Page last updated: 2024-11-06

nafazatrom

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Nafazatrom is a synthetic, orally active vitamin K antagonist that was developed for the treatment of deep vein thrombosis and pulmonary embolism. However, it was discontinued due to hepatotoxicity and teratogenicity concerns. Nafazatrom acts by inhibiting the synthesis of vitamin K-dependent clotting factors in the liver, similar to other vitamin K antagonists such as warfarin. The compound was synthesized through a multi-step process involving acylation and cyclization reactions. Research into nafazatrom has shed light on the mechanisms of vitamin K antagonist action and the potential for developing safer and more effective anticoagulants. Despite its withdrawal from the market, nafazatrom remains a subject of interest for researchers studying thrombosis and anticoagulation.'

Cross-References

ID SourceID
PubMed CID42923
SCHEMBL ID93681
MeSH IDM0070815

Synonyms (21)

Synonym
nafazatrom ,
bay-g-6575
OPREA1_097893
einecs 261-571-1
bay-g 6575
2,4-dihydro-5-methyl-2-(2-(2-naphthalenyloxy)ethyl)-3h-pyrazol-3-one
3h-pyrazol-3-one, 2,4-dihydro-5-methyl-2-(2-(2-naphthalenyloxy)ethyl)-
nafazatromum [inn-latin]
brn 0665222
bay g 6575
EC-000.2104
5-methyl-2-(2-naphthalen-2-yloxyethyl)-4h-pyrazol-3-one
3-methyl-1-(2-(naphthalen-2-yloxy)ethyl)-1h-pyrazol-5(4h)-one
nafazatromum
nafazatrom [inn:ban]
59040-30-1
unii-k94216221b
SCHEMBL93681
DTXSID00207794
Q27282112
AKOS040753204

Research Excerpts

Overview

Nafazatrom (Bay G 6575) is a novel antithrombotic compound, which acts by stimulation of prostacyclin as well as by inhibition of lipoxygenase enzymes. It has been shown to have beneficial effects in traumatic shock and organ ischemia.

ExcerptReferenceRelevance
"Nafazatrom (Bay g-6575) is a potent antithrombotic agent which has been suggested to stimulate prostacyclin (PGI2) release from the vascular wall. "( Nafazatrom (Bay g-6575), an antithrombotic and antimetastatic agent, inhibits 15-hydroxyprostaglandin dehydrogenase.
Chao, PH; McGiff, JC; Wong, PY, 1982
)
3.15
"Nafazatrom is a pyrazolinone derivative that increases endogenous prostacyclin (PGI2) and has experimental anti-cancer activity."( A clinical study of nafazatrom in advanced human breast cancer.
Coombes, RC; Forgeson, GV; Jones, AL; Powles, TJ, 1991
)
1.33
"Nafazatrom (Bay G 6575) is a novel antithrombotic compound, which acts by stimulation of prostacyclin as well as by inhibition of lipoxygenase enzymes. "( Lack of efficacy of nafazatrom, a novel anti-thrombotic compound, in patients with coronary artery disease.
Mehta, J; Mehta, P; Roy, L, 1985
)
2.04
"Nafazatrom is a safe and well-tolerated agent."( A clinical trial of nafazatrom (Bay g 6575) in advanced cancer.
Blakowski, SA; Cornwell, GG; Coughlin, CT; Fein, S; Nierenberg, DW; O'Donnell, JF; Philipp, E; Zacharski, LR, 1986
)
1.32
"Nafazatrom is an antithrombic drug that has been shown to have beneficial effects in traumatic shock and organ ischemia. "( Effects of nafazatrom on cardiovascular, sympathetic, and endocrine responses to hemorrhagic shock in conscious rats.
Bayorh, MA; Faden, AI; Feuerstein, G; Goldstein, DS; Ramwell, PW; Stull, R; Zerbe, RL, 1985
)
2.1

Effects

Nafazatrom (Bay g 6575) has been shown to be a potent inhibitor of tumor metastasis in preclinical models. It stimulates prostacyclin release from endothelial cells, whereas ASA blocks cyclooxygenase both in platelets and vessel walls.

ExcerptReferenceRelevance
"Nafazatrom has been shown to stimulate prostacyclin release from endothelial cells, whereas ASA blocks cyclooxygenase both in platelets and vessel walls."( Platelet aggregation in arterioles of the hamster cheek pouch and in heart transplants: its tissue-dependent influencibility by acetylsalicylic acid and nafazatrom.
Herrmann, KS; Seuter, F, 1984
)
1.19
"Nafazatrom has no effect on the ability of ram seminal vesicle microsomes to convert PGH2 to PGI2 but protects microsomal PGI2 synthase from inactivation by 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid."( Mechanism of the stimulation of prostaglandin H synthase and prostacyclin synthase by the antithrombotic and antimetastatic agent, nafazatrom.
Das, M; Eling, TE; Honn, KV; Marnett, LJ; Ochs, RC; Pagels, WR; Siedlik, PH; Tainer, BE; Warnock, RH, 1984
)
1.19
"Nafazatrom (Bay g 6575) has been shown to be a potent inhibitor of tumor metastasis in preclinical models. "( A clinical trial of nafazatrom (Bay g 6575) in advanced cancer.
Blakowski, SA; Cornwell, GG; Coughlin, CT; Fein, S; Nierenberg, DW; O'Donnell, JF; Philipp, E; Zacharski, LR, 1986
)
2.04
"Nafazatrom (Bay g 6575) has been reported to raise circulating levels of prostaglandin I2 (PGI2) either by stimulating its synthesis or inhibiting its metabolism, and may also decrease leukotriene synthesis by inhibiting lipoxygenase."( Nafazatrom (Bay g 6575) blunts canine hypoxic pulmonary vasoconstriction: evidence for a prostaglandin-mediated mechanism.
Ensley, RD; Rubin, LJ, 1985
)
2.43

