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アダパレン

Adapalene

HCID 60164
ノート反応
基本情報名称と識別子物性安全と法規制化学と産業関連反応化合物ノート
部分構造検索類似構造を探す

基本情報

CAS
106685-40-9
標準SMILES
COc1ccc(-c2ccc3cc(C(=O)O)ccc3c2)cc1C12CC3CC(CC(C3)C1)C2
InChIKey
LZCDAPDGXCYOEH-UHFFFAOYSA-N
分子式
C28H28O3
平均分子量
412.5 g/mol
単同位体質量
412.20384475

名称と識別子

優先名称
Adapalene
IUPAC
6-[3-(1-adamantyl)-4-methoxyphenyl]naphthalene-2-carboxylic acid
現地名
アダパレン
英語名
Adapalene
分子式
C28H28O3
分子量
412.52

名称と別名

ADAPALENE106685-40-9DifferinAdaferinAdapalenoCD-271AdapalenumDifferineCD 2716-(3-(1-Adamantyl)-4-methoxyphenyl)-2-naphthoic acidCD2716-[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid
名称をさらに表示
6-[3-(1-アダマンチル)-4-メトキシフェニル]-2-ナフトエ酸6-[3-(アダマンタン-1-イル)-4-メトキシフェニル]-2-ナフタレンカルボン酸6-[4-メトキシ-3-(アダマンタン-1-イル)フェニル]-2-ナフタレンカルボン酸アダパレンアダパレン (JAN)ディフェリン6-{4-メトキシ-3-[(3r)-アダマンタン-1-イル]フェニル}ナフタレン-2-カルボン酸Adapalen6-(3-(AdaMantan-1-yl)-4-Methoxyphenyl)-2-naphthoic acidADPL6-[3-(1-adamantyl)-4-methoxy-phenyl]naphthalene-2-carboxylic acid6-[3-(1-ADAMANTYL)-4-METHOXYPHENYL]-2-NAPHTHALENE CARBOXYLIC ACIDDifferip75(NTR)Adaparin
DTXSID50464816-(4-Methoxy-3-tricyclo[3.3.1.13,7]dec-1-ylphenyl)-2-naphthalenecarboxylic acid1L4806J2QF6-[3-(adamantan-1-yl)-4-methoxyphenyl]naphthalene-2-carboxylic acidIDP-126 Component AdapaleneDTXCID3026481CHEBI:31174CABTREO COMPONENT ADAPALENE

データベース識別子

CAS
106685-40-9
PubChem CID
60164
DTXSID
DTXSID5046481
ChEMBL
CHEMBL1265、CHEMBL4303650
ChEBI
CHEBI:31174
UNII
1L4806J2QF
EC Number
620-513-9
Nikkaji
J399.566F

物性

構造計算による物性

XLogP
7.7
極性表面積
46.5 Ų
水素結合供与体数
1
水素結合受容体数
3
回転可能結合数
4
重原子数
31
形式電荷
0
複雑度
644

実験および物理化学的性質

LogP · 2 件

6.917

8.6

Solubility4.01e-06 g/L
Boiling Point606.3
Melting Point300
Physical DescriptionSolid

物理化学的性質

融点
319 · 319-3220C
沸点
606.3 · 606.3±55.0 °C(Predicted)
比重(密度)
1.233 · 1.233±0.06 g/cm3(Predicted)
貯蔵温度
2 · 2-8°C
溶解性
10 mg/mL · DMSO:>10mg/mL
外見
白い固体
酸解離定数(Pka)
4.2 · 4.2(at 25℃)
色
ホワイトからオフホワイト
Merck
14 · 14,150
安定性
-20 °C · -20°C の DMSO または DMF 溶液で最大 3 か月間保存できます。
主な用途
医薬品(低分子化合物)
InChIKey
LZCDAPDGXCYOEH-UHFFFAOYSA-N

安全と法規制

安全情報は参考情報です。供給元の安全データシート(SDS)、適用法令、専門家による評価に代わるものではありません。

GHS分類

GHS Classification · 6 件

This chemical does not meet GHS hazard criteria for 9.1% (1 of 11) of reports.

