Lidoflazine

Names

[ Name ]:
Lidoflazine

[Synonym ]:
4-[4,4-Bis(4-fluorophenyl)butyl]-N-(2,6-dimethylphenyl)-1-piperazineacetamide
2-[4-[4,4-bis(4-fluorophenyl)butyl]piperazin-1-yl]-N-(2,6-dimethylphenyl)acetamide

Biological Activity

[Description]:

Lidoflazine is a high affinity blocker of the HERG (human ether-a-go-go-related gene) K+ channel. Lidoflazine is an antianginal calcium channel blocker that carries a significant risk of QT interval prolongation and ventricular arrhythmia[1].

[Target]

Ca2+

[In Vitro]

Lidoflazine inhibits potently HERG current (IHERG) recorded from HEK 293 cells stably expressing wild-type HERG (IC50 of ~16 nM).

[References]

[1]. https://www.ncbi.nlm.nih.gov/pubmed/15135665

Chemical & Physical Properties

[ Density]:
1.161g/cm3

[ Boiling Point ]:
632.6ºC at 760mmHg

[ Melting Point ]:
158-162ºC

[ Molecular Formula ]:
C₃₀H₃₅F₂N₃O

[ Molecular Weight ]:
491.61500

[ Flash Point ]:
336.4ºC

[ Exact Mass ]:
491.27500

[ PSA ]:
35.58000

[ LogP ]:
5.69880

[ Appearance of Characters ]:
white

[ Index of Refraction ]:
1.581

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: ≥10mg/mL

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TK7910000

CHEMICAL NAME :: 1-Piperazineaceto-2',6'-xylidide, 4-(4,4-bis(p-fluorophenyl)butyl)-

CAS REGISTRY NUMBER :: 3416-26-0

BEILSTEIN REFERENCE NO. :: 0904339

LAST UPDATED :: 199612

DATA ITEMS CITED :: 5

MOLECULAR FORMULA :: C30-H35-F2-N3-O

MOLECULAR WEIGHT :: 491.68

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 20570 ug/kg/8D-I

TOXIC EFFECTS :: Cardiac - arrhythmias (including changes in conduction)

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 22,923,1972

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >3200 mg/kg

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

REFERENCE :: FRPSAX Farmaco, Edizione Scientifica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 32,461,1977

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >3200 mg/kg

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

REFERENCE :: FRPSAX Farmaco, Edizione Scientifica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 32,461,1977

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 :: ARPMAS Archiv der Pharmazie (Weinheim, Germany) (VCH Pub., Inc., 303 NW 12th Ave., Deerfield Beach, FL 33441) V.51-261, 1835-1923; V.305- 1972- Volume(issue)/page/year: 322,359,1989

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 40 mg/kg

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

REFERENCE :: FRXXBL French Demande Patent Document. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #2279383

Safety Information

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
R22

[ Safety Phrases ]:
36

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
TK7910000

Articles

Protective effects of the lazaroid U74500A and lidoflazine on liver preservation with UW solution.

Transpl. Int. 6(5) , 281-4, (1993)

The effect of adding a 21-aminosteroid, U74500A, and a Ca2+ antagonist, lidoflazine, alone and together to UW solution was assessed in a rat liver preservation model. Following preservation, the liver...

Simpson's paradox and clinical trials: what you find is not necessarily what you prove.

Ann. Emerg. Med. 21(12) , 1480-2, (1992)

Expensive clinical trials have become the gold standard for evaluating the efficacy of promising new therapeutic agents. Full exploration of the collected data is routine to maximize the yield of the ...

1,4-Dihydropyridines bearing a pharmacophoric fragment of lidoflazine.

Bioorg. Med. Chem. 4(10) , 1629-35, (1996)

A series of 1,4-dihydropyridines bearing a pharmacophoric fragment of lidoflazine was synthesized. The compounds were evaluated for inotropic, chronotropic, and calcium antagonist activities. All comp...