CAS 100981-43-9|Ebrotidine

Introduction：Basic information about CAS 100981-43-9|Ebrotidine, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

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

Common Name	Ebrotidine
CAS Number	100981-43-9	Molecular Weight	477.423
Density	1.7±0.1 g/cm3	Boiling Point	672.3±65.0 °C at 760 mmHg
Molecular Formula	C₁₄H₁₇BrN₆O₂S₃	Melting Point	/
MSDS	/	Flash Point	360.4±34.3 °C

Names

Name	N-(4-bromophenyl)sulfonyl-N'-[2-[[2-(diaminomethylideneamino)-1,3-thiazol-4-yl]methylsulfanyl]ethyl]methanimidamide
Synonym	More Synonyms

Ebrotidine BiologicalActivity

Description	Ebrotidine(FI 3542) is a competitive H2-receptor antagonist (Ki= 127.5 nM) with a potent antisecretory activity and evidenced gastroprotection.IC50 Value: 127.5 nM (Ki)[1]; 0.21mg/kg (ED50, histamine- stimulated acid secretion) [2]Target: H2 receptorin vitro: Ebrotidine displaced 3H-thiotidine specific binding to histamine H2-receptors (Ki: 127.5 nmol/l), showing a higher affinity (p < 0.05) than ranitidine (Ki: 190.0 nmol/l) and cimetidine (Ki: 246.1 nmol/l) [1]. in vivo: Following intravenous administration to rats, ebrotidine inhibited histamine- and pentagastrin-stimulated acid secretion in a dose-dependent manner, ED50 being 0.21 and 0.44 mg/kg, respectively [2]. The mean number of gastric erosions seen at endoscopy after treatment with ebrotidine plus ASA (2.0 +/- 0.3) was significantly lower than that after placebo plus ASA (3.7 +/- 0.2). This reduction in lesion core by ebrotidine was accompanied by a significant increase in gastric blood flow (by 15% in corpus and 26% in antrum), by a rise in transmucosal potential difference (by 12%), and by a decrease of mucosal microbleeding [3]. Results of macroscopic assessment revealed that ebrotidine at doses of 50mg and higher/kg body weight effectively prevented mucosal injury, and that the maximal protective effect was achieved by 1h. Physicochemical analysis established that ebrotidine evoked 30% increase in mucus gel dimension, and showed 20% increase in phospholipids, and the content of sulfo- (18%) and sialomucins (21%) [4].
Related Catalog	Signaling Pathways >>GPCR/G Protein >>Histamine ReceptorSignaling Pathways >>Immunology/Inflammation >>Histamine ReceptorResearch Areas >>Inflammation/Immunology
References	[1]. Agut J, Sánchez JC, Sacristán A, Action of ebrotidine, ranitidine and cimetidine on the specific binding to histamine H1- and H2-receptors. Arzneimittelforschung. 1997 Apr;47(4A):447-9. [2]. Palop D, Agut J, Márquez M, Histamine H2-receptor antagonist action of ebrotidine. Effects on gastric acid secretion, gastrin levels and NSAID-induced gastrotoxicity in the rat. Arzneimittelforschung. 1997 Apr;47(4A):439-46. [3]. Konturek SJ, Kwiecien N, Sito E, Effects of ebrotidine on aspirin-induced gastric mucosal damage and blood flow in humans. Scand J Gastroenterol. 1993 Dec;28(12):1047-50. [4]. Piotrowski J, Yamaki K, Morita M, Ebrotidine--a new H2-receptor antagonist with mucosal strengthening activity. Biochem Int. 1992 Mar;26(4):659-67.

Description

Ebrotidine(FI 3542) is a competitive H2-receptor antagonist (Ki= 127.5 nM) with a potent antisecretory activity and evidenced gastroprotection.IC50 Value: 127.5 nM (Ki)[1]; 0.21mg/kg (ED50, histamine- stimulated acid secretion) [2]Target: H2 receptorin vitro: Ebrotidine displaced 3H-thiotidine specific binding to histamine H2-receptors (Ki: 127.5 nmol/l), showing a higher affinity (p < 0.05) than ranitidine (Ki: 190.0 nmol/l) and cimetidine (Ki: 246.1 nmol/l) [1]. in vivo: Following intravenous administration to rats, ebrotidine inhibited histamine- and pentagastrin-stimulated acid secretion in a dose-dependent manner, ED50 being 0.21 and 0.44 mg/kg, respectively [2]. The mean number of gastric erosions seen at endoscopy after treatment with ebrotidine plus ASA (2.0 +/- 0.3) was significantly lower than that after placebo plus ASA (3.7 +/- 0.2). This reduction in lesion core by ebrotidine was accompanied by a significant increase in gastric blood flow (by 15% in corpus and 26% in antrum), by a rise in transmucosal potential difference (by 12%), and by a decrease of mucosal microbleeding [3]. Results of macroscopic assessment revealed that ebrotidine at doses of 50mg and higher/kg body weight effectively prevented mucosal injury, and that the maximal protective effect was achieved by 1h. Physicochemical analysis established that ebrotidine evoked 30% increase in mucus gel dimension, and showed 20% increase in phospholipids, and the content of sulfo- (18%) and sialomucins (21%) [4].

