New Drug Approvals





Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 


Blog Stats

  • 4,242,594 hits

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 2,802 other subscribers

add to any





Atorvastatin (INN/əˌtɔrvəˈstætən/, marketed by Pfizer as a calcium salt under the trade name Lipitor,[1] is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammatory and other mechanisms. Like all statins, atorvastatin works by inhibitingHMG-CoA reductase, an enzyme found in liver tissue that plays a key role in production of cholesterol in the body.

Atorvastatin was first synthesized in 1985 by Bruce Roth of Parke-Davis Warner-Lambert Company (since acquired by Pfizer). The best selling drug in pharmaceutical history, sales of Lipitor since it was approved in 1996 exceed US$125 billion, and the drug has topped the list of best-selling branded pharmaceuticals in the world for nearly a decade.[2] When Pfizer’s patent on Lipitor expired on November 30, 2011,[3] generic atorvastatin became available in the United States, initially manufactured only by generic drugmakers Watson Pharmaceuticals and India’s Ranbaxy Laboratories. Prices for the generic version did not drop to the level of other generics—$10 or less for a month’s supply—until other manufacturers were able to supply the drug in May 2012.[4]

Atorvastatin calcium, YM-548, CI-981, Prevencor, Tahor, Lipibec, Torvast, Sortis, Lipitor
(3R,5R)-7-[2-(4-Fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrol-1-yl]-3,5-dihydroxyheptanoic acid calcium salt (2:1)
134523-03-8, 134523-00-5 (free acid), 110862-48-1 (free acid (R*,R*)-isomer)
Alzheimer’s Dementia, Treatment of , Cardiovascular Drugs, Cognition Disorders, Treatment of, Immunologic Neuromuscular Disorders, Treatment of, Lipoprotein Disorders, Treatment of , Metabolic Drugs, Multiple Sclerosis, Agents for, Neurologic Drugs, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, HMG-CoA Reductase Inhibitors, TNFSF6 Expression Inhibitors
Jouveinal (Originator), Pfizer (Originator), Almirall Prodesfarma (Licensee), Syncro (Licensee), Yamanouchi (Licensee), Stanford University (Codevelopment)
SYNTHESISTrans-6-[2-(3- or 4-carboxamido-substd. pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis
Roth, B.D. (Pfizer Inc.)
EP 0247633; US 4681893
1) The condensation of 2-(1,3-dixolan-2-yl)ethylamine (I) with ethyl 2-bromo-2-(4-fluorophenyl)acetate (II) by means of triethylamine in acetonitrile gives ethyl 2-[2-(1,3-dioxolan-2-yl)ethylamino]-2-(4-fluorophenyl)acetate (III), which is acylated with isobutyryl chloride (IV) and triethylamine in dichloromethane yielding the corresponding amide (V). Saponification of the ester (V) with NaOH in methanol/water affords the free acid (VI), which is cyclized with N,3-diphenylpropynamide (VII) [obtained in the reaction of 3-phenylpropynoic acid (VIII) with aniline (IX) by means of dicyclohexylcarbodiimide (DCC)] by heating at 90 C in acetic anhydride giving 1-[2-(1,3-dioxolan-2-yl)ethyl]-5-(4-fluorophenyl)-2-isopropyl-N,4-diphenylpyrrole-3-carboxamide (X). The hydrolysis of the dioxolane group of (X) with HCl yields the corresponding aldehyde (XI), which is condensed with methyl acetoacetate (XII) by means of NaH in THF affording 7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(N-phenylcarbamoyl)pyrrol-1-yl]-5-hydroxy-3-oxoheptanoic acid methyl ester (XIII). The reduction of the carbonyl group of (XIII) with tributylborane and NaBH4 in THF gives the (3R*,5R*)-dihydroxy ester (XIV), which is saponified with NaOH in water yielding the corresponding free acid (XV). The lactonization of (XV) by heating in refluxing toluene affords the (R*,R*)-lactone (XVI), which is submitted to optical resolution by reaction with (R)-1-phenylethylamine (XVII) followed by fractional crystallization thus obtaining the amide (XVII) as the pure (R,R,R)-enantiomer. The hydrolysis of the amide (XVIII) with NaOH, followed by heating in refluxing toluene gives the (R,R)-lactone (XIX), which is finally treated first with NaOH in methanol/water, and then with CaCl2 or calcium acetate.
  1. “Pfizer product promotion page (Liptor)”. Retrieved 2011-12-05.
  2. “Lipitor becomes world’s top-selling drug”. Crain’s New York Business. 2011-12-28.
  3. CNN Wire Staff (November 30, 2011). “Lipitor loses patent, goes generic”CNN. Retrieved November 18, 2012.
  4. NeLM, June 2012: Price to UK National Health Service for 28 tablets from £3.25 (10mg) to £10.00 (80mg).
  5. “Atorvastatin Calcium”. Retrieved 3 April 2011.

Further reading

External links

An improved synthesis of 1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, a key intermediate for atorvastatin synthesis
Radl, S.; et al.
Tetrahedron Lett 2002,43(11),2087
The 6-cyanohexanoic ester (VII), intermediate in the synthesis of 180072 (see intermediate (XLI) in scheme no. 18007204a) has been obtained as follows: the reaction of 1,6-heptadien-4-ol (I) with BuLi, CO2, and I2 in THF gives the cyclic carbonate (II), which is treated with Ts-OH in acetone to yield the acetonide (III). The reaction of the iodine atom of (III) with KCN in hot DMSO affords the nitrile (IV), which is oxidized at the terminal double bond with OsO4 and NaIO4, or O3 and Me2S, to provide the carbaldehyde (V). The oxidation of (V) with CrO3/H2SO4 in acetone gives the carboxylic acid (VI), which is finally esterified with tert-butanol by means of DCC and DMAP in dichloromethane, yielding the target ester intermediate (VII).

Lipitor industrial production shown below (TL, 1985, 2951; TL, 1992, 2279; 2283)

Divided into two fragments. Primary amine fragment iso-ascorbic acid as a starting material (stereoisomer of vitamin C) in the system. 1,4 – dione as a starting material isobutyrylacetanilide fragment, obtained by the Stetter reaction, the reaction of benzoin conjugated version Michael addition. Diketone related primary amine with a substituted pyrrole ring obtained five, after deprotection and salt formation Lipitor.

Atorvastatin of IC50-0.025μM, its RR configuration is as high IC50-0.007μM (SS configuration IC50-0.44μM).

Initially synthesized as shown above (JMC, 1991, 357).
Which polysubstituted pyrrole ring by the Munchnone of 1,3-dipolar [3 +2] cycloaddition get.

(atorvastatin), a part of statin (statins) a class of drugs.


  1. medchemnintabelle says:

    Reblogged this on MedCheminAustralia.

  2. saminakhan2001 says:

    Reblogged this on MEDCHEMEGYPT.

  3. Thanks a lot for sharing this with all people you actually recognise what you’re talking about!
    Bookmarked. Please additionally seek advice from my site =).

    We can have a link change agreement between us

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.


Follow New Drug Approvals on

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 2,802 other subscribers


DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, CLEANCHEM LABS as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

Personal Links

View Full Profile →



Follow my blog with Bloglovin The title of your home page You could put your verification ID in a comment Or, in its own meta tag Or, as one of your keywords Your content is here. The verification ID will NOT be detected if you put it here.
%d bloggers like this: