Noscapine (HCID 275196)

名称と識別子

優先名称: Noscapine
IUPAC: (3S)-6,7-dimethoxy-3-[(5R)-4-methoxy-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-3H-2-benzofuran-1-one
現地名: ノスカピン
英語名: Narcotine
分子式: C22H23NO7
分子量: 413.42

名称と別名

noscapine128-62-1NARCOTINETusscapineMethoxyhydrastineTerbenolCoscopinNarcomprenNarcosineVadebexNoscapalinLongatin

名称をさらに表示

カプバールテルベノールススカピンフスコチンコスコピン[3S,(-)]-6,7-ジメトキシ-3-[(5R)-5,6,7,8-テトラヒドロ-4-メトキシ-6-メチル-1,3-ジオキソロ[4,5-g]イソキノリン-5-イル]イソベンゾフラン-1(3H)-オンメルコチン(S)-6,7-ジメトキシ-3-[(5R)-5,6,7,8-テトラヒドロ-4-メトキシ-6-メチル-1,3-ジオキソロ[4,5-g]イソキノリン-5-イル]-1(3H)-イソベンゾフラノンデツッソウノスカピンニパクソンナルコシンノスカパール(3S)-6,7-ジメトキシ-3-[(5R)-5,6,7,8-テトラヒドロ-4-メトキシ-6-メチル-1,3-ジオキソロ[4,5-g]イソキノリン-5-イル]-1(3H)-イソベンゾフラノンナルコンプレン(S)-6,7-ジメトキシ-3α-[[(5R)-5,6,7,8-テトラヒドロ-4-メトキシ-6-メチル-1,3-ジオキソロ[4,5-g]イソキノリン]-5α-イル]-1(3H)-イソベンゾフラノンツスカピンコジペクトフナコチン(-)-α-ナルコチンOpianVadebeCapvalEcasilTerialOpianinnsc5366

Opianine(-)-NarcotineNarcotinNarcotussinNectadonNicolaneNoscapinLyobex

データベース識別子

CAS: 128-62-1、6035-40-1
PubChem CID: 275196
ChEMBL: CHEMBL364713
ChEBI: CHEBI:73237
UNII: 8V32U4AOQU、A4C6WE7BZN
EC Number: 204-899-2
Nikkaji: J9.283E

物性

構造計算による物性

XLogP: 2.7
極性表面積: 75.7 Å²
水素結合供与体数: 0
水素結合受容体数: 8
回転可能結合数: 4
重原子数: 30
形式電荷: 0
複雑度: 647

実験および物理化学的性質

pHNEUTRAL TO LITMUS

OdorODORLESS

TasteVERY BITTER TASTE

Density1.395

Color/Form · 2 件

ORTHORHOMBIC BISPHENOIDAL PRISMS

FINE, WHITE, OR PRACTICALLY WHITE, CRYSTALLINE POWDER

Solubility · 6 件

PKA 6.24; FREELY SOL IN ETHANOL; INSOL IN DIETHYL ETHER /HYDROCHLORIDE/

FINE, WHITE, OR PRACTICALLY WHITE, CRYSTALLINE POWDER; ODORLESS OR HAS SLIGHT ODOR OF ETHANOL; FREELY SOL IN CHLOROFORM & METHANOL; SOL IN ALCOHOL; SPARINGLY SOL IN ACETONE; PRACTICALLY INSOL IN ETHER; SOLN IN WATER IS DEXTROROTATORY; PH OF SOLN (1 IN 20) BETWEEN 2.5 & 3.5 /HYDROCHLORIDE/

HEMIHYDRATE TO TETRAHYDRATE, CRYSTALS; VERY SOL IN WATER /HYDROCHLORIDE/

CRYSTALS; FREELY SOL IN WATER; SOL IN METHANOL, ETHANOL; SLIGHTLY SOL IN ETHYL ACETATE; PRACTICALLY INSOL IN ETHER /CAMPHORSULFONATE/

PRACTICALLY INSOL IN VEGETABLE OILS; SLIGHTLY SOL IN NH4OH, HOT SOLN OF KOH & NAOH

SLIGHTLY SOL IN ALCOHOL & ETHER

物理化学的性質

融点: 174 · 174-176 °C(lit.)
比旋光度: -200 · -200 º (c=1 in chloroform)
沸点: 532.6 °C · 532.6°C (rough estimate)
比重(密度): 1.395 · 1.395
屈折率: 1.5614 · 1.5614 (estimate)
貯蔵温度: -20 °C · -20°C Freezer, Under Inert Atmosphere
溶解性: 96 · 水にほとんど溶けず、アセトンに溶け、エタノールに溶けにくい（96％）。強酸に溶け、溶液を水で希釈すると塩基が析出することがあります。
酸解離定数(Pka): 7.8 · 7.8(at 25℃)
外見: Solid
色: 斜方プリズムまたはalcの頑丈な針
水溶解度: 302.9 mg/L · 302.9mg/L(25℃)
Merck: 13 · 13,6752
NISTの化学物質情報: Narcotine alkaloid(128-62-1)
EPAの化学物質情報: 1 · 1(3H)-Isobenzofuranone, 6,7-dimethoxy-3-[(5R)-5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin-5-yl]-, (3S)- (128-62-1)

