール、及びC3-C7ヘテロアリールからなる群から選択され、それぞれは、ハロゲン化物、ヒドロキシ、エステル、エーテル、C5-C15アリール、C3-C7ヘテロアリール、及びアミドの少なくとも1つで任意に置換され;あるいは、R1及びR2は、それらが結合している窒素原子とともに、N、O、NH、C=N、C=O及びSO2の少なくとも1つを任意に含み、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、ハロゲン化物及びシアノの少なくとも1つで任意に置換されてもよい4~7員の飽和、不飽和または芳香環を形成し;
R3及びR4は、それぞれ独立して、H;それらは、必要に応じてハロゲン化物、ヒドロキシ、アルコキシ、C5-C15アリール、C3-C7ヘテロアリール、エステル及びアミドの少なくとも1つで任意に置換された直鎖又は分岐したC1-C8アルキルからなる群から選択され;又は
R1又はR2は、R3とそれらがそれぞれ結合している炭素原子及び窒素原子とともに、N、NH、O、C=N、C=O、及びSO2の少なくとも1つで任意に含み、直鎖又は分岐したC1-C5アルキル、C5-C15アリール、C3-C7ヘテロアリール、ヒドロキシ、カルボニル、及びハロゲン化物の少なくとも1つで任意に置換されてもよい、4~7員の飽和、不飽和又は芳香環を形成し;
R5及びR8は、それぞれ独立して、H、ハロゲン化物;少なくとも1個のハロゲン化物で任意に置換される、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、及び直鎖又は分岐したC2-C8アルキニルからなる群から選択され;
R6は、直鎖又は分岐したC1-C8アルキル、C3-C7シクロアルキル、4~6員複素環、C5-C15アリール、C3-C7ヘテロアリール、ハロゲン化物、ヒドロキシ、及びC1-C5アルキルハロゲン化物の少なくとも1つで任意に置換される、直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、直鎖又は分岐したC2-C8アルキニル、C5-C10シクロアルキル、及び飽和又は不飽和4~6員複素環からなる群から選択され;
R7は、C3-C7シクロアルキル、4~6員の複素環、C5-C15アリール、C3-C7ヘテロアリール、ハロゲン化物、ヒドロキシ、及びC1-C5アルキルハロゲン化物の少なくとも1つで任意に置換される直鎖又は分岐したC1-C8アルキル、直鎖又は分岐したC2-C8アルケニル、及び直鎖又は分岐したC2-C8アルキニルからなる群から選択される)、
式IIで表される化合物、式IIIで表される化合物、式IVで表される化合物、式Vで表される化合物及び式VIで表される化合物:
(III)
(IV)
(V)
(VI)
からなる群から選択され、
前記カゼインキナーゼ1阻害剤は、前記対象の皮膚に局所投与される、組成物。 - 前記皮膚細胞と前記有効量の前記カゼインキナーゼ1阻害剤との接触は、前記皮膚細胞のユーメラニンレベルを増加させる、請求項13に記載の組成物。
- 前記皮膚細胞は、表皮細胞である、請求項13に記載の組成物。
- 前記カゼインキナーゼ1阻害剤は、カゼインキナーゼ1α阻害剤である、請求項13に記載の組成物。
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- 2022-07-19 TW TW111127086A patent/TW202320781A/zh unknown
- 2022-07-19 WO PCT/US2022/073864 patent/WO2023004296A1/en active Application Filing
Non-Patent Citations (4)
Title |
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Cell, 2018, Vol.175 No.1, p.171-185 |
EMBO Rep., 2004, Vol.5 No.1, p.60-65 |
J Biol Chem., 2000, Vol.275 No.26, p.20052-60 |
Proc Natl Acad Sci U S A ., 2017, Vol.114 No.38, p.E8035-E8044.,doi: 10.1073/pnas.1702763114. |
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EP4351580A1 (en) | 2024-04-17 |
JP2023014969A (ja) | 2023-01-31 |
TW202320781A (zh) | 2023-06-01 |
CN117813091A (zh) | 2024-04-02 |
WO2023004296A1 (en) | 2023-01-26 |
KR20240036068A (ko) | 2024-03-19 |
US20230053307A1 (en) | 2023-02-16 |
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