JP2020502050A5

JP2020502050A5 -

Info

Publication number: JP2020502050A5
Application number: JP2019524017A
Authority: JP
Filing date: 2017-10-26
Publication date: 2020-07-02
Anticipated expiration: 2037-10-26

Description

ヘテロシクリル部位は、例えば、オキシラニル、アジリニル、１，２−オキサチオラニル、イミダゾリル、チエニル、フリル、テトラヒドロフリル、ピラニル、チオピラニル、チアトレニル、イソベンゾフラニル、ベンゾフラニル、クロメニル、２Ｈ−ピロリル、ピロリル、ピロリニル、ピロリジニル、ピロリジジニル、イミダゾリル、イミダゾリジニル、ベンズイミダゾリル、ピラゾリル、ピラジニル、ピラゾリジニル、チアゾリル、イソチアゾリル、ジチアゾリル、オキサゾリル、イソキサゾリル、ピリジル、ピリミジニル、ピペリジル、ピペラジニル、ピリダジニル、モルホリニル、チオモルホリニル、特にチオモルホリノ、インドリジニル、イソインドリル、３Ｈ−インドリル、インドリル、ベンズイミダゾリル、クマリル、インダゾリル、トリアゾリル、テトラゾリル、プリニル、４／Ｖ−キノリジニル、イソキノリル、キノリル、テトラヒドロキノリル、テトラヒドロイソキノリル、デカヒドロキノリル、オクタヒドロイソキノリル、ベンゾフラニル、ジベンゾフラニル、ベンゾチオフェニル、ジベンゾチオフェニル、フタラジニル、ナフチリジニル、キノキサリル、キナゾリニル、キナゾリニル、シンノリニル、プテリジニル、カルバゾイル、β−カルボリニル、フェナントリジニル、アクリジニル、ペリミジニル、フェナントロリニル、フラザニル、フェナジニル、フェノチアジニル、フェノキサジニル、クロメニル、イソクロマニル、クロマニルなどから選択される。 The heterocyclyl moiety is, for example, oxiranyl, azirinyl, 1,2-oxathiolanyl, imidazolyl, thienyl, furyl, tetrahydrofuryl, pyranyl, thiopyranyl, thiathrenyl, isobenzofuranyl, benzofuranyl, chromenil, 2H-pyrrolyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, Pirorijijiniru, imidazolyl, imidazolidinyl, benzimidazolyl, pyrazolyl, pyrazinyl, pyrazolidinyl, thiazolyl, isothiazolyl, dithiazolyl, oxazolyl, isoxazolyl, pyridyl, pin Rimijiniru, piperidyl, piperazinyl, pyridazinyl, morpholinyl, thiomorpholinyl, especially thiomorpholino, indolizinyl, isoindolyl, 3H- Indolyl, indolyl, benzimidazolyl, coumaryl, indazolyl, triazolyl, tetrazolyl, purinyl, 4/V-quinolidinyl, isoquinolyl, quinolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, decahydroquinolyl, octahydroisoquinolyl, benzofuranyl, dibenzofuran. Nyl, benzothiophenyl, dibenzothiophenyl, phthalazinyl, naphthyridinyl, quinoxalyl, quinazolinyl, quinazolinyl, cinnolinyl, pteridinyl, carbazoyl, β-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, flazanyl, phenazinyl, phenothiazinyl. , Phenoxazinyl, chromenil, isochromanil, chromanyl and the like.

東洋の化粧品は植物ベ−スの構成を好むこともあり、本発明は、デンドロビウム由来のスチルベノイド、特にトランスレスベラトロ−ル、ジヒドロレスベラトロ−ル、又はジヒドロレスベラトロ−ル誘導体を、酸化的ラジカル及びＲＯＳの発生を阻害する可能性を有するメラニン形成の減少において使用することに関する。本組成物は、それを必要とする対象に局所投与により適用される。本組成物は、デイクリ−ム、ナイトクリ−ム、フェイスロ−ション、ボディロ−ション、ボディバタ−、スキンピ−ル、マスク、シャワ−ジェル、サンクリ−ム、サンロ−ション、アフタ−サンクリ−ム、アフタ−サンロ−ション、リップクリ−ム、若しくはリップグロス、又はそれらの類似物の形態である。 Oriental cosmetics may also prefer a plant-based composition, and the present invention provides dendrobium-derived stilbenoids, especially transresveratrol, dihydroresveratrol, or dihydroresveratrol derivatives. It relates to its use in reducing melanogenesis which has the potential to inhibit the generation of oxidative radicals and ROS. The composition is applied by topical administration to a subject in need thereof. The present composition is a day cream, night cream, face lotion, body lotion, body butter, skin peel, mask, shower gel, sun cream, sun lotion, after sun cream, after sun. In the form of sun lotion, lip cream or lip gloss, or the like .

