456-59-7 Usage
Originator
Cyclospasmol,Ives,US,1958
History
The chemical synthesis of cyclandelate was first synthesized by Funcke et al. from
Elan Corporation in Ireland using a-hydroxyphenylacetic acid and cis-3,3,5-cycloalkyl
cyclohexanol. The raw material of mandelic acid was obtained by hydrolysis
after benzaldehyde reacted to sodium cyanide. However, sodium cyanide is hypertoxic, and because of its unique structure of a-hydroxy acid, it is easy to
decompose under the acid condition, which leads to more by-products and low
yield. A series of improved methods have been developed, which can reduce the
environmental pollution under the premise of ensuring the yield of Zn/HCOONH4/
C2H5OH system . The method was used to synthesize cyclandelate since then.
However, this drug has not yet been approved by the Food and Drug Administration
in the United States, Canada, and other countries because it easily causes white
blood cell deficiency. It has been withdrawn from the market after drug approval in
Japan, France, and other countries in the 1970s.
Indications
The indications of cyclandelate are arteriosclerosis obliterans, acrocyanosis, cerebral
arteriosclerosis, cerebral insufficiency, cerebrovascular disease, brain trauma,
and post-traumatic brain syndrome.
Manufacturing Process
50 g of dl-mandelic acid are heated for 6 hours at approximately 100°C with
50 g of 3,3,5-trimethylcyclohexanol (mixture of cis and trans isomers), while
passing dry hydrochloric acid gas as a catalyst through the mixture. The
reaction product is subsequently poured out into water. After neutralization
with potassium bicarbonate the ester is extracted with ether. The ether extract
is dried with sodium sulfate, the ether is distilled off and the residue is
distilled in vacuo. The fraction, which has a boiling point of 192° to 194°C at
14 mm, consists of the 3,3,5-trimethylcyclohexyl ester of mandelic acid, which
is obtained in a yield of about 70%. The liquid solidifies to a colorless solid
substance having a melting point of 50° to 53°C, according to US Patent
2,707,193.
It has been found that crude cyclandelate may be purified by the following
procedure. Crude cyclandelate is dissolved in a solvent chosen for convenience
from the class of saturated hydrocarbons. The crude cyclandelate solution is
stirred for a suitable interval, typically 1 to 5 hours, with an aqueous solution
of sodium borohydride (NaBH4) at temperatures ranging from 25° to 65°C.
The preferred temperature range is 40° to 50°C. The pH of the solution may
be adjusted to any desired level in the range between 2.5 to 11.5. The
preferred pH range is 8.0 to 11.0 because at lower pH levels borohydride is
unstable and decomposes rapidly. The amount of sodium borohydride used
ranges from about 0.5 to 2.0 wt % of the amount of cyclandelate present.
At the end of the stirring period cyclandelate is recovered by well-known
procedures. For instance, the aqueous organic layers may be separated
gravimetrically and the product organic layer washed with an appropriate
solvent and then distilled, according to US Patent 3,663,597.
Therapeutic Function
Spasmolytic
World Health Organization (WHO)
Cyclandelate is a papaverine type spasmolytic and vasodilating
drug intended for symptomatic treatment of various peripheral vascular disorders,
such as intermittent claudication in arteriosclerosis obliterans as well as a
treatment for cognitive dysfunction in patients suffering from senile dementia of
the multi-infarct or Alzheimer's type. Cyclandelate remains registered in several
countries.
Pharmacology
The chemical structure and effect of cyclandelate are similar to papaverine. It can
directly relax vascular smooth muscle and relieve the spasm of ileum and uterus
smooth muscle induced by acetylcholine, histamine, and barium chloride in guinea
pig. This effect is three to five times stronger than papaverine. Cyclandelate can also
expand the cardiovascular, cerebrovascular, and renal blood vessels and limb peripheral
vascular and coronary artery, increase blood flow, and promote blood circulation
. It can also increase the tolerance to hypoxia, but the effect on human cerebral
blood flow has not been confirmed. It was reported that cyclandelate can promote
collateral circulation but has little effect on respiration, blood pressure, cardiac output,
and myocardial oxygen consumption. It is safe for long-term administration .
Clinical Use
Cyclandelate can be used for clinical treatment of cerebral arteriosclerosis, cerebral
vascular accident and its sequelae, post-traumatic brain syndrome, coronary arteriosclerosis,
hypertensive heart disease, Raynaud’s disease, thromboangiitis obliterans,
acrocyanosis, and Meniere’s disease .
