CAS 81840-15-5|Vesnarinone

Introduction：Basic information about CAS 81840-15-5|Vesnarinone, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Vesnarinone BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Synonyms

Common Name	Vesnarinone
CAS Number	81840-15-5	Molecular Weight	395.45200
Density	1.246g/cm3	Boiling Point	678.3ºC at 760 mmHg
Molecular Formula	C₂₂H₂₅N₃O₄	Melting Point	238.1-239.5° (Tominaga); mp 238.1-239.8° (Shimizu)
MSDS	/	Flash Point	364ºC

Names

Name	6-[4-(3,4-dimethoxybenzoyl)piperazin-1-yl]-3,4-dihydro-1H-quinolin-2-one
Synonym	More Synonyms

Vesnarinone BiologicalActivity

Description	Vesnarinone is a quinolinone derivative, and its pharmacodynamic effects include inhibition of phosphodiesterase III (PDE3) activity, increases in calcium flux and decreases in potassium flux.IC50 value: 1.1 μM (for HERG current)Target: PDE3in vitro: HERG current is inhibited by Vesnarinone with an IC50 of 1.1 μM, whereas KvLQT1/minK current is not significantly depressed by Vesnarinone even at 30 μM. The IC50 value for Vesnarinone inhibition of HERG channels is 1 μM. The IC50 for Vesnarinone inhibition of PDE is reported to be 300 μM. [1] Vesnarinone is a novel cytokine inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Vesnarinone inhibits BLM-induced pulmonary fibrosis, at least in part, by the inhibition of acute lung injuries in the early phase. [2] Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. Vesnarinone inhibits phosphodiesterase, thereby leading to increased intracellular calcium, and also affects numerous myocardial ion channels, resulting in the prolongation of the opening time of sodium channels and the decrease in the delayed outward and inward rectifying potassium current. Vesnarinone has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits.[3] Vesnarinone plays an important role in the regulation of cytokines and suggest that the reduction of cytokine release may contribute to the beneficial effects of the drug in the treatment of heart failure. Vesnarinone inhibits the production of TFN-a and IFN-y by LPS stimulated whole blood from patients with heart failure and from healthy volunteers. [4]in vivo: Vesnarinone reduces the circulating levels of TNF-α. Cumulative evidence showed that a variety of cytokine are involved in the pathogenesis of pulmonary fibrosis. [2]
Related Catalog	Signaling Pathways >>Metabolic Enzyme/Protease >>Phosphodiesterase (PDE)Research Areas >>Infection
References	[1]. Katayama Y, et al. Inhibitory effects of Vesnarinone on cloned cardiac delayed rectifier K(+) channels expressed in a mammalian cell line. J Pharmacol Exp Ther. 2000 Jul;294(1):339-46. [2]. Inage M, et al. Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin. Int J Biol Sci. 2009;5(4):304-10. [3]. Cavusoglu E, et al. Vesnarinone: a new inotropic agent for treating congestive heart failure. J Card Fail. 1995 Jun;1(3):249-57. [4]. Matsumori A, et al. Vesnarinone, a new inotropic agent, inhibits cytokine production by stimulated human blood from patients with heart failure. Circulation. 1994 Mar;89(3):955-8.

Description

Vesnarinone is a quinolinone derivative, and its pharmacodynamic effects include inhibition of phosphodiesterase III (PDE3) activity, increases in calcium flux and decreases in potassium flux.IC50 value: 1.1 μM (for HERG current)Target: PDE3in vitro: HERG current is inhibited by Vesnarinone with an IC50 of 1.1 μM, whereas KvLQT1/minK current is not significantly depressed by Vesnarinone even at 30 μM. The IC50 value for Vesnarinone inhibition of HERG channels is 1 μM. The IC50 for Vesnarinone inhibition of PDE is reported to be 300 μM. [1] Vesnarinone is a novel cytokine inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Vesnarinone inhibits BLM-induced pulmonary fibrosis, at least in part, by the inhibition of acute lung injuries in the early phase. [2] Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. Vesnarinone inhibits phosphodiesterase, thereby leading to increased intracellular calcium, and also affects numerous myocardial ion channels, resulting in the prolongation of the opening time of sodium channels and the decrease in the delayed outward and inward rectifying potassium current. Vesnarinone has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits.[3] Vesnarinone plays an important role in the regulation of cytokines and suggest that the reduction of cytokine release may contribute to the beneficial effects of the drug in the treatment of heart failure. Vesnarinone inhibits the production of TFN-a and IFN-y by LPS stimulated whole blood from patients with heart failure and from healthy volunteers. [4]in vivo: Vesnarinone reduces the circulating levels of TNF-α. Cumulative evidence showed that a variety of cytokine are involved in the pathogenesis of pulmonary fibrosis. [2]