Claims

A compound of formula (4), or a pharmaceutically acceptable salt or prodrug thereof.
here,
R ^2, ^{R 4,} and ^{R 8} are each ^{_{^{^{independently, -OR 11, -OCH 2 R 12}}}} , -OC (O) R 11, -OCH 2 C (O) OR 12 and,, -OC (O) Selected from CH ₂ R ¹² ;
R ¹ , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁹ , and R ¹⁰ are each independently selected from hydrogen, halogen, trifluoromethyl, —OR ¹² , and —OC(O)R ^12. Or R ² and R ³ or R ⁷ and R ^{8 taken} together with the carbon atom to which they are attached form a cyclic group;
R ¹¹ is independently selected from —(CH ₂ )-hydrocarbyl, C _2-10 alkyl, alkenyl, cycloalkyl, aryl and heterocyclyl, each of these groups being optionally 1,2 3, 4, or 5 may be substituted by R ¹³ .
R ¹² is independently selected from hydrocarbyl and heterocyclyl and may be substituted by 1, 2, 3, 4 or 5 R ¹³ .
R ¹³ is independently halogen, trifluoromethyl, cyano, nitro, ^{^{oxo, -OR 14, -C (O)}} R 15, -C (O) N (R 14) R 15, -C (O) ^{^{_{^{OR 14, -OC (O) R}}}} 15, -S (O) 2 R 14, -S (O) 2 N (R 14) R 15, is selected from ^-N ^{(R 14)} R ^15;
R ¹⁴ and R ¹⁵ are each independently hydrogen or selected from hydrocarbyl and heterocyclyl, any of which are optionally hydrogen, cyano, amino, hydroxy, C _1-6 alkyl and C It may be substituted by 1, 2, 3, 4 or 5 substituents independently selected from _1-6 alkoxy.

The compound according to claim 1, wherein the compound is an optically pure stereoisomer, enantiomer, racemate, or diastereomer , or a pharmaceutically acceptable salt or prodrug thereof .

The compound according to claim 1, wherein the compound is selected from DR1, DR2, DR3, DR4, DR5, DR6, DR7, DR8, DR9, DR10, or DR11, each of which is represented by the following formula: A pharmaceutically acceptable salt or prodrug thereof.

A composition for treating, preventing and/or delaying the progression of skin darkening, comprising an effective amount of the compound according to any one of claims 1 to 3 and a pharmaceutically acceptable carrier thereof. A composition comprising.

A compound according to any one of claims 1 to 3 and/or a derivative or chemical thereof in the manufacture of a composition for treating, preventing and/or delaying the progression of skin darkening in a subject in need thereof. Use of Valiant alone and/or in combination with one or more pharmaceutically acceptable skin whitening agents and skin protectants.

Use according to claim 5, wherein the composition is applied topically to the subject.

Use according to claim 5 or 6, wherein the subject is a human.

A compound for skin whitening and skin protection against UV exposure, skin damage and aging represented by the formula (5), or its enantiomer, optically pure stereoisomer, racemate, or diastereomer. Or a pharmaceutically acceptable salt or prodrug thereof.
here,
R ^2, ^{R 4,} and ^{R 8} are each ^{_{^{^{independently, -OR 11, -OCH 2 R 11}}}} , -OC (O) R 11, -OCH 2 C (O) OR 11 and,, -OC (O) Selected from CH ₂ R ¹¹ ;
R ¹ , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁹ , and R ¹⁰ are each independently selected from hydrogen, halogen, trifluoromethyl, —OR ¹¹ , and —OC(O)R ^11. Or R ² and R ³ or R ⁷ and R ^{8 taken} together with the carbon atom to which they are attached form a cyclic group;
R ¹¹ is independently hydrogen or is selected from hydrocarbyl and heterocyclyl, each of these groups optionally being substituted by 1, 2, 3, 4 or 5 R ¹² . Often;
R ¹² is independently halogen, trifluoromethyl, cyano, nitro, ^{^{oxo, -OR 13, -C (O)}} R 14, -C (O) N (R 13) R 14, -C (O) OR ^13, selected from ^{_{^{_{-OC (O) R 14, -S}}}} (O) 2 R 13, -S (O) 2 N (R 13) R 14, -N (R 13) R 14;
R ¹³ and R ¹⁴ are each independently hydrogen or selected from hydrocarbyl and heterocyclyl, any of which is optionally hydrogen, cyano, amino, hydroxy, C _1-6 alkyl and C It may be substituted by 1, 2, 3, 4 or 5 substituents independently selected from _1-6 alkoxy.

A compound for skin whitening and skin protection against UV exposure, skin damage and aging according to claim 8 having the following formula, or an enantiomer thereof, an optically pure stereoisomer, a racemate, Or a diastereomer, or a pharmaceutically acceptable salt or prodrug thereof.

A composition for skin whitening and skin protection against UV exposure, skin damage and aging, which is an effective amount of the compound for skin whitening and skin protection according to claim 8 or 9, and a pharmaceutically acceptable compound thereof. A composition comprising a carrier.

Use of a compound according to claim 8 or 9 in the manufacture of a topical formulation for skin whitening and skin protection against UV exposure, skin damage and aging in a subject in need.

The topical preparations include pastes, solids, powders, particles, emulsions, day creams, night creams, face lotions, body lotions, body butters, skin peels, masks, shower gels, sun creams, Sanro - Deployment aphthous - Sankuri - arm, aphthous - Sanro - Deployment, Rippukuri - arm, or in the form of Rippuguro scan use according to claim 11.

Use according to claim 11 or 12, wherein the subject is a human.

The composition is a paste, a solid, a powder, a particle, an emulsion, a day cream, a night cream, a face lotion, a body lotion, a body butter, a skin peel, a mask, a shower gel, a sun cream, The composition according to claim 4 or 10, which is in the form of a sun lotion, an after-sun cream, or an after-sun lotion.

A method for synthesizing a compound according to claim 3 or 9 from dihydroresveratrol, which comprises the following two synthetic schemes.
Scheme for DR1 to DR3 1:
here,
R ^is, -OR 11, be a -OCH ₂ R ¹¹ or _{^{-OCH 2 C (O) OR 11}} ;
R ¹¹ is hydrocarbyl.
Scheme 2 for DR4 to DR11:
here,
R ^is, -R _11, be -CH ^{2 R 11;}
R ¹¹ is hydrocarbyl optionally substituted by 1, 2, 3, 4 or 5 R ¹² .
R ¹² is halogen or —OR ¹³ ;
R ¹³ is hydrogen or hydrocarbyl.