JP2010254656A - カルボキシアミド誘導体及び/またはその塩を活性成分とするscca−1産生抑制剤 - Google Patents
カルボキシアミド誘導体及び/またはその塩を活性成分とするscca−1産生抑制剤 Download PDFInfo
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Abstract
Description
−SCCA高発現マウスにおいて細胞増殖が活性化されている、
−SCCA高発現マウスにおいて表皮肥厚が見られる、
−SCCA−1高発現細胞株において、細胞増殖とSCCA−1発現量に相関性がある、及び
−SCCAノックダウン細胞株において細胞増殖活性が低下する、という知見を得ている(特願2007−279024及びJournal of Cell Biology, 172(7),983-990 (2006)。
[1] 下記の一般式(I)の化合物、
R1、R4、R5はそれぞれ独立して水素原子、C1〜C4のアルキル基又は1〜5個のヒドロキシ基を持つC1〜C6のヒドロキシアルキル基であり、
R2及びR3はそれぞれ独立して水素原子、C1〜C4のアルキル基又は1〜5個のヒドロキシ基を持つC1〜C6のヒドロキシアルキル基であるか、又はそれぞれ−(CH2)n−であってそれらが結合している原子及びカルボニル基と5〜6員環を形成してよく、ここでnは1または2の整数を表す)、
アラントイン及びそれらの塩からなる群から選ばれる少なくとも1種のカルボキシアミド誘導体を活性成分として含有する、SCCA−1(Squamous Cell Carcinoma Antigen 1)産生抑制剤。
[2] [1]前記カルボキシアミド誘導体が
[3] [1]または[2]に記載のカルボキシアミド誘導体及び/またはその塩を有効成分として含有する、細胞増殖異常に起因する疾患を予防及び/または治療するための医薬組成物。
[4] [1]または[2]に記載のカルボキシアミド誘導体及び/またはその塩を有効成分として含有する、表皮肥厚を予防及び/または治療するための医薬組成物。
[5] [1]または[2]に記載のカルボキシアミド誘導体及び/またはその塩を有効成分として含有する、基底細胞癌(basal cell carcinoma : BCC)、有棘細胞癌(squamous cell carcinoma : SCC)、Bowen病(Bowen’s disease)、毛母腫(石灰化上皮腫、pilomatricoma)、脂漏性角化症(sebarrheic keratosis)、光線角化症(日光角化症、actinic keratosis, solar keratosis)など悪性腫瘍(carcinoma)および前癌状態、扁平苔癬様角化症(lichen planus-like keratosis)、良性苔癬様角化症(benign lichenoid keratosis)、軟線腺腫(acrochordon, cutaneous tag)、膿疱性乾癬(pustular psoriasis)、尋常性乾癬(psoriasis vulgaris)など乾癬(psoriasis)、色素性乾皮症(xeroderma pigmentatosum : XP)、アトピー性皮膚炎(atopic dermatitis)、全身性エリテマトーデス(systemic lupus erythematosus : SLE)、円形状全身性エリテマトーデス(discoid lupus erythematosus : DLE)などエリテマトーデス(erythematosus)、汗孔角化症(porokeratosis)、炎症性線上疣贄表皮母斑(inflammatory linear verrucous epidermal naevus : ILVEN)などの母斑や疣贄、肥厚(hyperplasia)を伴う良性角化症から成る群から選定される疾患を治療するための医薬組成物。
ヒトケラチノサイトを培養し、60〜70%コンフルエント状態で各濃度のカルボキシアミド誘導体を添加した。使用したカルボキシアミド誘導体は以下のとおりである:
・ヒトSCCA1
フォワードプライマー 5’-GTGCTATCTGGAGTCCT-3’(配列番号1)
リバースプライマー 5’-CTGTTGTTGCCAGCAA-3’ (配列番号2)
プローブ 5’-CATCACCTACTTCAACT-3’ (配列番号3)
・ヒトG3PDH
フォワードプライマー 5’-GAAGGTGAAGGTCGGAGTC-3’ (配列番号4)
リバースプライマー 5’-GAAGATGGTGATGGGATTTC-3’ (配列番号5)
プローブ 5’-AGGCTGAGAACGGGAAGCTTGT-3’ (配列番号6)
図1は化合物1−(2−ヒドロキシエチル)−2−イミダゾリジノン、1−(2−ヒドロキシエチル)−2−ピロリドン又はエチレン尿素を添加した場合の結果を示す。ネガティブコントロールでは薬剤を添加しておらず、またポジティブコントロールとしてはSCAA−1及びSCAA−2遺伝子発現抑制効果を有することのわかっている1−ピペリジンプロピオン酸(1−PP)(特願2008−903571)を添加した。図に示すとおり、用量依存的なSCCA−1遺伝子発現量の有意な減少が認められた。図2及び図3はアラントイン及び尿素をそれぞれ添加した場合の結果を示し、同様に用量依存的なSCCA−1遺伝子発現量の有意な減少が認められた。
Claims (5)
- 下記の一般式(I)の化合物、
R1、R4、R5はそれぞれ独立して水素原子、C1〜C4のアルキル基又は1〜5個のヒドロキシ基を持つC1〜C6のヒドロキシアルキル基であり、
R2及びR3はそれぞれ独立して水素原子、C1〜C4のアルキル基又は1〜5個のヒドロキシ基を持つC1〜C6のヒドロキシアルキル基であるか、又はそれぞれ−(CH2)n−であってそれらが結合している原子及びカルボニル基と5〜6員環を形成してよく、ここでnは1または2の整数を表す)、