Check Digit Verification of cas no
The CAS Registry Mumber 456-59-7 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 4,5 and 6 respectively; the second part has 2 digits, 5 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 456-59:
(5*4)+(4*5)+(3*6)+(2*5)+(1*9)=77
77 % 10 = 7
So 456-59-7 is a valid CAS Registry Number.
InChI:InChI=1/C17H24O3/c1-12-9-14(11-17(2,3)10-12)20-16(19)15(18)13-7-5-4-6-8-13/h4-8,12,14-15,18H,9-11H2,1-3H3
456-59-7Relevant articles and documents
Electrochemical two-electron oxygen reduction reaction (ORR) induced aerobic oxidation of α-diazoesters
Chen, Liang,Gao, Meng,Lu, Cuifen,Ma, Chao,Ruan, Mengyao,Wen, Ziyang,Yang, Fan,Yang, Guichun
, p. 2168 - 2171 (2022/02/17)
Electrochemical oxygen reduction reaction (ORR) is a powerful tool for introducing oxygen functional groups in synthetic chemistry. However, compared with the well-developed one-electron oxygen reduction process, the applications of two-electron oxygen re
Selective Transformation of Vicinal Glycols to α-Hydroxy Acetates in Water via a Dehydrogenation and Oxidization Relay Process by a Self-Supported Single-Site Iridium Catalyst
Shen, Lingyun,Chen, Zhe-Ning,Zheng, Qingshu,Wu, Jiajie,Xu, Xin,Tu, Tao
, p. 12833 - 12839 (2021/10/29)
α-Hydroxy acids have attracted broad attention because of their prevalence in bioactive molecules and biodegradable polymers, but their conventional syntheses are usually restricted to aromatic substrates, especially, in a stepwise manner. Herein, we disclose the transformation of alkyl and aryl vicinal glycols to α-hydroxy acetates in water under the air atmosphere with our solid self-supported NHC-Ir single-site catalyst. Both aliphatic and aromatic glycols are compatible with a much higher catalytic efficiency in the presence of this solid single-site catalyst than other viable molecular catalysts (93% vs a dehydrogenation facilitated by the catalyst, and then it proceeds through an unexpected oxidization relay step by oxygen in the air, leading to the α-hydroxy acetate formation. Our protocol can potentially contribute to the valorization of readily available and inexpensive diols.
Cobalt-Catalyzed Transfer Hydrogenation of α-Ketoesters and N-Cyclicsulfonylimides Using H2O as Hydrogen Source
Gao, Yang,Zhang, Xuexin,Laishram, Ronibala Devi,Chen, Jingchao,Li, Kangkui,Zhang, Keyang,Zeng, Guangzhi,Fan, Baomin
supporting information, p. 3991 - 3997 (2019/08/02)
A Co-catalyzed effective transfer hydrogenation of various α-ketoesters and N-cyclicsulfonylimides by safe and environmentally benign H2O as hydrogen source is described. The reaction used easily available and easy to handle zinc metal as a reductant. Interestingly, the catalytic system does not require ligand for reduction of N-cyclicsulfonylimides. (Figure presented.).
Method for selectively catalytically synthesizing mandelate ester compound from metallocene complex
-
Paragraph 0021; 0022; 0068; 0069, (2017/09/26)
The invention discloses a method for selectively catalytically synthesizing a mandelate ester compound from a metallocene complex. According to the method, a perfluoroalkane (aromatic) metallocene complex is used as a catalyst; mandelic acid, derivatives thereof and alcohol are used as main raw materials, wherein benzyl hydroxyls in mandelic acid and a derivative II thereof do not have esterification reaction with carboxy groups of mandelic acid but carboxy groups of mandelic acid and the derivative II thereof have esterification reaction with carboxy groups of alcohol III; the materials highly selectively react in the presence of an organic solvent or without a solvent, so that the mandelate ester compound in higher yield can be acquired. The method has the advantages of lower cost, high yield, simple and convenient operation and no pollution and has potential industrial application prospect. The method can be a low-cost and green method for preparing the mandelate ester compound.
Pharmaceutical composition and process of treatment
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A process for alleviating proliferative skin diseases such as psoriasis, atopic dermatitis, etc. comprising administering to humans, or domesticated animals, topically and/or systemically a composition comprising a pharmaceutical carrier and at least one active compound selected from the groups, substituted alkyl zanthines, tricyclic antidepressants, organic nitrates, antihypertensives, anti-asthma agents and central nervous system depressants and combinations of certain compounds from specifically named groups of compounds.
