Licofelone
Grundinformationen
- CAS
156897-06-2- Standard-SMILES
CC1(C)Cc2c(-c3ccccc3)c(-c3ccc(Cl)cc3)c(CC(=O)O)n2C1- InChIKey
UAWXGRJVZSAUSZ-UHFFFAOYSA-N- Summenformel
- C23H22ClNO2
- Durchschnittliche Molmasse
- 379,9 g/mol
- Monoisotopische Masse
- 379,13390662
Überblick
Licofelone is a member of the class of pyrrolizines that is 2,3-dihydro-1H-pyrrolizine substituted by methyl, methyl, carboxymethyl, 4-chlorophenyl, and phenyl groups at positions 2, 2, 5, 6, and 7, respectively. It is a dual inhibitor of cyclooxygenase isoforms and 5-lipoxygenase and is under development for treatment of osteoarthritis. It has a role as a non-steroidal anti-inflammatory drug, an analgesic, an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor, an antineoplastic agent, an anticonvulsant, a neuroprotective agent and an EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor. It is a monocarboxylic acid, a member of pyrrolizines and a member of monochlorobenzenes.
Namen und Bezeichner
- Bevorzugter Name
- Licofelone
- IUPAC
- 2-[2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-5,7-dihydropyrrolizin-3-yl]acetic acid
- Englischer Name
- Licofelone
- Summenformel
- C23H22ClNO2
- Molmasse
- 379.88
Namen und Synonyme
Licofelone156897-06-2ML 3000licofelona6-(4-Chlorophenyl)-2,3-dihydro-2,2-dimethyl-7-phenyl-1H-pyrrolizine-5-acetic acidlicofelonumP5T6BYS22Y2,3-Dihydro-6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-1H-pyrrolizine-5-acetic acid2,2-Dimethyl-6-(4-chlorophenyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)acetic acidDTXSID40166154(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)-acetic acid(2-(4-Chloro-phenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-acetic acid
Weitere Namen anzeigen
icofeLLicofelone, >=99%Licofelone, ML-3000Licofelone USP/EP/BP16-dihydrotanshinone ILicofelone, 10 mM in DMSO1H-Pyrrolizine-5-aceticacid, 6-(4-chlorophenyl)-2,3-dihydro-2,2-diMethyl-7-phenyl-
[2-(4-Chloro-phenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl]-acetic acid(2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)acetic acidRefChem:153386DTXCID3088645ML-3000Licofelone [INN]2-[2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-5,7-dihydropyrrolizin-3-yl]acetic acid[6-(4-CHLOROPHENYL)-2,2-DIMETHYL-7-PHENYL-2,3-DIHYDRO-1H-PYRROLIZIN-5-YL]ACETIC ACID
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 5,2
- Polarare Oberfläche (TPSA)
- 42,2 Ų
- H-Brücken-Donoren
- 1
- H-Brücken-Akzeptoren
- 2
- Frei drehbare Bindungen
- 4
- Schwere Atome
- 27
- Formalladung
- 0
- Komplexität
- 536
Experimentelle und physikochemische Eigenschaften
DrugsPharmaceuticals -> Listed in ZINC15
Physikochemische Eigenschaften
- Schmelzpunkt
- 162 · 162-163°C
- Siedepunkt
- 539.7 · 539.7±50.0 °C(Predicted)
- Dichte
- 1.23 · 1.23
- storage temp.
- -20 °C · -20°C Freezer
- Löslichkeit
- Chloroform, Methanol
- pka
- 4.47 · 4.47±0.10(Predicted)
- Aggregatzustand
- Solid
- Farbe
- Off-White to Light Yellow
- CAS Datenbank
- 156897 · 156897-06-2(CAS DataBase Reference)
Sicherheit und Regulatorisches
Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.
GHS-Klassifizierung
GHS Classification
Warning
H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]
P264, P264+P265, P270, P280, P301+P317, P305+P351+P338, P330, P337+P317, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 38 reports by companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Gefahrenhinweise
Hazard Classes and CategoriesAcute Tox. 4 (100%)
Sicherheitsdaten
- Alarmwort
- Warnung
- Gefahrenhinweise
- Code Gefahrenhinweise Gefahrenklasse Abteilung Alarmwort Symbol P-Code H302
Chemie und Industrie
Pharmakologische Informationen
PharmacodynamicsLicofelone belongs to a novel class of dual-acting anti-inflammatory drugs called COX/LO inhibitors. This group of drugs simultaneously inhibits the enzymes cyclooxygenase (COX) and 5-lipoxygenase (LO).
Mechanism of ActionLicofelone, through combined 5-LOX/COX-inhibition, reduces levels of inflammatory prostaglandins and leukotrienes.
Metabolism/MetabolitesLicofelone has known human metabolites that include (2S,3S,4S,5R)-6-[2-[2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-5,7-dihydropyrrolizin-3-yl]acetyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid, Licofelone M2, and Licofelone M4.
MeSH Pharmacological Classification
Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
Substances that reduce or suppress INFLAMMATION.
Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.
Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.
Anwendungen
BeschreibungCross-talk between lipoxygenase (LO) and cyclooxygenase (COX) pathways has been observed in human osteoarthritic synovial explants which creates an arachidonic acid shunting phenomenon, stimulating interleukin-1β (IL-1β) synthesis. Licofelone is a dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LO) pathways, that decreases levels of prostaglandin E2, leukotriene B4, and lipoxins and prevents lipopolysaccharide-stimulated IL-1β expression. The IC50 values for inhibition of human thrombocyte COX and human 5-LO are 0.16 μM and 0.23 μM, respectively. Unlike other non-steroidal anti-inflammatory drugs, licofelone causes little or no damage to the gastric mucosa in rabbit parietal cells. This is presumably the result of licofelone’s affects on acid-secretory mechanisms, mediated by the inhibition of 5-LO activity.
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