Warning

H302 (18.2%): Harmful if swallowed [Warning Acute toxicity, oral];H315 (72.7%): Causes skin irritation [Warning Skin corrosion/irritation];H317 (54.5%): May cause an allergic skin reaction [Warning Sensitization, Skin];H319 (72.7%): Causes serious eye irritation [Warning Serious eye damage/eye irritation];H335 (18.2%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation];H361 (81.8%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

P203, P261, P264, P264+P265, P270, P271, P272, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 11 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.;Reported as not meeting GHS hazard criteria per 1 of 11 reports by companies.;There are 6 notifications provided by 10 of 11 reports by companies with hazard statement code(s).;Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

危険有害性情報

Hazard Classes and CategoriesAcute Tox. 4 (18.2%);Skin Irrit. 2 (72.7%);Skin Sens. 1 (54.5%);Eye Irrit. 2 (72.7%);STOT SE 3 (18.2%);Repr. 2 (81.8%)

毒性情報

Health EffectsChronic ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A.

化学と産業

薬理情報

ATC Code · 3 件

D10AD03

D - Dermatologicals;D10 - Anti-acne preparations;D10A - Anti-acne preparations for topical use;D10AD - Retinoids for topical use in acne;D10AD03 - Adapalene

QD - Dermatologicals;QD10 - Anti-acne preparations;QD10A - Anti-acne preparations for topical use;QD10AD - Retinoids for topical use in acne;QD10AD03 - Adapalene

Pharmacodynamics · 1 件

Adapalene is anticomedogenic, preventing the formation of new comedones and inflammatory lesions, and also acts to reduce inflammation by modulating the innate immune response. Like other retinoid compounds, adapalene is chemically stable but photosensitive; use with sunscreen is recommended. Minor skin irritations, including erythema, scaling, dryness, and stinging/burning, have been reported.

Mechanism of Action · 1 件

Adapalene is used for the treatment/maintenance of mild-to-severe acne (acne vulgaris). Acne is a multifactorial condition, and evidence exists to support multiple mechanisms of action for adapalene. Adapalene binds to retinoic acid receptor (RAR)-beta and RAR-gamma; this complex subsequently binds to one of three retinoid X receptors (RXRs), which as a complex is capable of binding DNA to modulate transcriptional activity. Although the full extent of transcriptional modulation is not described, retinoid activation is generally known to affect cellular proliferation and differentiation, and adapalene has been shown to inhibit HeLa cell proliferation and human keratinocyte differentiation. These effects primarily account for adapalene's comedolytic and anticomedogenic properties. In addition, adapalene modulates the immune response by down-regulating toll-like receptor 2 (TLR-2) expression and inhibiting the transcription factor activator protein 1 (AP-1). TLR-2 recognizes _Cutibacterium acnes_ (formerly _Propionibacterium acnes_), the bacterium primarily associated with acne. TLR-2 activation causes nuclear translocation of AP-1 and downstream pro-inflammatory gene regulation. Therefore, adapalene has a general anti-inflammatory effect, which reduces inflammation-mediated acne symptoms. When used with benzoyl peroxide, which possesses free radical-mediated bactericidal effects, the combination acts synergistically to reduced comedones and inflammatory lesions.

Biological Half-LifeIn one clinical study, after ten days of treatment with 2g of 0.3% cream or gel, the terminal half-life was between 7 and 51 hours, with a mean of 17.2 ± 10.2.

関連反応

6 件
反応記録を作成
HRID 365633 の反応式
HRID 365633反応物としてuspto-grants-2000_10
HRID 990794 の反応式
HRID 990794反応物としてuspto-grants-2002_10
HRID 1537078 の反応式
HRID 1537078生成物として反応物としてTraining data from https://doi.org/10.1039/C8SC04228D (1/10)
HRID 1991923 の反応式
HRID 1991923生成物としてuspto-grants-2010_01
HRID 1991924 の反応式
HRID 1991924生成物としてuspto-grants-2010_01
HRID 2416985 の反応式
HRID 2416985反応物としてuspto-grants-2004_11

