CAS 74150-27-9|Pimobendan

Introduction：Basic information about CAS 74150-27-9|Pimobendan, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Pimobendan BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Customs
7. Articles28
8. Synonyms

Common Name	Pimobendan
CAS Number	74150-27-9	Molecular Weight	334.372
Density	1.4±0.1 g/cm3	Boiling Point	/
Molecular Formula	C₁₉H₁₈N₄O₂	Melting Point	249 °C(dec.)
MSDS	ChineseUSA	Flash Point	/
Symbol	GHS06	Signal Word	Danger

Names

Name	pimobendan
Synonym	More Synonyms

Pimobendan BiologicalActivity

Description	Pimobendan is a selective inhibitor of PDE3 with IC50 of 0.32 μM.Target: PDE3Pimobendan exhibits selective inhibition of PDE III isolated from guinea pig cardiac muscle with IC50 of 0.32 uM compared to the inhibition of PDE I and PDE II (IC50s >30 μM). In human atrial cells, 100 μM pimobendan significantly increases the L-type calcium current (ICa(L)) (evoked by depolarization to +10 mV from a holding potential of -40 mV) by 250.4% with the half-maximal stimulation (EC50) of 1.13 μM. In rabbit atrial cells, Pimobendan increases ICa(L) at +10 mV by 67.4.%, which is significantly lower than that obtained in human atrial cells Pimobendan shows a beneficial effect on survival in the murine model of EMC virus-induced myocarditis. Administration of Pimobendan significantly increases the final survival rate from 33.6% (control) to 53.3% (0.1 mg/kg) or 66.7% (1 mg/kg). Pimobendan (1 mg/kg) also significantly reduces myocardial cellular infiltration, the level of intracardiac tumor necrosis factor (TNF)-α and interleukin (IL)-1β compared with the control group, which shows no effect on myocardial necrosis, heart weight and body weight. Pimobendan suppresses expression of the intracardiac iNOS gene , causing reduction of intracardiac NO production.
Related Catalog	Signaling Pathways >>Metabolic Enzyme/Protease >>Phosphodiesterase (PDE)Research Areas >>Cardiovascular Disease
References	[1]. Kajimoto K, et al. Contribution of phosphodiesterase isozymes to the regulation of the L-type calcium current in human cardiac myocytes. Br J Pharmacol. 1997 Aug;121(8):1549-56. [2]. Iwasaki A, et al. Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis. J Am Coll Cardiol. 1999 Apr;33(5):1400-7.

Description

Pimobendan is a selective inhibitor of PDE3 with IC50 of 0.32 μM.Target: PDE3Pimobendan exhibits selective inhibition of PDE III isolated from guinea pig cardiac muscle with IC50 of 0.32 uM compared to the inhibition of PDE I and PDE II (IC50s >30 μM). In human atrial cells, 100 μM pimobendan significantly increases the L-type calcium current (ICa(L)) (evoked by depolarization to +10 mV from a holding potential of -40 mV) by 250.4% with the half-maximal stimulation (EC50) of 1.13 μM. In rabbit atrial cells, Pimobendan increases ICa(L) at +10 mV by 67.4.%, which is significantly lower than that obtained in human atrial cells Pimobendan shows a beneficial effect on survival in the murine model of EMC virus-induced myocarditis. Administration of Pimobendan significantly increases the final survival rate from 33.6% (control) to 53.3% (0.1 mg/kg) or 66.7% (1 mg/kg). Pimobendan (1 mg/kg) also significantly reduces myocardial cellular infiltration, the level of intracardiac tumor necrosis factor (TNF)-α and interleukin (IL)-1β compared with the control group, which shows no effect on myocardial necrosis, heart weight and body weight. Pimobendan suppresses expression of the intracardiac iNOS gene , causing reduction of intracardiac NO production.

Related Catalog

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

References

[1]. Kajimoto K, et al. Contribution of phosphodiesterase isozymes to the regulation of the L-type calcium current in human cardiac myocytes. Br J Pharmacol. 1997 Aug;121(8):1549-56.

[2]. Iwasaki A, et al. Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis. J Am Coll Cardiol. 1999 Apr;33(5):1400-7.

