147511-69-1

Basic information

• Product Name: Pitavastatin
• Synonyms: ITAVASTATIN;PITAVASTATIN;monocalciumbis{(3r,5s,6e)-7-[2-cyclopyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate};PitavastatinCa;PITVASTATIN;(3R,5S,6E)-7-(2-Cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-3,5-dihydroxyhept-6-enoic acid;( )-(3R,5S,6E)-7-(2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl)-3,5-dihydroxy-6-heptenoic acid;6-Heptenoic acid, 7-(2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl)-3,5-dihydroxy-, (3R,5S,6E)-
• CAS NO: 147511-69-1
• Molecular Formula: C25H24FNO4
• Molecular Weight: 421.46
• Product Categories: API;LIVALO
• Mol File: 147511-69-1.mol
• Article Data: 16

Chemical Properties

• Boiling Point: 691.961 °C at 760 mmHg
• Flash Point: 372.285 °C
• Appearance: /
• Density: 1.352 g/cm³
• Vapor Pressure: 4.21E-20mmHg at 25°C
• Refractive Index: 1.679
• Storage Temp.: -20°C, Hygroscopic
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 4.24±0.10(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: Pitavastatin(CAS DataBase Reference)
• NIST Chemistry Reference: Pitavastatin(147511-69-1)
• EPA Substance Registry System: Pitavastatin(147511-69-1)

Safety Data

• Hazardous Substances Data: 147511-69-1(Hazardous Substances Data)

Usage

Description

Pitavastatin (Brand Name: LIVALO) is an inhibitor of HMG-CoA reductase which catalyzes the first step of cholesterol synthesis. It appears as odorless and white to pale-yellow powder. It takes effects by reducing the level of certain fatty substances such as cholesterol in the body. Therefore, it is mainly indicated for the treatment of hypercholesterolaemia and for the prevention of cardiovascular diseases. It can not only lower the high cholesterol and triglyceride in certain patients, but also can increase the content of high density lipoprotein (HDL), the “good” cholesterol levels. It should be generally administrated together with a proper diet.

Reference

https://en.wikipedia.org/wiki/Pitavastatin http://www.rxlist.com/livalo-drug.htm https://www.drugs.com/cdi/pitavastatin.html

Uses

HMGA reductase inhibitor

Definition

ChEBI: A hydroxy monocarboxylic acid anion that is the conjugate base of pitavastatin, obtained by deprotonation of the carboxy group.

Brand name

[Name previously used: Itavastatin].

Biological Activity

pitavastatin (nk-104) is a potent hmg-coa reductase inhibitor, pitavastatin inhibited cholesterol synthesis from acetic acid with an ic50 of 5.8 nm in a human liver cancer cell line (hepg2).

Enzyme inhibitor

This HMG-CoA reductase inhibitor (FW = 421.46 g/mol; CAS 147511-69- 1; IUPAC Name: (3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin- 3-yl]-3,5-dihydroxyhept-6-enoic acid), also known as itavastatin, itabavastin, nisvastatin, NK-104, NKS-104, and the trade name Livalo?, is indicated for ameliorating hypercholesterolemia and preventing cardiovascular disease. NK-104 potency is dose-dependent and is roughly equivalent to that of atorvastatin. It is well-tolerated in the treatment of patients with hypercholesterolemia. Pitavastatin uptake is carrier-mediated. Target(s): Reduces inflammatory cytokine production from human bronchial epithelial cells; Decreases microtubule tau protein levels via the inactivation of Rho/ROCK; Inhibits hepatic steatosis and fibrosis in non-alcoholic steatohepatitis model; Suppresses therosclerosis induced by chronic inhibition of the synthesis of nitric oxide in moderately hypercholesterolemic rabbits; Decreases the expression of endothelial lipase both in vitro and in vivo; Inhibits NFkB pathway in brain; Inactivates NFkB and decreases IL-6 production through Rho kinase pathway in MCF-7 human breast cancer cells; Reduces C-reactive-protein-induced interleukin-8 production in human aortic endothelial cells; Inhibits lysophosphatidic acid-induced proliferation and monocyte chemoattractant protein-1 expression in aortic smooth muscle cells by suppressing Rac-1-mediated reactive oxygen species generation; Inhibits upregulation of intermediate conductance calcium-activated potassium channels and coronary arteriolar remodeling induced by long-term blockade of nitric oxide synthesis; Inhibits migration and proliferation of rat vascular smooth muscle cells.