化合物ノート

読み込み中…

このページの内容基本情報名称と識別子物性安全と法規制化学と産業関連反応化合物ノート
SMILES
C1=C2C(C=C(C3=CC=C(OC)C(C45CC6CC(CC(C6)C4)C5)=C3)C=C2)=CC=C1C(O)=O
CAS データベース
106685 · 106685-40-9(CAS DataBase Reference)

化学的性質

化学的特性White Crystalline Solid

Adverse Effects · 1 件

Adverse reactions reported from adapalene include photosensitivity, irritation, redness, dryness, itching, and burning. These are usually mild adverse events.;Adapalene is less irritating compared to other topical retinoids. In a blinded, randomized, controlled, parallel-group study of 591 acne patients, a combined safety analysis conducted in the United States and Europe compared adapalene 0.1% gel and tretinoin 0.025% gel. The number of patients discontinuing the study due to adverse events was about twice as high in those using tretinoin (2.4%) compared to adapalene (1.3%). There were no systemic adverse reactions noted in the study. Most of the adverse reactions observed were related to skin irritation. Multiple other studies have demonstrated similar findings.;Adapalene 0.1% and 0.3% have also been compared to tazarotene in multiple studies showing adapalene to be non-inferior in efficacy and demonstrated superior tolerability. The enhanced tolerability of adapalene has been attributed, in part, to the selective affinity to the nuclear RAR-beta and RAR-gamma receptors, as opposed to RAR-alpha. The decreased risk of skin irritation may contribute to better long-term compliance. Exposure to ultraviolet light should be minimized in patients using adapalene gel. Patients exposed to high levels of sun exposure and sensitive to sunlight should exercise caution. Using sunscreen and protective clothing over adapalene-treated areas is suggested when patients cannot avoid exposure to the sunlight.;Rare, severe allergic reactions characteristically demonstrate pruritus, facial edema, lip swelling, and eyelid swelling. If a patient experiences anaphylactic reactions with symptoms, including facial swelling, hives, chest pain, or shortness of breath, adapalene should be discontinued, and the patient should seek immediate medical evaluation.

Exposure RoutesAbsorption of adapalene through human skin is low. Only trace amounts (<0.25 ng/mL) of parent substance have been found in the plasma of acne patients following chronic topical application of adapalene in controlled clinical trials
Toxicity Summary · 2 件

If the adapalene is applied excessively, marked redness, scaling, or skin discomfort may occur. In addition, according to product labeling, chronic ingestion of the drug may lead to the same adverse drug reactions associated with excessive oral intake of vitamin A.

Mechanistically, adapalene binds to specific retinoic acid nuclear receptors (gamma and beta) and retinoid X receptors but does not bind to the cytosolic receptor protein. Although the exact mode of action of adapalene is unknown, it is suggested that topical adapalene may normalize the differentiation of follicular epithelial cells resulting in decreased microcomedone formation.

Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Effects During Pregnancy and Lactation · 1 件

◉ Summary of Use during Lactation;Topical adapalene has not been studied during breastfeeding. Because it is poorly absorbed after topical application, and blood levels are less than 0.25 mcg/L with long-term use, it is probably a low risk to the nursing infant. Absorption should be minimized by applying it to the smallest possible surface area of the body for the shortest time possible. Do not apply to the nipple area and ensure that the infant’s skin does not come into direct contact with the areas of skin that have been treated.;◉ Effects in Breastfed Infants;Relevant published information was not found as of the revision date.;◉ Effects on Lactation and Breastmilk;Relevant published information was not found as of the revision date.

Toxicity DataThe acute oral toxicity of adapalene in mice and rats is greater than 10 mL/kg

安全データ

wgk
nwg
hs_code
2918992090
Hazard Classifications
Repr. 2
ストレージクラス
11 - Combustible Solids
Metabolism/Metabolites · 2 件

Extensive information regarding adapalene metabolism in humans is unavailable, although it is known to accumulate in the liver and GI-tract. In human, mouse, rat, rabbit, and dog cultured hepatocytes, metabolism appears to affect the methoxybenzene moiety but remains incompletely characterized. The major products of metabolism are glucuronides. Approximately 25% of the drug is metabolized; the rest is excreted as parent drug.