Chemical & Physical Properties

Density	1.4±0.1 g/cm3
Melting Point	249 °C(dec.)
Molecular Formula	C₁₉H₁₈N₄O₂
Molecular Weight	334.372
Exact Mass	334.142975
PSA	79.37000
LogP	1.81
Index of Refraction	1.693
InChIKey	GLBJJMFZWDBELO-UHFFFAOYSA-N
SMILES	COc1ccc(-c2nc3ccc(C4=NNC(=O)CC4C)cc3[nH]2)cc1

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UR6373000

CHEMICAL NAME :: 3(2H)-Pyridazinone, 4,5-dihydro-6-(2-(4-methoxyphenyl)-1H-benzimidazol-5- yl)-5-methyl-

CAS REGISTRY NUMBER :: 74150-27-9

LAST UPDATED :: 199612

DATA ITEMS CITED :: 15

MOLECULAR FORMULA :: C19-H18-N4-O2

MOLECULAR WEIGHT :: 334.41

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 :: 950 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes Endocrine - other changes

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >300 mg/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: 25,815,1994

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 72 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - acute pulmonary edema Gastrointestinal - other changes

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >2 gm/kg

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

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: >2 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: 25,815,1994 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 16800 mg/kg/4W-I

TOXIC EFFECTS :: Endocrine - changes in adrenal weight Blood - normocytic anemia Related to Chronic Data - death

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1911 mg/kg/39W-I

TOXIC EFFECTS :: Gastrointestinal - other changes

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 18200 mg/kg/52W-I

TOXIC EFFECTS :: Gastrointestinal - other changes Blood - changes in other cell count (unspecified)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 56 mg/kg/4W-I

TOXIC EFFECTS :: Gastrointestinal - other changes

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1400 mg/kg/4W-I

TOXIC EFFECTS :: Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 56 mg/kg/4W-I

TOXIC EFFECTS :: Cardiac - pericarditis

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 27300 mg/kg/26W-C

TOXIC EFFECTS :: Cardiac - change in rate Cardiac - other changes

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,529,1991 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 24 gm/kg

SEX/DURATION :: male 8 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,415,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 390 mg/kg

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

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,415,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1300 mg/kg

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

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,415,1992

Safety Information

Symbol	GHS06
Signal Word	Danger
Hazard Statements	H301
Precautionary Statements	Missing Phrase - N15.00950417
Hazard Codes	Xi
Risk Phrases	R36/37/38:Irritating to eyes, respiratory system and skin .
Safety Phrases	S26-S37/39
RIDADR	UN 2811 6.1 / PGIII
WGK Germany	3
RTECS	CY8980000
HS Code	29310095

Customs

HS Code	29310095

Articles28

Synthesis, vasorelaxant activity and antihypertensive effect of benzo[d]imidazole derivatives.

Bioorg. Med. Chem. 18 , 3985-91, (2010)

A series of 1H-benzo[d]imidazole analogues of Pimobendan, substituted at position 5 with either -CF(3) or -NO(2), were synthesized using a short synthetic route. All the nitro derivatives were potent,...

Valvular dysplasia and congestive heart failure in a juvenile African penguin (Spheniscus demersus).

J. Zoo Wildl. Med. 45(4) , 987-90, (2014)

Abstract: An aquarium-housed, 6-mo-old African penguin (Spheniscus demersus) presented with acute respiratory distress. Auscultation revealed a grade II-III systolic murmur in the absence of adventiti...

Effects of Single Drug and Combined Short-term Administration of Sildenafil, Pimobendan, and Nicorandil on Right Ventricular Function in Rats With Monocrotaline-induced Pulmonary Hypertension.

J. Cardiovasc. Pharmacol. 65(6) , 640-8, (2015)

This study was designed to assess the progression of pulmonary arterial hypertension (PAH) and the effectiveness of therapy using recently investigated echocardiographic parameters. PAH is characteriz...

Synonyms

(RS)-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one

4,5-Dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-3(2H)-pyridazinone

3(2H)-Pyridazinone, 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-

(±)-UD CG 115BS

6-[2-(4-Methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one

dl-Pimobendan

rac PiMobendan

Vetmedin

UD CG 115 BS

6-[2-(4-Methoxyphenyl)-1H-benzimidazol-6-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one

Pimobendam

Pimobendan

Pimobendanum

UD-CG 115

UNII:34AP3BBP9T

2-(4-methoxyphenyl)-5(6)-(5-methyl-3-oxo-4,5-dihydro-2H-6-pyridazinyl)benzimidazole

3(2H)-Pyridazinone, 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-5-methyl-

MFCD00761648

UNII:9HTU209Z0N

2-(4-methoxy-phenyl)-5-(5-methyl-3-oxo-4,5-dihydro-2H-6-pyridazinyl) benzimidazole

UNII:613JXV89SU

Pimobendane

Acardi

6-[2-(4-Methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone

UD-CG115 BS

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