アラントイン及びそれらの塩からなる群から選ばれる少なくとも1種のカルボキシアミド誘導体を活性成分として含有する、SCCA−1(Squamous Cell Carcinoma Antigen 1)産生抑制剤。 - 請求項1又は2記載のカルボキシアミド誘導体及び/またはその塩を有効成分として含有する、細胞増殖異常に起因する疾患を予防及び/または治療するための医薬組成物。
- 請求項1又は2記載のカルボキシアミド誘導体及び/またはその塩を有効成分として含有する、表皮肥厚を予防及び/または治療するための医薬組成物。
- 請求項1又は2に記載のカルボキシアミド誘導体及び/またはその塩を有効成分として含有する、基底細胞癌(basal cell carcinoma : BCC)、有棘細胞癌(squamous cell carcinoma : SCC)、Bowen病(Bowen’s disease)、毛母腫(石灰化上皮腫、pilomatricoma)、脂漏性角化症(sebarrheic keratosis)、光線角化症(日光角化症、actinic keratosis, solar keratosis)など悪性腫瘍(carcinoma)および前癌状態、扁平苔癬様角化症(lichen planus-like keratosis)、良性苔癬様角化症(benign lichenoid keratosis)、軟線腺腫(acrochordon, cutaneous tag)、膿疱性乾癬(pustular psoriasis)、尋常性乾癬(psoriasis vulgaris)など乾癬(psoriasis)、色素性乾皮症(xeroderma pigmentatosum : XP)、アトピー性皮膚炎(atopic dermatitis)、全身性エリテマトーデス(systemic lupus erythematosus : SLE)、円形状全身性エリテマトーデス(discoid lupus erythematosus : DLE)などエリテマトーデス(erythematosus)、汗孔角化症(porokeratosis)、炎症性線上疣贄表皮母斑(inflammatory linear verrucous epidermal naevus : ILVEN)などの母斑や疣贄、肥厚(hyperplasia)を伴う良性角化症から成る群から選定される疾患を治療するための医薬組成物。
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Application Number | Priority Date | Filing Date | Title |
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JP2009110112A JP5561956B2 (ja) | 2009-04-28 | 2009-04-28 | カルボキシアミド誘導体及び/またはその塩を活性成分とするscca−1産生抑制剤 |
KR1020117025347A KR20120024560A (ko) | 2009-04-28 | 2010-04-28 | 카르복시아미드 유도체 및/또는 그의 염을 활성 성분으로 하는 scca-1 생성 억제제 |
PCT/JP2010/057615 WO2010126102A1 (ja) | 2009-04-28 | 2010-04-28 | カルボキシアミド誘導体及び/またはその塩を活性成分とするscca-1産生抑制剤 |
US13/266,663 US20120283302A1 (en) | 2009-04-28 | 2010-04-28 | Scca-1 production inhibitor having a carboxamide derivative and/or a salt thereof as an active ingredient |
CN2010800187427A CN102413823A (zh) | 2009-04-28 | 2010-04-28 | 以羧酰胺衍生物和/或其盐为活性成分的scca-1产生抑制剂 |
EP10769800A EP2425831A4 (en) | 2009-04-28 | 2010-04-28 | SCCA-1 PRODUCTION INHIBITOR WITH A CARBOXAMIDE DERIVATIVE AND / OR A SALT THEREOF AS AN ACTIVE SUBSTANCE |
EP13159033.3A EP2604261A3 (en) | 2009-04-28 | 2010-04-28 | SCCA-1 production inhibitor having a carboxamide derivative and/or a salt thereof as an active ingredient |
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CN102413823A (zh) | 2012-04-11 |
JP5561956B2 (ja) | 2014-07-30 |
EP2604261A2 (en) | 2013-06-19 |
US20120283302A1 (en) | 2012-11-08 |
EP2425831A4 (en) | 2012-09-19 |
EP2604261A3 (en) | 2013-07-10 |
EP2425831A1 (en) | 2012-03-07 |
WO2010126102A1 (ja) | 2010-11-04 |
KR20120024560A (ko) | 2012-03-14 |
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