Pitavastatin calcium

Base Information

• Chemical Name: Pitavastatin calcium
• CAS No.: 147526-32-7
• Deprecated CAS: 1187847-92-2
• Molecular Formula: (C25H23FNO4)2^.Ca
• Molecular Weight: 880.999
• Hs Code.: 29339900
• European Community (EC) Number: 643-092-3,807-641-2
• UNII: IYD54XEG3W
• DSSTox Substance ID: DTXSID4046448
• Wikipedia: Pitavastatin
• Wikidata: Q27139472
• NCI Thesaurus Code: C87752
• RXCUI: 861640
• ChEMBL ID: CHEMBL1237061
• Mol file: 147526-32-7.mol

Synonyms:(E,3R,5S)-7-(2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-3,5-dihydroxyhept-6-enoic acid;itavastatin;itavastatin calcium;nisvastatin;NK 104;NK-104;P 872441;P-872441;pitavastatin;pitavastatin calcium;pitavastatin lactone

Chemical Property of Pitavastatin calcium

Chemical Property:

• Appearance/Colour: white to off-white powder
• Boiling Point: 692 °C at 760 mmHg
• Flash Point: 372.3 °C
• PSA: 186.96000
• LogP: 6.36680
• Storage Temp.: 2-8°C
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 14
• Exact Mass: 880.2848136
• Heavy Atom Count: 63
• Complexity: 626

Purity/Quality:

99% ^*data from raw suppliers

Pitavastatin calcium ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC1C2=NC3=CC=CC=C3C(=C2C=CC(CC(CC(=O)[O-])O)O)C4=CC=C(C=C4)F.C1CC1C2=NC3=CC=CC=C3C(=C2C=CC(CC(CC(=O)[O-])O)O)C4=CC=C(C=C4)F.[Ca+2]
• Isomeric SMILES: C1C(C1)C2=NC3=CC=CC=C3C(=C2/C=C/[C@@H](O)C[C@@H](O)CC(=O)[O-])C4=CC=C(C=C4)F.C1C(C1)C2=NC3=CC=CC=C3C(=C2/C=C/[C@@H](O)C[C@@H](O)CC(=O)[O-])C4=CC=C(C=C4)F.[Ca+2]
• Recent ClinicalTrials: Safety and Efficacy Comparison Study of NK-104-CR (Controled Release) in Patients With Primary Hyperlipidemia or Mixed Dyslipidemia
• Recent EU Clinical Trials: A PHASE 3 STUDY EVALUATING THE EFFECT OF PITAVASTATIN TO PREVENT CARDIOVASCULAR EVENTS IN HIV-1 INFECTED INDIVIDUALS
• Recent NIPH Clinical Trials: Effectiveness of Ezetimibe or Pitavastatin calcium calcium in NASH/NAFLD patients with high cholesterol levels: a randomized controlled study
• Description: Pitavastatin, launched for the treatment of hypercholesterolemia, belongs to the family of second-generation statins, also referred to as superstatins due to their improved efficacy as cholesterol lowering agents. Like other statins, pitavastatin reduces plasma cholesterol levels by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis in the liver. It is a more potent inhibitor of HMG-CoA reductase than the previously marketed statins and has the potential benefit of not undergoing significant metabolism by CYP3A4. Pitavastatin is synthesized in a multi-step sequence, including the key step of introducing the dihydroxyheptenoate side chain by cross-coupling of a 3-iodoquinoline intermediate with an alkenylborane reagent. Unlike rosuvastatin, pitavastatin has a high oral bioavailability (～80%). Plasma protein binding is also high for pitavastatin (＞95%), and regardless of the dosing, the highest tissue levels are found in the liver, its target organ. After oral administration, the peak plasma concentration is reached at ,0.8 h and the mean elimination half-life is ～11 h. Pitavastatin is only minimally metabolized, mainly by CYP2C8 and CYP2C9, and the predominant route of elimination of the parent drug and its metabolites is by means of bile excretion followed by elimination in the feces. In clinical studies, oral doses of 2–4 mg/day of pitavastatin produced dose-dependent reduction in LDL-cholesterol levels by 40–48% from baseline in patients with heterozygous familial hypercholesterolemia. In a 12-week double-blind comparative study, pitavastatin (2 mg/day) was more effective than pravastatin (10 mg/day) in reducing LDL-cholesterol levels (38 and 18%, respectively); however, both agents produced similar increases in HDL-cholesterol (～9%). The drug was well tolerated and the adverse reactions were mild and transient.
• Uses: Pitavastatin calcium (Livalo) is a novel member of the medication class of statins A competitive inhibitor of HMG-CoA reductase. Antilipemic.

Technology Process of Pitavastatin calcium

There total 108 articles about Pitavastatin calcium which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

methyl (3R,5S,6E)-7-{2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl}-3,5-dihydroxyhept-6-enoate (849811-78-5) → pitavastatin (147526-32-7,147511-69-1,688735-41-3,769908-13-6,121659-03-8)

Guidance literature:

With sodium hydroxide; In methanol; at 20 ℃; for 0.5h;

DOI:10.1039/c4ob01953a

Reference yield: 95.9%

pitavastatin calcium salt (147526-32-7) → pitavastatin (147526-32-7,147511-69-1,688735-41-3,769908-13-6,121659-03-8)

Guidance literature:

With hydrogenchloride; In water; ethyl acetate; at 25 - 35 ℃;

Reference yield: 94.0%

(4R,6S)-(E)-{6-[2-(2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-vinyl]-2,2-dimethyl-1,3-dioxan-4-yl}acetic acid tert-butyl ester (147489-06-3) → pitavastatin (147526-32-7,147511-69-1,688735-41-3,769908-13-6,121659-03-8)

Guidance literature:

(4R,6S)-(E)-{6-[2-(2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-vinyl]-2,2-dimethyl-1,3-dioxan-4-yl}acetic acid tert-butyl ester; With trifluoroacetic acid; In acetonitrile; at 30 - 35 ℃;

With caesium carbonate; In acetonitrile; at 35 - 40 ℃;

upstream raw materials:

(±)-E-3,5-dihydroxy-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-6-heptenoic acid ethyl ester

2-cyclopropyl-4-(4-fluorophenyl)-3-(hydroxymethyl)quinoline

2-cyclopropyl-4-(4-fluorophenyl)-3-formylquinoline

(E)-3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-propenal

Downstream raw materials:

8-Hydroxypitavastatin

(3R,5S,E)-7-(2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-3,5-dihydroxyhept-6-enoic acid (R)-NEA salt

pitavastatin

pitavastatin piperidine

Refernces

• 1、 -. "Multi-substituted dihydroisoquinolines he the sandbank contains the fluorine derivative and use thereof". Paragraph 0135; 0136. . Retrieved 2018/06/04.
• 2、 Spreider, Pierre A.,Breit, Bernhard. "Palladium-Catalyzed Stereoselective Cyclization of in Situ Formed Allenyl Hemiacetals: Synthesis of Rosuvastatin and Pitavastatin". . p. 3286 - 3290. Retrieved 2018/06/11.