Ebrotidine

Names

[ Name ]:
Ebrotidine

[Synonym ]:
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

Biological Activity

[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 Receptor

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research 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.

[Related Small Molecules]

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

[ 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

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2942000000

Related Compounds

The content on this webpage is sourced from various professional data sources. If you have any questions or concerns regarding the content, please feel free to contact service1@chemsrc.com.