Actions

ExcerptReferenceRelevance
"Nafazatrom blocks the increase in prolactin release caused by the releasing factors TRH and angiotensin II and the increase in prolactin and growth hormone release due to the calcium channel activator maitotoxin."( Nafazatrom, an arachidonate metabolism inhibitor, decreases prolactin and GH release.
Ehreth, JT; Judd, AM; Login, IS; MacLeod, RM, 1986
)
2.44

Treatment

Nafazatrom treatment had no effect on TxB2 production, but significantly altered the production of the platelet 12-HETE (p less than 0.05). Nafaz atrom-treated mice tended to have lighter tumours.

ExcerptReferenceRelevance
"nafazatrom pretreatment) of the LAD-perfused myocardial regions was transmurally ischemic, showing a uniform pattern."( Reduction of acute myocardial ischemia in rabbit hearts by nafazatrom.
Fiedler, VB,
)
1.1
"Nafazatrom-treated animals had a significant reduction in infarct size expressed as a percent of the anatomical area at risk for infarction: 21 +/- 5% in the treated group vs."( Beneficial effects of nafazatrom on ischemic reperfused myocardium.
Abrams, GD; Jolly, SR; Lucchesi, BR; Murtagh, JJ; Pitt, B; Shea, MJ, 1984
)
1.3
"Nafazatrom treatment had no effect on TxB2 production, but significantly altered the production of the platelet 12-HETE (p less than 0.05)."( Effect of nafazatrom on platelet function and release: relationship to symptomatic episodes in patients with peripheral vascular disease.
Buchanan, MR; Butt, RW; Turpie, AG, 1987
)
1.4
"Nafazatrom-treated mice tended to have lighter tumours."( Survival of mice with NC carcinoma is unchanged by drugs that are thought to inhibit thromboxane synthesis or increase prostacyclin formation.
Bennett, A; Carroll, MA; Corrigan, CJ; Melhuish, PB; Patel, S; Stamford, IF, 1986
)
0.99
"Pretreatment with nafazatrom 10 mg/kg p.o."( The effects of nafazatrom on arrhythmias and prostanoid release during coronary artery occlusion and reperfusion in anaesthetized greyhounds.
Coker, SJ; Parratt, JR, 1984
)
0.94
"Pretreatment with nafazatrom reduced the size of the ultimate infarct by 36 and 48 percent (P less than 0.05), and by 28 and 39% (P less than 0.05) with post-ligature nafazatrom treatment."( Reduction of myocardial infarction and dysrhythmic activity by nafazatrom in the conscious rat.
Fiedler, VB, 1983
)
0.83
"Pretreatment with nafazatrom did not affect the decreased pulmonary removal of [3H]-PGE1, exacerbated the haemodynamic response, reduced survival and potentiated the increase in circulating 6-keto-PGF1 alpha."( Effect of nafazatrom and indomethacin on pulmonary removal of prostaglandin E1 after endotoxin in rabbits.
Gillis, CN; Havill, AM; Moalli, R, 1987
)
1

Bioavailability

ExcerptReferenceRelevance
" Oral nafazatrom is ineffective as a 5-lipoxygenase inhibitor in man, probably because of poor bioavailability after administration."( Oral nafazatrom in man: effect on inhaled antigen challenge.
Dollery, CT; Fuller, RW; Maltby, N; Philipp, E; Richmond, R; Ritter, W; Taylor, GW, 1987
)
1.27

