141579-67-1

Basic information

• Product Name: A 78773
• Synonyms: A 78773
• CAS NO: 141579-67-1
• Molecular Formula: C₁₅H₁₃FN₂O₄
• Molecular Weight: 304.276
• Mol File: 141579-67-1.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 472.9°Cat760mmHg
• Flash Point: 239.8°C
• Appearance: /
• Density: 1.42g/cm³
• Vapor Pressure: 9.5E-10mmHg at 25°C
• Refractive Index: 1.631
• CAS DataBase Reference: A 78773(CAS DataBase Reference)
• NIST Chemistry Reference: A 78773(141579-67-1)
• EPA Substance Registry System: A 78773(141579-67-1)

Safety Data

• Hazardous Substances Data: 141579-67-1(Hazardous Substances Data)

Usage

InChI:InChI=1/C15H13FN2O4/c1-10(18(20)15(17)19)2-5-12-8-9-14(21-12)22-13-6-3-11(16)4-7-13/h3-4,6-10,20H,1H3,(H2,17,19)

Upstream product

• 141580-64-5 4-<5-(4-fluorophenoxy)-2-furyl>-3-butyn-2-ol 
• 141580-54-3 2-[5-(4-fluorophenoxy)-furan-2-yl]-1,1-dibromoethene 
• 141580-63-4 (5-(4-fluorophenoxy)-2-furyl)acetylene 
• 33342-17-5 5-(4'-fluorophenyl)furan-2-carbaldehyde 
• 698-63-5 5-nitrofurane-2-carboxaldehyde 
• 141598-93-8 N,O-bis(phenoxycarbonyl)-N-<4-<5-(4-fluorophenoxy)-2-furyl>-3-butyn-2-yl>hydroxylamine 

Downstream Products

• 141579-87-5 (R)-(+)-N-<3-<5-(4-fluorophenoxy)methyl>-2-furyl>-1-methyl-2-propynyl-N-hydroxyurea 
• 141579-87-5 S(-)-A-79176 

Relevant articles and documents

Lipoxygenase and cyclooxygenase inhibiting compounds

Compounds having the structure STR1 or a pharmaceutically acceptable salt thereof have activity as inhibitors of cylooxygenase and 5-lipoxygenase, reduce the biosynthesis of leukotrienes B4, C4, D4, and E4 and cylooxygenase products such as prostaglandins and thromboxane and are useful in the treatment of inflammatory and allergic disease states. The compounds have the structure indicated above wherein A is selected from (a) optinally substituted carbocyclic aryl, (b) optinally substituted furyl, (c) optinally substituted benzo[b]furyl, (d) optinally substituted thienyl, (e) optinally substituted pyridyloxy, (f) optinally substituted pyridylalkyl, (g) optinally substituted benzo[b]thienyl, (h) optinally substituted pyridyl, (i) optinally substituted quinolyl, and (j) optinally substituted indolyl; X is selected from (a) optionally substituted alkyl, (b) optinally substituted alkenyl, and (c) optinally substituted alkynyl; R1 and R2 are independently selected from hydrogen, hydroxy, and alkyl; and Z is a residue of a non-steroidal anti-inflammatory drug of the general formula Z--COOH.

(R)-(+)-N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]- N-hydroxyurea (ABT-761), a second-generation 5-lipoxygenase inhibitor

Structure-activity optimization of inhibitory potency and duration of action of N-hydroxyurea containing 5-lipoxygenase inhibitors was conducted. The lipophilic heteroaryl template and the link group connecting the template to the N-hydroxyurea pharmacophore were modified. Inhibition of 5- lipoxygenase was evaluated in vitro in a human whole blood assay. An in vitro assay using liver microsomes from monkey was used to evaluate congeners for comparative rates of glucuronidation. (3-Heteroaryl-1-methyl-2-propynyl)-N- hydroxyureas were found to be more resistant to in vitro glucuronidation. The promising inhibitor N-[3-[5-(4-fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]- N-hydroxyurea (6) was found to have stereoselective glucuronidation in monkey and man. The R enantiomer 7 provided longer duration of inhibition as evaluated by an ex vivo whole blood assay. Further optimization of the lipophilic template led to the discovery of (R)-(+)-N-[3-[5-[(4- fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (11) with more effective and prolonged inhibition of leukotriene biosynthesis than zileuton (1) and 7 in monkey and man. The optimized 5-lipoxygenase inhibitor 11 was selected for development as an investigational drug for leukotriene- mediated disorders.