Metabolized mainly by O-demethylation, hydroxylation and conjugation, and excretion is primarily by the biliary route. Route of Elimination: Excretion appears to be primarily by the biliary route.

FDA Pharmacological Classification · 6 件

1L4806J2QF

ADAPALENE

Established Pharmacologic Class [EPC] - Retinoid

Chemical Structure [CS] - Retinoids

Adapalene is a Retinoid.

ADAPALENE

MeSH Pharmacological Classification · 2 件

Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.

Drugs used to treat or prevent skin disorders or for the routine care of skin.

Absorption, Distribution and Excretion · 3 件

Adapalene is applied topically and absorbed through the skin. In one clinical study treating patients once per day with 2g of 0.3% gel applied to 2 mg/cm2 of skin, 15 patients had detectable blood plasma adapalene levels (0.1 ng/ml) resulting in a mean Cmax of 0.553 ± 0.466 ng/ml and a mean AUC of 8.37 ± 8.46 ng\*h/ml on day 10.

Adapalene is primarily excreted by the biliary route at about 30 ng/g of the topically applied amount. Approximately 75% of the drug remains unchanged.

Adapalene is rapidly cleared from blood plasma, typically undetectable after 72 hours following topical application.

Cellular LocationsCytoplasm;Extracellular;Membrane

用途と製造

Uses · 2 件

Use (kg) in USA (2002): 78;Consumption (g per capita) in the USA (2002): 0.000278;Calculated removal (%): 97.7

For the topical treatment of comedo, papular and pustular acne (acne vulgaris) of the face, chest or back.

応用分野 · 4 件

用途アダパレン(英語: Adapalene)とは、尋常性ざ瘡(ニキビ)の外用治療剤に使用される有効成分。レチノイド様の作用を有するナフトエ酸(ナフタレンカルボン酸)誘導体である。毛孔性苔癬などの皮膚疾患に適応外使用される。

説明Adapalene is a synthetic retinoid and an agonist of retinoic acid receptors (RARs; Kds = 1,100, 34, and 130 nM for RARα, RARβ, and RARγ, respectively). It inhibits growth and differentiation of sebocytes in a concentration-dependent manner in primary rat preputial cell culture. Adapalene (10 μM) completely inhibits the activity of soybean 15-lipoxygenase (15-LOX) in an enzyme assay and inhibits the 5- and 15-LOX pathways in human blood polymorphonuclear leukocytes (PMNs). It reduces the protein levels of toll-like receptor 2 (TLR2) and IL-10 in skin explants isolated from patients with acne and healthy controls in a concentration-dependent manner but increases the expression of the antigen-presenting protein CD1d in acne skin explants while decreasing it in control explants. It inhibits inflammation in rodent models of ear edema induced by arachidonic acid and carrageenan-induced paw edema. Adapalene (100 μM) also induces apoptosis and inhibits proliferation of CC-531, HT-29, and LoVo colon cancer cells and reduces tumor growth in a DLD-1 colon cancer nude mouse xenograft model in a dose-dependent manner. Formulations containing adapalene have been used in the treatment of acne vulgaris.

使用Adapalene has been used as a retinoic acid receptor (RAR) agonist to study its effects on inhibiting transcription of hepatitis B virus in covalently closed circular DNA (cccDNA). It has also been used as a component to culture mixed lymphocyte reactions (MLR) to study its effects on isolated macrophages.

一般的な説明Adapalene is a third-generation synthetic retinoid and a highly lipophilic compound derived from naphthoic acid. It is widely used in the treatment of acne.

上流・下流製品情報

上流原料

ヨードメタン4-ブロモフェノール1,2-ジブロモエタン塩化亜鉛1-アダマンタノール水素化ナトリウム3-(1-アダマンチル)-4-メトキシフェニルボロン酸6-[(3-アダマンチル-4-メトキシフェニル)]-2-ナフトエ酸エチルエステル炭素ジオンアダパレンメチルエステル

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補足説明

定義ChEBI: A naphthoic acid that is CD437 in which the phenolic hydroxy group has been converted to its methyl ether.