化学的性質

化学的特性Crystalline Solid

安全と法規制

GHS分類

GHS Classification · 6 件

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 140 reports by companies from 4 notifications to the ECHA C&L Inventory.；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

Regulatory Information · 2 件

Chemical: 1(3H)-Isobenzofuranone, 6,7-dimethoxy-3-(5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin-5-yl)-, [S-(R*,S*)]-

Status: Active Update: 29-06-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/19776

Other Safety Information · 1 件

IMAP assessments - 1(3H)-Isobenzofuranone, 6,7-dimethoxy-3-(5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin-5-yl)-, [S-(R*,S*)]-: Environment tier I assessment；IMAP assessments - 1(3H)-Isobenzofuranone, 6,7-dimethoxy-3-(5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin-5-yl)-, [S-(R*,S*)]-: Human health tier I assessment

Hazard Classes and Categories · 2 件

Acute Tox. 4 (100%)

Acute toxicity (Oral) - Category 4

毒性情報

Natural Pollution Sources · 2 件

...NATURALLY OCCURRING OPIUM ALKALOID OF BENZYLISOQUINOLINE GROUP...

...NATURALLY OCCURRING (LEVO-FORM) OF ALKALOID NARCOTINE. ... ISOLATED FROM OPIUM IN WHICH IT IS PRESENT IN AMT RANGING FROM 3-10%.

Human Toxicity ExcerptsADVERSE REACTIONS OCCUR INFREQUENTLY & INCL DROWSINESS, HEADACHE, NAUSEA, NONSEASONAL ALLERGIC (VASOMOTOR) RHINITIS, & CONJUNCTIVITIS.

Non-Human Toxicity ExcerptsIN DOGS, DRUG IS POTENT RELEASER OF HISTAMINE, & LARGE DOSES CAUSE BRONCHOCONSTRICTION & TRANSIENT HYPOTENSION. TOXIC DOSES PRODUCE CONVULSIONS IN ANIMALS.

法規制情報

Regulatory Information · 2 件

Chemical: 1(3H)-Isobenzofuranone, 6,7-dimethoxy-3-(5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin-5-yl)-, [S-(R*,S*)]-

Status: Active Update: 29-06-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/19776

安全データ

wgk: 3
rtecs: RD2625000
ridadr: 1544
毒性: cyt-ham:lng 100 mg/L ATSUDG (4),41,80
hs_code: 29329990
risk_code: 22
hazard_code: Xn
safety_code: 24/25
hazard_class: 6.1(b)
packing_group: III
有毒物質データの: 128-62-1(Hazardous Substances Data)

化学と産業

薬理情報

ATC Code · 2 件

R - Respiratory system；R05 - Cough and cold preparations；R05D - Cough suppressants, excl. combinations with expectorants；R05DA - Opium alkaloids and derivatives；R05DA07 - Noscapine

QR - Respiratory system；QR05 - Cough and cold preparations；QR05D - Cough suppressants, excl. combinations with expectorants；QR05DA - Opium alkaloids and derivatives；QR05DA07 - Noscapine

Mechanism of Action · 2 件

Noscapine's antitussive effects appear to be primarily mediated by its sigma receptor agonist activity. Evidence for this mechanism is suggested by experimental evidence in rats. Pretreatment with rimcazole, a sigma specific antagonist, causes a dose-dependent reduction in antitussive activity of noscapine.

...EXCEPT FOR ITS ANTITUSSIVE EFFECT, IT HAS NO SIGNIFICANT ACTIONS ON CNS IN DOSES WITHIN THERAPEUTIC RANGE.

Metabolism/Metabolites · 1 件

MECONIN WAS THE MAJOR URINARY METABOLITE OF RATS, RABBITS, & HUMANS WHO HAD RECEIVED 120, 150 MG/KG & 10 MG, RESPECTIVELY, ORALLY. IT ACCOUNTED FOR APPROX 3, 8, & 2% OF DOSE RESPECTIVELY, AFTER 24 HR. O-DEMETHYLATED METABOLITES WERE ALSO FOUND.

MeSH Pharmacological ClassificationAgents that suppress cough. They act centrally on the medullary cough center. EXPECTORANTS, also used in the treatment of cough, act locally.

Absorption, Distribution and ExcretionITS ANTITUSSIVE POTENCY & ONSET & DURATION OF ACTION ARE APPROX EQUAL, MG FOR MG, TO THOSE OF CODEINE.

