Sarpogrelate Hydrochloride

Names

[ Name ]:
Sarpogrelate Hydrochloride

[Synonym ]:
Butanedioic acid, mono(2-(dimethylamino)-1-((2-(2-(3-methoxyphenyl)ethyl)phenoxy)methyl)ethyl) ester, hydrochloride
4-[1-(dimethylamino)-3-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]propan-2-yl]oxy-4-oxobutanoic acid,hydrochloride
Butanedioic acid, mono[2-(dimethylamino)-1-[[2-[2-(3-methoxyphenyl)ethyl]phenoxy]methyl]ethyl] ester, hydrochloride (1:1)
4-{[1-(Dimethylamino)-3-{2-[2-(3-methoxyphenyl)ethyl]phenoxy}propan-2-yl]oxy}-4-oxobutanoic acid hydrochloride (1:1)
4-{[1-(Dimethylamino)-3-{2-[2-(3-methoxyphenyl)ethyl]phenoxy}-2-propanyl]oxy}-4-oxobutanoic acid hydrochloride (1:1)
UNII:FQN8N8QP1B
Sarpogrelate HCl
Sarpogrelate (hydrochloride)

Biological Activity

[Description]:

Sarpogrelate(MCI-9042) hydrochloride, a selective 5-HT2 antagonist, has been widely used as an anti-platelet agent for the treatment of PAD.Target: 5-HT2 RecepterSarpogrelate is a drug which acts as an antagonist at the 5HT2A and 5-HT2B receptors. Sarpogrelate was shown to have the same affinity as ritanserin for 5-HT2A receptors, with a Ki value of 8.39 nM [1]. Sarpogrelate lacked prominent 5-HT1-like, 5-HT3, beta, H1, H2 and M3 antagonist activity and weakly blocked alpha 1-adrenoceptors (pKB = 6.30). (S)-M-1 showed weak affinity for 5-HT1-like receptors (pKB = 6.30), alpha 1- (pKB = 6.80) and beta- (pKB = 6.54) adrenoceptors, while (R)-M-1 was a weak antagonist at histamine H1 receptors (pKB = 6.49) [2]. After 12 weeks of sarpogrelate administration, FBF and LBF responses during RH showed significant increases from 13.2 +/- 1.7 to 18.1 +/- 2.2 mL/min per 100 mL tissue (P < 0.01) and from 8.2 +/- 0.9 to 14.2 +/- 2.1 mL/min per 100 mL tissue (P < 0.05), respectively. Sarpogrelate-induced augmentation of FBF and LBF responses to RH was maintained at 24 weeks. Long-term oral administration of sarpogrelate improves vascular function in patients with PAD [3].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

Research Areas >> Cardiovascular Disease

[References]

[1]. Nishio, H., A. Inoue, and Y. Nakata, Binding affinity of sarpogrelate, a new antiplatelet agent, and its metabolite for serotonin receptor subtypes. Arch Int Pharmacodyn Ther, 1996. 331(2): p. 189-202.

[2]. Pertz, H. and S. Elz, In-vitro pharmacology of sarpogrelate and the enantiomers of its major metabolite: 5-HT2A receptor specificity, stereoselectivity and modulation of ritanserin-induced depression of 5-HT contractions in rat tail artery. J Pharm Pharma

[3]. Miyazaki, M., et al., Sarpogrelate hydrochloride, a selective 5-HT2A antagonist, improves vascular function in patients with peripheral arterial disease. J Cardiovasc Pharmacol, 2007. 49(4): p. 221-7.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
585.9ºC at 760 mmHg

[ Melting Point ]:
145-148°C

[ Molecular Formula ]:
C₂₄H₃₂ClNO₆

[ Molecular Weight ]:
465.967

[ Flash Point ]:
308.1ºC

[ Exact Mass ]:
465.191803

[ PSA ]:
85.30000

[ LogP ]:
3.99940

[ Vapour Pressure ]:
1.43E-14mmHg at 25°C

[ Storage condition ]:
Desiccate at RT

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: EJ9965500

CHEMICAL NAME :: Butanedioic acid, esters, mono(2-(dimethylamino)-1-((2-(2-(3-methoxyphenyl)ethy l)phenoxy) methyl)ethyl) ester, hydrochloride, (+-)-

CAS REGISTRY NUMBER :: 135159-51-2

LAST UPDATED :: 199609

DATA ITEMS CITED :: 12

MOLECULAR FORMULA :: C24-H31-N-O6.Cl-H

MOLECULAR WEIGHT :: 466.02

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4400 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S667,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 108 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - convulsions or effect on seizure threshold Gastrointestinal - peritonitis

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S667,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >45 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S667,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2550 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S667,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 65 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - convulsions or effect on seizure threshold Gastrointestinal - peritonitis

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S667,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >45 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S667,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >3 gm/kg

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S667,1991 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 117 gm/kg/52W-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - other changes in urine composition Nutritional and Gross Metabolic - weight loss or decreased weight gain Nutritional and Gross Metabolic - changes in potassium

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S673,1991 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6240 mg/kg

SEX/DURATION :: female 17-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S731,1991

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2080 mg/kg

SEX/DURATION :: female 17-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S731,1991

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 7040 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S707,1991

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 27 gm/kg

SEX/DURATION :: male 9 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Maternal Effects - other effects

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 19(Suppl 3),S707,1991

Safety Information

[ Symbol ]:

GHS07, GHS09

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H400

[ Precautionary Statements ]:
P273

[ Hazard Codes ]:
Xn,N

[ Risk Phrases ]:
22-50/53

[ Safety Phrases ]:
60-61

[ RIDADR ]:
UN 3077 9 / PGIII

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

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Related Compounds

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