115-53-7 Usage
Description
Isolated by Ohta from Cocculus diversifolius DC., this alkaloid forms colourless
crystals from MeOH. It is stated to possess a powerful reflex action and to be aspasm stimulant, finally causing paralysis and death in toxic doses. It is also said
to suppress the hypotensive action of dihydroxyphenylethanolethylamine.
Physical properties
Appearance: acicular crystals (crystallized from benzene). Solubility: soluble in
ethanol, acetone, chloroform, and dilute alkali; slightly soluble in water, ether, and
benzene. Melting point: 219–221?°C. Specific optical rotation:?– 71° (c?=?2.1, ethanol). Its hydrochloride, crystallization (water or ethanol), decomposed at 278?°C.?Its
hydroiodide, needle crystal (crystallized from water), decomposed at 272?°C.?Its
picrate, which is yellow needle crystal, decomposed at 176?°C.?Sinomenine is sensitive to light and heat to decompose.
History
The chemical structure of sinomenine is composed of four rings, A, B, C, and D, similar to the structure of morphine. Ring A is a benzene ring, and ring B
is a half-chair-shaped, six-member ring. The C ring is a twisted-chair-type, sixmember ring that has an a, β-unsaturated ketone structure attached to the B ring. The
D ring is a nitrogen-containing, sixmember ring under the B ring. Its structure is
shown below; the current structural modification of sinomenine is mainly focused
on the A/C active group.
Based on the transformation of the A ring, it was found that the 1-substituted
formyl derivative of sinomenine showed the strongest inhibitory effect on the
inflammatory response of the mouse ear. The 4-substituted p-chlorobenzoyl-sinomenine has the strongest anti-inflammatory and analgesic activity. The biotransformation and chemical synthesis were also used to prepare the di-sinomenine
derivatives linked by carbon and carbon, which was stronger than that of sinomenine and had a strong inhibitory effect on cell inflammatory factors. Sinomenine
derivatives of the C ring with a pyrazine ring have a strong inhibitory effect on T, B
lymphocyte proliferation reaction, which can be used for the preparation of immunomodulatory drugs. The transformation of C ring carbonyl yielded a series of shift
alkali derivatives, with strong anti-inflammatory and analgesic effects. These
attempts are important for the development of new drugs.
Uses
weak abortifacient, immunosuppressant, analgesic, antiinflammatory; LD50 (po) 580 mg/kg; (ip) 285 mg/kg(mouse)
Indications
It is mainly used for the treatment of rheumatoid arthritis and other types of rheumatism and arrhythmia in clinical.
Biological Activity
Natural anti-inflammatory morphinan analog. Causes degranulation of mast cells in mammalian tissues to release histamine and suppresses production of proinflammatory cytokines. Also displays antinociceptive activity, possibly through activation of the μ -opioid receptor. Stimulates short-term renewal of human embryonic stem cells (ESCs) in vitro .
Pharmacology
Sinomenine has anti-inflammatory, immunosuppressive, analgesic sedation, antiarrhythmic, detoxification, and other pharmacological effects, while the half-life of
sinomenine is short. In addition, sinomenine also causes a strong histamine release,
which leads to rash, gastrointestinal reactions, and other side effects, limiting its
wide range of clinical applications.1. Effects on central nervous system(a) Analgesic effect: The chemical structure of sinomenine and morphine are similar (Fig.?3). They both act on the central nervous system with a significant analgesic effect, but the mechanisms are different. It has been shown that the
analgesic effect of sinomenine has nothing to do with the release of histamine.(b) Sedative effect: Sinomenine has an inhibitory effect on the central nervous system. The sedative effect works by inhibiting the excitement of advanced neurological activity. Sinomenine can also eliminate the “anger” response of mice
caused by electrical stimulation, showing a stabilizing effect. In addition,
although, like morphine, it had mainly a sedative effect on the central nervous
system, sinomenine also has some excitatory effects on some parts of the central nervous system, especially the spinal cord.Other effects on the central nervous system: Sinomenine may, to a slight degree,
induce vomiting. Sinomenine also has local anesthetic effects on frog nerve
endings and rabbit cornea that could be applied for local infiltration
anesthesia.2. Effects on peripheral nervous systemSinomenine can reversibly block the neuromuscular transmission, which showed
a concentration-dependent inhibitory effect. Sinomenine had no significant effect
on nerve stem excitability and conductivity.3. Impact on cardiovascular systemSinomenine has a significant antihypertensive effect. Sinomenine also has a significant antagonistic effect on ischemic arrhythmia.4. Anti-inflammatory and antiallergic effectsThe anti-inflammatory effect of sinomenine is significant.