Dosage Studied

ExcerptRelevanceReference
" Two dosing schedules were used: (a) on Days 5 through 19 and (b) on Day 5 until death."( Drug treatments for metastasis of the Lewis lung carcinoma: lack of correlation between inhibition of lung metastasis and survival.
Bemis, KG; Campbell, JB; Matsumoto, K; Merriman, RL; Shackelford, KA; Tanzer, LR, 1989
)
0.28
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (8)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Polyunsaturated fatty acid 5-lipoxygenaseRattus norvegicus (Norway rat)IC50 (µMol)17.12500.00462.018210.0000AID179757; AID6855; AID6870; AID7079
Cytochrome P450 11B1, mitochondrialRattus norvegicus (Norway rat)IC50 (µMol)100.00000.49503.52895.0000AID179759
Sodium- and chloride-dependent GABA transporter 1Rattus norvegicus (Norway rat)IC50 (µMol)100.00000.00132.22068.3000AID179759
Sodium- and chloride-dependent GABA transporter 2Rattus norvegicus (Norway rat)IC50 (µMol)100.00000.00321.79008.3000AID179759
Sodium- and chloride-dependent GABA transporter 3Rattus norvegicus (Norway rat)IC50 (µMol)100.00000.00321.54318.3000AID179759
Prostaglandin G/H synthase 2 Rattus norvegicus (Norway rat)IC50 (µMol)75.00000.00291.786810.0000AID161024; AID179759
Sodium- and chloride-dependent betaine transporterRattus norvegicus (Norway rat)IC50 (µMol)100.00000.00321.54318.3000AID179759
Prostaglandin G/H synthase 1 Rattus norvegicus (Norway rat)IC50 (µMol)75.00000.00291.823210.0000AID161024; AID179759
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (15)

Assay IDTitleYearJournalArticle
AID7079Iin vitro inhibition of 5-lipoxygenase activity in rat basophil leukemia type 1(RBL1) cell homogenates, (reduction of [14C]-5-HETE formation)1990Journal of medicinal chemistry, Oct, Volume: 33, Issue:10
Penta- and hexadienoic acid derivatives: a novel series of 5-lipoxygenase inhibitors.
AID161024In vitro for prostaglandin G/H synthase inhibitory activity against rat basophil leukemia type 1 cell homogenates, by measuring the radioactivity of [14C]-PGD21990Journal of medicinal chemistry, Oct, Volume: 33, Issue:10
Penta- and hexadienoic acid derivatives: a novel series of 5-lipoxygenase inhibitors.
AID101295Ex vivo inhibition of LTB4 production was measured in dog blood1991Journal of medicinal chemistry, Mar, Volume: 34, Issue:3
Indazolinones, a new series of redox-active 5-lipoxygenase inhibitors with built-in selectivity and oral activity.
AID6855In vitro inhibition of 5-lipoxygenase in rat (peritoneal assay)1990Journal of medicinal chemistry, Oct, Volume: 33, Issue:10
Penta- and hexadienoic acid derivatives: a novel series of 5-lipoxygenase inhibitors.
AID107938Inhibition of 5-HETE mammalian lipoxygenase at a concentration 20 uM1990Journal of medicinal chemistry, Apr, Volume: 33, Issue:4
Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes.
AID107939Inhibition of LTB4 mammalian lipoxygenase at a concentration 20 uM1990Journal of medicinal chemistry, Apr, Volume: 33, Issue:4
Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes.
AID179757In vitro inhibition of LTB4 production was measured in rat blood1991Journal of medicinal chemistry, Mar, Volume: 34, Issue:3
Indazolinones, a new series of redox-active 5-lipoxygenase inhibitors with built-in selectivity and oral activity.
AID179759In vitro inhibition of PGE-2 production was measured in rat blood1991Journal of medicinal chemistry, Mar, Volume: 34, Issue:3
Indazolinones, a new series of redox-active 5-lipoxygenase inhibitors with built-in selectivity and oral activity.
AID132224In vivo inhibition of AA induced ear oedema in mice following topical administration.1990Journal of medicinal chemistry, Oct, Volume: 33, Issue:10
Penta- and hexadienoic acid derivatives: a novel series of 5-lipoxygenase inhibitors.
AID160716Inhibition of Prostaglandin G/H synthase from bovine seminal vesicle at 20 uM concentration1990Journal of medicinal chemistry, Apr, Volume: 33, Issue:4
Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes.
AID107937Inhibition of 15-HETE mammalian lipoxygenase at a concentration 20 uM1990Journal of medicinal chemistry, Apr, Volume: 33, Issue:4
Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes.
AID107813Inhibition of 12-HETE mammalian lipoxygenase at a concentration 20 uM1990Journal of medicinal chemistry, Apr, Volume: 33, Issue:4
Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes.
AID6870Inhibition of 5-lipoxygenase in rat RBL-1 cells1990Journal of medicinal chemistry, Apr, Volume: 33, Issue:4
Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes.
AID93590In vitro methemoglobin Induction at 10e-4 M in lysed human red blood cells1990Journal of medicinal chemistry, Apr, Volume: 33, Issue:4
Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes.
AID132112In vivo inhibition of ear oedema in mice following p.o. administration.1990Journal of medicinal chemistry, Oct, Volume: 33, Issue:10
Penta- and hexadienoic acid derivatives: a novel series of 5-lipoxygenase inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (86)

TimeframeStudies, This Drug (%)All Drugs %
pre-199077 (89.53)18.7374
1990's9 (10.47)18.2507
2000's0 (0.00)29.6817
2010's0 (0.00)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials5 (5.43%)5.53%
Reviews6 (6.52%)6.00%
Case Studies4 (4.35%)4.05%
Observational0 (0.00%)0.25%
Other77 (83.70%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]