Related Catalog

Signaling Pathways >>GPCR/G Protein >>Histamine ReceptorSignaling Pathways >>Immunology/Inflammation >>Histamine ReceptorResearch Areas >>Inflammation/Immunology

References

[1]. Agut J, Sánchez JC, Sacristán A, Action of ebrotidine, ranitidine and cimetidine on the specific binding to histamine H1- and H2-receptors. Arzneimittelforschung. 1997 Apr;47(4A):447-9.

[2]. Palop D, Agut J, Márquez M, Histamine H2-receptor antagonist action of ebrotidine. Effects on gastric acid secretion, gastrin levels and NSAID-induced gastrotoxicity in the rat. Arzneimittelforschung. 1997 Apr;47(4A):439-46.

[3]. Konturek SJ, Kwiecien N, Sito E, Effects of ebrotidine on aspirin-induced gastric mucosal damage and blood flow in humans. Scand J Gastroenterol. 1993 Dec;28(12):1047-50.

[4]. Piotrowski J, Yamaki K, Morita M, Ebrotidine--a new H2-receptor antagonist with mucosal strengthening activity. Biochem Int. 1992 Mar;26(4):659-67.

Chemical & Physical Properties

Density	1.7±0.1 g/cm3
Boiling Point	672.3±65.0 °C at 760 mmHg
Molecular Formula	C₁₄H₁₇BrN₆O₂S₃
Molecular Weight	477.423
Flash Point	360.4±34.3 °C
Exact Mass	475.975830
PSA	195.24000
LogP	3.37
Vapour Pressure	0.0±2.1 mmHg at 25°C
Index of Refraction	1.740
InChIKey	ZQHFZHPUZXNPMF-UHFFFAOYSA-N
SMILES	NC(N)=Nc1nc(CSCCN=CNS(=O)(=O)c2ccc(Br)cc2)cs1
Storage condition	2-8℃

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DA9507430

CHEMICAL NAME :: Benzenesulfonamide, N-(((2-(((2-((aminoiminomethyl)amino)-4-thiazolyl)met hyl)thio)ethyl)amino) methylene)-4-bromo-, (E)-

CAS REGISTRY NUMBER :: 100981-43-9

LAST UPDATED :: 199712

DATA ITEMS CITED :: 12

MOLECULAR FORMULA :: C14-H17-Br-N6-O2-S3

MOLECULAR WEIGHT :: 477.46

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 :: >8 gm/kg

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

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,490,1997

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 316 mg/kg

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

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,490,1997

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 100 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - dyspnea Kidney, Ureter, Bladder - hematuria

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,490,1997

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 :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,490,1997

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 366 mg/kg

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

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,490,1997

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 107 mg/kg

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

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,490,1997 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 14 gm/kg/4W-I

TOXIC EFFECTS :: Liver - changes in liver weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - changes in testicular weight

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,492,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 91 gm/kg/26W-C

TOXIC EFFECTS :: Behavioral - food intake (animal) Blood - changes in erythrocyte (RBC) count Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,498,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 21700 mg/kg/7W-I

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,492,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 94250 mg/kg/1Y-I

TOXIC EFFECTS :: Gastrointestinal - ulceration or bleeding from small intestine Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Related to Chronic Data - death

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,498,1997 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 56 gm/kg

SEX/DURATION :: male 8 week(s) pre-mating female 2 week(s) pre-mating - 3 week(s) post-birth

TOXIC EFFECTS :: Reproductive - Fertility - other measures of fertility Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,504,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 5 gm/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 47,504,1997

Safety Information

HS Code	2942000000

Customs

HS Code	2942000000

Synonyms

4-Bromo-N-[(E)-({2-[({2-[(diaminomethylene)amino]-1,3-thiazol-4-yl}methyl)sulfanyl]ethyl}imino)methyl]benzenesulfonamide

Ebrotidina [Spanish]

Ebrotidina

Benzenesulfonamide, 4-bromo-N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl]imino]methyl]-

4-bromo-N-{(E)-[(2-{[(2-carbamimidamido-1,3-thiazol-4-yl)methyl]sulfanyl}ethyl)amino]methylidene}benzenesulfonamide

Ebrotidine

Benzenesulfonamide,N-(((2-(((2-((aminoiminomethyl)amino)-4-thiazolyl)methyl)thio)ethyl)amino)methylene)-4-bromo-,(E)

n-p-bromobenzenesulfonyl-n'-[2-[[[2-[(aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]ethyl]formamidine

Ebrotidinum [Latin]

Ebrotiding

N-[[[2-[[[2-[(Aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromobenzenesulfonamide

FI-3542

p-Bromo-N-[[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl]amino]methylene]benzenesulfonamide

Ulsanic

Ebrotidinum

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