FOSTEDIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H20NO3PS
Molecular Weight	361.395
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOP(=O)(CC1=CC=C(C=C1)C2=NC3=CC=CC=C3S2)OCC

InChI

InChIKey=FVYRUSCZCWSFLT-UHFFFAOYSA-N

InChI=1S/C18H20NO3PS/c1-3-21-23(20,22-4-2)13-14-9-11-15(12-10-14)18-19-16-7-5-6-8-17(16)24-18/h5-12H,3-4,13H2,1-2H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3902675 | https://www.ncbi.nlm.nih.gov/pubmed/6540806 | Smith, R.D. et al. (2013) 'The Emergence of Drugs which Block Calcium Entry', p.30 Retrieved from https://books.google.ru/books?id=y7DtCAAAQBAJ

Fostedil (KB-944) is a phosphonic acid derivative with potent vasodilator activity. KB-944 has been demonstrated to produce long lasting coronary vasodilator and hypotensive effects in conscious and anesthetized dogs; increase coronary blood flow in isolated, blood perfused heart preparations of dogs; and reduce systemic pressure in conscious normotensive and hypertensive rats. Slow channel calcium entry blockade is thought to contribute to the vasodilator activity of KB-944. Fostedil is longer acting in hypertensive animals than either nifedipine or diltiazem suggesting a potential clinical advantage for this compound. Unexpectedly, fostedil was shown to produce atrial fibrillation in 3 of 10 hypertensive patients in a placebo controlled study. Fostedil had been in phase II clinical trials for the treatment of angina pectoris. However, this research has been discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated L-type calcium channel 92 Target ID: CHEMBL2095229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/4062434 \| https://www.ncbi.nlm.nih.gov/pubmed/4085780 \| JUCKER (2013) 'Progress in Drug Research', p.219 Retrieved from https://books.google.ru/books?id=wZz5BwAAQBAJ	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Angina pectoris 106 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3902675	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2.33 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6542139	12 mg/kg single, oral dose: 12 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		FOSTEDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
17.33 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6542139	12 mg/kg single, oral dose: 12 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		FOSTEDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
25.88 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6542139	12 mg/kg single, intravenous dose: 12 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		FOSTEDIL plasma	Canis lupus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6542139	12 mg/kg single, oral dose: 12 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		FOSTEDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6.42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6542139	12 mg/kg single, intravenous dose: 12 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		FOSTEDIL plasma	Canis lupus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
4% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6542139	12 mg/kg single, oral dose: 12 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		FOSTEDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
200 mg 1 times / day multiple, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3902675 Page: p.294	unhealthy n = 20 Health Status: unhealthy Condition: coronary heart disease Sex: M+F Food Status: UNKNOWN Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/3902675 Page: p.294	Disc. AE: Angina... AEs leading to discontinuation/dose reduction: Angina (5%) Sources: https://pubmed.ncbi.nlm.nih.gov/3902675 Page: p.294

AEs

AE	Significance	Dose	Population
Angina	5% Disc. AE	200 mg 1 times / day multiple, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3902675 Page: p.294	unhealthy n = 20 Health Status: unhealthy Condition: coronary heart disease Sex: M+F Food Status: UNKNOWN Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/3902675 Page: p.294

Sourcing

Vendor/Aggregator	ID	URL
BOC Sciences	75889-62-2	http://www.bocsci.com/description.asp?cas=75889-62-2
Compound Cloud	53421
MuseChem	I006854	https://www.musechem.com/product/I006854.html
Norris Pharm	NSZB-A095389
Tetrahedron	TS79585	http://www.thsci.com/search.do?q=TS79585
eMolecules	76754413	https://orderbb.emolecules.com/search/#?query=76754413

PubMed

Title	Date	PubMed
Antihypertensive effect of KB-944, a new calcium antagonist, in conscious normotensive and hypertensive rats.	1982	6890824
A comparison of nine calcium ion antagonists and propranolol: exercise tolerance, heart rate and ST-segment changes in patients with chronic stable angina pectoris.	1987	3653222

Patents

Sample Use Guides

In Vivo Use Guide

100 mg once daily

Route of Administration: Oral

In Vitro Use Guide

Fostedil (10(-5)-10(-4) M) decreased the action potential duration measured at 30% repolarization and hyperpolarized the resting membrane potential in ventricular trabeculae of the dog heart. In single ventricular cells of the guinea-pig heart, Fostedil (10(-4) M) abolished the slow inward current and produced an outward shift of the late current measured at the end of 200 msec clamp pulse.

Name

Type

Language

FOSTEDIL

Official Name

English

A-53986

Code

English

PHOSPHONIC ACID, P-((4-(2-BENZOTHIAZOLYL)PHENYL)METHYL)-, DIETHYL ESTER

Systematic Name

English

fostedil [INN]

Common Name

English

KB-944

Code

English

DIETHYL ((4-(2-BENZOTHIAZOLYL)PHENYL)METHYL)PHOSPHONATE

Systematic Name

English

PHOSPHONIC ACID, ((4-(2-BENZOTHIAZOLYL)PHENYL)METHYL)-, DIETHYL ESTER

Common Name

English

FOSTEDIL [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578