|
| | CYCLANDELATE Basic information |
| Product Name: | CYCLANDELATE | | Synonyms: | CYCLANDELATE;3,5,5-trimethylcyclohexylamygdalate;3,5,5-trimethylcyclohexylmandelate;alpha-Hydroxybenzeneacetic acid 3,3,5-trimethylcyclohexyl ester;alpha-hydroxybenzeneaceticacid3,3,5-trimethylcyclohexylester;Arto-espasmol;Benzeneacetic acid, alpha-hydroxy-, 3,3,5-trimethylcyclohexyl ester;benzeneaceticacid,alpha-hydroxy-,3,3,5-trimethylcyclohexylester | | CAS: | 456-59-7 | | MF: | C17H24O3 | | MW: | 276.37 | | EINECS: | 207-271-6 | | Product Categories: | Cosmetic Ingredients & Chemicals;CYCLOSPASMOL;456-59-7 | | Mol File: | 456-59-7.mol |  |
| | CYCLANDELATE Chemical Properties |
| Melting point | 55.0-56.5° | | Boiling point | bp14 192-194° | | density | 1.0535 (rough estimate) | | refractive index | 1.5490 (estimate) | | storage temp. | Sealed in dry,Room Temperature | | Water Solubility | Insoluble in water | | solubility | Chloroform (Slightly), Methanol (Slightly, Sonicated) | | form | powder to crystal | | pka | 12.13±0.20(Predicted) | | color | White to Almost white | | Merck | 14,2704 | | EPA Substance Registry System | Benzeneacetic acid, .alpha.-hydroxy-, 3,3,5-trimethylcyclohexyl ester (456-59-7) |
| | CYCLANDELATE Usage And Synthesis |
| Description | Almond (Amygdalus communis L) is a kind of nut from Xinjiang, China.
Traditional Chinese medicine believes that almond can promote blood circulation to
dispel blood stasis, lubricate bowels to relieve constipation, and relieve cough and
asthma. The indications include amenorrhea, fever, wind arthralgia, malaria, blood
stasis and pain, injuries, and blood stasis with constipation. | | Physical properties | Appearance: white or almost white amorphous powder, special smell, and bitter
taste. Solubility: very soluble in ethanol or acetone and almost insoluble in water.
Melting point: 50–62 °C. | | 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. | | Uses | vasodilator | | Definition | ChEBI: The ester obtained by formal condensation of mandelic acid and 3,3,5-tricyclohexanol. It is a direct-acting smooth muscle relaxant used to dilate blood vessels. | | 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. | | Brand name | Cyclospasmol (Wyeth-Ayerst). | | 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 . |
| | CYCLANDELATE Preparation Products And Raw materials |
|