Related Catalog

Signaling Pathways >>Metabolic Enzyme/Protease >>Phosphodiesterase (PDE)Research Areas >>Infection

References

[1]. Katayama Y, et al. Inhibitory effects of Vesnarinone on cloned cardiac delayed rectifier K(+) channels expressed in a mammalian cell line. J Pharmacol Exp Ther. 2000 Jul;294(1):339-46.

[2]. Inage M, et al. Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin. Int J Biol Sci. 2009;5(4):304-10.

[3]. Cavusoglu E, et al. Vesnarinone: a new inotropic agent for treating congestive heart failure. J Card Fail. 1995 Jun;1(3):249-57.

[4]. Matsumori A, et al. Vesnarinone, a new inotropic agent, inhibits cytokine production by stimulated human blood from patients with heart failure. Circulation. 1994 Mar;89(3):955-8.

Chemical & Physical Properties

Density	1.246g/cm3
Boiling Point	678.3ºC at 760 mmHg
Melting Point	238.1-239.5° (Tominaga); mp 238.1-239.8° (Shimizu)
Molecular Formula	C₂₂H₂₅N₃O₄
Molecular Weight	395.45200
Flash Point	364ºC
Exact Mass	395.18500
PSA	71.11000
LogP	2.69180
Index of Refraction	1.601
InChIKey	ZVNYJIZDIRKMBF-UHFFFAOYSA-N
SMILES	COc1ccc(C(=O)N2CCN(c3ccc4c(c3)CCC(=O)N4)CC2)cc1OC
Storage condition	2-8℃

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TL4490000

CHEMICAL NAME :: Piperazine, 1-(3,4-dimethoxybenzoyl)-4-(1,2,3,4-tetrahydro-2-oxo- 6-quinolinyl)-

CAS REGISTRY NUMBER :: 81840-15-5

LAST UPDATED :: 199612

DATA ITEMS CITED :: 16

MOLECULAR FORMULA :: C22-H25-N3-O4

MOLECULAR WEIGHT :: 395.50

WISWESSER LINE NOTATION :: T66 BNVT&J H- AT6N DNTJ DVR CO1 DO1

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 :: >7594 mg/kg

TOXIC EFFECTS :: Liver - other changes Kidney, Ureter, Bladder - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >1200 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes Liver - other changes Kidney, Ureter, Bladder - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >3 gm/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes Liver - other changes Kidney, Ureter, Bladder - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 79300 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >7594 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Skin and Appendages - hair Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >1200 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes Liver - other changes Kidney, Ureter, Bladder - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >1200 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes Liver - other changes Kidney, Ureter, Bladder - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 56300 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >3 gm/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes Liver - other changes Kidney, Ureter, Bladder - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 63300 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: >3 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,922,1987 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1100 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) Reproductive - Effects on Newborn - behavioral

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,875,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 330 mg/kg

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

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,875,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 11 gm/kg

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

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Specific Developmental Abnormalities - eye/ear

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,875,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 3900 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

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

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,898,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 13 gm/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 18,898,1987

Synonyms

vesnarinone

Piteranometozine

6-[4-(3,4-dimethoxy-benzoyl)-1-piperazinyl]-3,4-dihydrocarbostyril

Arkin-Z

3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinoline

DRG-0210

OPC8212

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