Timegadine

Names

[ Name ]:
Timegadine

[Synonym ]:
1-Cyclohexyl-2-(2-methyl-4-quinolyl)-3-(2-thiazolyl)guanidine
Guanidine,1-cyclohexyl-2-(2-methyl-4-quinolyl)-3-(2-thiazolyl)
EINECS 275-184-0
Timegadinum [INN-Latin]
N-cyclohexyl-N'-(2-methyl-quinolin-4-yl)-N''-thiazol-2-yl-guanidine
N-cyclohexyl-N''-4-(2-methylquinolyl)-N'-2-thiazolylguanidine
Timegadine
Timegadina [INN-Spanish]
Guanidine,N-cyclohexyl-N'-(2-methyl-4-quinolinyl)-N''-2-thiazolyl

Biological Activity

[Description]:

Timegadine, a new antiinflammatory agent, is found to be a potent, competitive inhibitor of cyclo-oxygenase (COX) and lipo-oxygenase, with IC50s ranging from 5 nM (washed rabbit platelets) to 20 μM (rat brain) for COX and 100 μM for lipo-oxygenase both in the cytosol fraction of horse platelet homogenates, and in washed rabbit platelets.

[Related Catalog]:

Research Areas >> Inflammation/Immunology

[Target]

COX:5 nM (IC50, in rabbit platelets)

COX:20 μM (IC50, in rat brain)

lipo-oxygenase:100 μM (IC50, in horse and washed rabbit platelets)

[In Vitro]

Timegadine, a new antiinflammatory agent, is found to be a potent, competitive inhibitor of of COX and lipo-oxygenase, with IC50s ranging from 5 nM (washed rabbit platelets) to 20 μM (rat brain) for COX and 100 μM for lipo-oxygenase both in the cytosol fraction of horse platelet homogenates, and in washed rabbit platelets[2].

[In Vivo]

Timegadine, a new antiinflammatory agent, is found to be a potent, competitive inhibitor of prostaglandin synthetase which also inhibits cyclo-oxygenase (COX) and lipoxygenase. Daily oral doses of 10 to 30 mg/kg of Timegadine significantly inhibit both the primary and secondary lesions of adjuvant arthritis when the treatment is initiated on the day of the disease induction and continues for 28 days. Timegadine is able specifically to prevent the development of the swelling of the non-injected paw until 28 days after the adjuvant injection when administered for 5 days prior to and 5 days after the induction of the disease, in analogy with the effect of cyclophosphamide[1].

[Animal admin]

Female inbred Lewis rats (body weight ~150 g) are used in adjuvant arthritis and experimental allergic encephalomyelitis experiments. Paw volume is determined by mercury displacement plethismometer. Timegadine is administered orally in a volume of 1 mL/kg body weight, suspended in 0.5% carboxymethylcellulose[1].

[References]

[1]. George S, et al. The influence of food intake on the bioavailability of timegadine, a novel non-steroidal anti-inflammatory drug. Br J Clin Pharmacol. 1983 Apr;15(4):495-8.

[2]. Ahnfelt-Rønne I, et al. A new antiinflammatory compound, timegadine (N-cyclohexyl-N"-4-[2-methylquinolyl]-N'-2-thiazolylguanidine), which inhibits both prostaglandin and 12-hydroxyeicosatetraenoic acid (12-HETE) formation. Biochem Pharmacol. 1980 Dec;29(24):3265-9.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.31 g/cm3

[ Boiling Point ]:
537.6ºC at 760 mmHg

[ Molecular Formula ]:
C₂₀H₂₃N₅S

[ Molecular Weight ]:
365.49500

[ Flash Point ]:
278.9ºC

[ Exact Mass ]:
365.16700

[ PSA ]:
90.44000

[ LogP ]:
5.48550

[ Index of Refraction ]:
1.701

[ Storage condition ]:
2-8℃

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MF0239800

CHEMICAL NAME :: Guanidine, N-cyclohexyl-N'-(2-methyl-4-quinolinyl)-N''-2-thiazol yl-

CAS REGISTRY NUMBER :: 71079-19-1

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C20-H23-N5-S

MOLECULAR WEIGHT :: 365.54

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >1 gm/kg

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

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 23,13,1980