Cellular LocationsCytoplasm；Extracellular

用途と製造

Uses · 2 件

MEDICATION

Use (kg; approx.) in Germany (2009): >1000；Consumption (g per capita; approx.) in Germany (2009): 0.0122；Excretion rate: 1；Calculated removal (%): 46.5

Methods of ManufacturingMAILLARD, US PATENT 3,108,106 (1963 TO JACQUES LOGEAIS).

Formulations/PreparationsTUSSCAPINE (FISONS). ORAL: LIQUID 15 MG/5 ML

Use ClassificationPharmaceuticals

General Manufacturing InformationOPIUM ALKALOID, ISOLATED FROM PLANT PAPAVER SOMNIFERUM L PAPAVERACEAE. FIRST ISOLATION: ROBIQUET, ANN CHIM PHYS (2) 5, 275 (1817). EXTRACTABLE FROM WATER INSOLUBLE RESIDUE REMAINING FROM PROCESSING OF OPIUM FOR MANUFACTURE OF MORPHINE.

応用分野 · 3 件

解説ナルコチン．ノスカピンともいう．アヘン中に3～10％含まれるイソキノリンアルカロイドの一つ．融点176 ℃．密度1.395 g cm－3．[α]D－147°(ベンゼン)．クロロホルムに易溶，ベンゼン，アセトンに可溶，エタノール，水に難溶．塩酸塩(融点220～225 ℃)は水溶性の無色の結晶で，麻酔作用は弱く，鎮咳作用が強い．合成品のdl-ナルコチンはグノスコピン(CAS 6035-40-1)とよばれる．LD50 83 mg/kg(ネズミ，静注)．

用途各種の呼吸器疾患時の鎮咳薬

説明A major constituent of opium (Papaver sornni!erurn), this phthalideisolquinoline base was probably first discovered by Derosne, but initially characterized by Robiquet who gave it the formula C23H3S0 7N, changed to that now accepted by Matthiesen and Foster. It crystallizes in colourless needles from EtOH and has [α]D - 198° (c 1.0, CHC13); - 146° (c 2.0, toluene); - 147° (c 1.59, C6H6) and + 50° (1 % HCl). The alkaloid is a weak, monoacidic, tertiary base, forming unstable salts with acids which are dissociated with H20. The hydrochloride crystallizes with varying amounts of H20, is very soluble in water, readily decomposing into basic salts on standing. The platinichloride is amorphous; the oxalate has m.p. 174°C;[α]20D + 39.5° (H20); the phthalate, m.p. 160°C; [α]22D + 115° (CHC13); sesquisulphate, colourless crystals of the hexahydrate and the picrate, m.p. 1 74-S°C. The (+)-bromocamphorsulphonate has m.p. 110- 120°C; [α]D + 100.7° (CHC13) and the corresponding (-)-bromocamphorsul_x0002_phonate, m.p. l80.SoC; [α]D + 29° (CHC13). The alkaloid yields an N-oxide which is a hygroscopic solid; [α]D + 135° (CHC13) furnishing a crystalline hydrochloride, m.p. 193°C; platinichloride, m.p. 175°C and a picrate, m.p. 130°C.The base is unstable to heat and when heated in a sealed tube yields a mixture of dimethylnornarcotine, methylnornarcotine and nornarcotine. On heating with H20 and 150°C, or on boiling with dilute acids, it is hydrolyzed to opianic acid and hydrocotarnine. Similar degradations are brought about by acid oxidation orreduction, e.g. Zn and dilute HCl gives hydrocotarnine and meconin while dilute HN03 yields cotarnine and opianic acid. Pharmacologically, narcotine resembles thebaine (q.v.) in its action, being a reflex stimulant rather than a narcotic.

上流・下流製品情報

上流原料

(3R)-6,7-ジメトキシ-3-[(5R)-5,6,7,8-テトラヒドロ-4-メトキシ-6-メチル-1,3-ジオキソロ[4,5-g]イソキノリン-5-イル]イソベンゾフラン-1(3H)-オン 7-O-DeMethyl α-Narcotine

下流製品

(3S)-3-[(5R)-9-amino-4-methoxy-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-6,7-dimethoxy-3H-2-benzofuran-1-one 1-ヒドロキシ-8-メトキシ-2-メチル-6,7-メチレンジオキシ-1,2,3,4-テトラヒドロイソキノリン (-)-Α-ナルコチンジオール

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補足説明 · 1 件

定義ChEBI: A benzylisoquinoline alkaloid that is 1,2,3,4-tetrahydroisoquinoline which is substituted by a 4,5-dimethoxy-3-oxo-1,3-dihydro-2-benzofuran-1-yl group at position 1, a methylenedioxy group at positions 6-7 and a methoxy group at position 8. Obtained from p ants of the Papaveraceae family, it lacks significant painkilling properties and is primarily used for its antitussive (cough-suppressing) effects.