Clinical Use
The treatment of rheumatism and rheumatoid arthritis is one of the most important
clinical applications of sinomenine. Sinomenine is particularly suitable for the treatment of arrhythmia caused by organic heart disease. Sinomenine is used for the
treatment of glomerular disease, which can reduce urinary protein and relieve
hematuria symptoms, and the side effects were significantly lower than that of
tripterygium glycoside tablets, which are commonly used in clinical practice. In
addition, sinomenine can significantly inhibit renal interstitial fibrosis and the production of tissue growth and growth factor TGF-β1. Sinomenine can significantly
delay the development of chronic renal failure and effectively treat ankylosing
spondylitis.
Purification Methods
Crystallise the salt from water (1g/1.5mL) or EtOH. The free base [115-53-7] M 329.4, has m 161o (from EtOH) (and again at 182o) after crystallisation from *C6H6, and [] D -78.9o (c 1, EtOH). The picrate has m 159-162o(dec) (from H2O). [Beilstein 21 II 470, 21 III/IV 6670.]
References
Ohta., Ber. ges. Physiol., 33, 352 (1925)
Ohta, Kitasato., Arch. expo Med., 6, 259, 283 (1925)
Raymond-Hamet., Compt. rend. Soc. Biol., 125, 509 (1937)
Check Digit Verification of cas no
The CAS Registry Mumber 115-53-7 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,1 and 5 respectively; the second part has 2 digits, 5 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 115-53:
(5*1)+(4*1)+(3*5)+(2*5)+(1*3)=37
37 % 10 = 7
So 115-53-7 is a valid CAS Registry Number.
InChI:InChI=1/C19H23NO4/c1-20-7-6-19-10-14(21)16(24-3)9-12(19)13(20)8-11-4-5-15(23-2)18(22)17(11)19/h4-5,9,12-13,22H,6-8,10H2,1-3H3/t12-,13+,19-/m1/s1
115-53-7Relevant articles and documents
Metabolic mechanism and anti-inflammation effects of sinomenine and its major metabolites N-demethylsinomenine and sinomenine-N-oxide
Kou, Fang,Li, Qiang,Lyu, Chunming,Wang, Yuyan,Wei, Hai,Zhou, Wenbin
, (2020)
Aims: Sinomenine (SIN) is clinically used as an anti-rheumatic drug. However, the metabolic and pharmacological mechanisms of SIN combined with its metabolites are unclear. This study aims to explore the cyclic metabolic mechanism of SIN, the anti-inflammation effects of SIN and its major metabolites (N-demethylsinomenine (DS) and sinomenine-N-oxide (SNO)), and the oxidation property of SNO. Materials and methods: SIN was administrated to rats via gavage. Qishe pills (a SIN-containing drug) were orally administrated to humans. The bio-samples were collected to identify SIN's metabolites. Enzymatic and non-enzymatic incubations were used to reveal SIN's metabolic mechanism. Impacts of SIN, SNO and DS on the inflammation-related cytokine's levels and nuclear translocation of NF-κB were evaluated in LPS-induced Raw264.7 cells. ROS induced by SNO (10 μM) was also assessed. Key findings: CYP3A4 and ROS predominantly mediated the formation of SNO, and CYP3A4 and CYP2C19 primarily mediated the formation of DS. Noteworthily, SNO underwent N-oxide reduction both enzymatically, by xanthine oxidase (XOD), and non-enzymatically, by ferrous ion and heme moiety. The levels of IL-6 and TNF-α and nuclear translocation of NF-κB were ameliorated after pretreatment of SIN in LPS-induced Raw264.7 cells, while limited attenuations were observed after pretreatment of DS (SNO) even at 200 μM. In contrast, SNO induced ROS production. Significance: This study elucidated that SIN underwent both enzymatic and non-enzymatic cyclic metabolism and worked as the predominant anti-inflammation compound, while SNO induced ROS production, suggesting more studies of SIN combined with SNO and DS are necessary in case of DDI and potential toxicities.
Design and synthesis of C-ring quinoxaline-substituted sinomenine 1,2,3-triazole derivatives via click reactions
Chen, Xia,Dong, Ling,Gu, Chengwen,Jin, Jie,Lu, Tong,Pan, Hongmei,Tao, Naili,Wang, Ao,Wu, Xuedan,Zhang, Kehua
, p. 699 - 704 (2020/06/03)
The synthesis of C-ring quinoxaline-substituted sinomenine 1,2,3-triazole derivatives at the 4-OH via click reactions is accomplished, and a total of 16 novel sinomenine double N-heterocyclic derivatives are obtained in 74%–95% yields. The C-ring is first transformed into a 1,2-diketone structure under the action of hydrochloric acid, and then reacted with o-phenylenediamine to obtain a C-ring quinoxaline-substituted structure. The 4-OH of sinomenine reacts with chloropropyne to give an alkynyl sinomenine, and then reacts with sodium azide and various benzyl chlorides to give the target compounds. All the synthesized derivatives are characterized by Fourier-transform infrared spectrometry, high resolution mass spectrometry, 1H NMR, and 13C NMR spectroscopy.