InChI:InChI=1/C25H24FNO4/c26-17-9-7-15(8-10-17)24-20-3-1-2-4-22(20)27-25(16-5-6-16)21(24)12-11-18(28)13-19(29)14-23(30)31/h1-4,7-12,16,18-19,28-29H,5-6,13-14H2,(H,30,31)/b12-11+

Upstream product

• 172336-32-2 (±)-E-3,5-dihydroxy-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-6-heptenoic acid ethyl ester 
• 1388627-65-3 2-((4R,6S)-6-((benzo[d]thiazol-2-ylsulfonyl)methyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetic acid methyl ester 
• 1885-29-6 anthranilic acid nitrile 
• 167073-19-0 (E)-(3R,5S)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dihydroxy-hept-6-enoic acid ethyl ester 
• 254452-89-6 (E)-(S)-5-[2-Cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3-hydroxy-pent-4-enoic acid (S)-2-hydroxy-1,2,2-triphenyl-ethyl ester 
• 254452-93-2 (E)-(R)-5-[2-Cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3-hydroxy-pent-4-enoic acid (R)-2-hydroxy-1,2,2-triphenyl-ethyl ester 
• 254452-91-0 ethyl 5(S)-(E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-quinolin-3-yl]-5-hydroxy-3-oxo-6-heptenoate 
• 254452-90-9 (E)-(S)-5-[2-Cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3-hydroxy-pent-4-enoic acid methyl ester 
• 254452-94-3 (E)-(R)-5-[2-Cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3-hydroxy-pent-4-enoic acid methyl ester 
• 256431-72-8 (E)-3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]-2-propenenitrile 
• 148901-68-2 (E)-3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-propenal 
• 121660-37-5 2-cyclopropyl-4-(4-fluorophenyl)-3-formylquinoline 
• 121660-11-5 2-cyclopropyl-4-(4-fluorophenyl)-3-(hydroxymethyl)quinoline 
• 380848-30-6 (E)7-[2-cyclopropyl-4-(4-fluorophenyl)-quinolin-3-yl]-(3S,5S)-dihydroxyhept-6-enic acid ethyl ester 

Downstream Products

• 167073-19-0 (E)-(3R,5S)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dihydroxy-hept-6-enoic acid ethyl ester 
• 141750-59-6 (3S,5R,6E)-7-<2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl>-3,5-dihydroxy-6-heptenoic acid ,15-lactone 

Relevant articles and documents

Method for preparing rosuvastatin and pitavastatin 2, 5-diene heptanoate compound

The invention discloses a method for preparing rosuvastatin and pitavastatin 2, 5-diene heptanoate compound. (4R, 6S)-6-[(1E)-2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl (methanesulfonyl)amino]-5-pyrimidine] vinyl]-2,2-dimethyl-1,3-dioxane-4-tert-butyl acetate and (4R, 6S)-6-[[(1E)-2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl] vinyl]-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate are respectivelytaken as starting materials of rosuvastatin and pitavastatin, deprotection and a hydrolyzation one-step method is adopted to prepare statin acid, then the statin acid is taken as a reaction substratefor dehydration and substitution two-step reaction to prepare the 2, 5-diene heptanoate compound. The preparation and synthesis routes of rosuvastatin and pitavastatin 2, 5-diene heptanoate involved in the invention are short and feasible, the operation is simple and convenient, the product yield is high, and the rosuvastatin and pitavastatin 2, 5-diene heptanoate is more suitable for large-scaleindustrial production.

For production of the precursor [...]

PROBLEM TO BE SOLVED: To provide a precursor compound of pitavastatin calcium excellent in safety and cost with high yield and high selectivity in a mild condition.SOLUTION: A method for producing a precursor compound of pitavastatin calcium of formula 1 is characterized by reacting a compound of formula 2 with a compound of formula 3 in the presence of an alkali metal salt selected from alkali metal carbonate, alkali metal acetate, and alkali metal propionate. (In the formulae, Ris a C-Calkyl group, and Ris an aryl group, an aralkyl group, or an alkyl group.)

The synthesis of [18F]pitavastatin as a tracer for hOATP using the Suzuki coupling

Fluorine-18 labeled radiotracers, such as [18F]fluorodeoxyglucose, can be used as practical diagnostic agents in positron emission tomography (PET). Furthermore, the properties of pharmaceuticals can be enhanced significantly by the introduction of fluorine groups into their original structures, and significant progress has been made during the last three decades towards the development of practical procedures for the introduction of fluorine. The replacement of the fluorine atoms present in pharmaceuticals with radioactive 18F atoms is a rational approach for designing novel PET tracers. As a fluorine-containing pharmaceutical agent, pitavastatin has attracted considerable interest from researchers working in the life sciences because it can act as an antihyperlipidemic agent as well as a substrate for hepatic organic anion transporting polypeptides (hOATP). With this in mind, it was envisaged that [18F]pitavastatin would be used as an excellent imaging agent for hOATP, which prompted us to investigate the synthesis of this agent. Herein, we report a practical method for the synthesis of [18F]pitavastatin by the Suzuki coupling reaction of p-iodofluorobenzene and a quinoline boronate derivative, with the desired product being formed in a radiochemical yield of 12 ± 3% (decay corrected from [18F]fluoride ions, n = 3). This journal is