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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, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India 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

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Skeletal formula of colchicine


CAS Registry Number: 64-86-8CAS Name:N-[(7S)-5,6,7,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl]acetamideMolecular Formula: C22H25NO6Molecular Weight: 399.44

CSIR-Laxai Life Sciences get DCGI nod for clinical trials Colchicine on Covid patients


It is an important therapeutic intervention for Covid-19 patients with cardiac co-morbidities and also for reducing proinflammatory cytokines

The Council of Scientific & Industrial Research (CSIR), and Laxai Life Sciences Pvt. Ltd. Hyderabad, have obtained approval from the Drug Controller General of India (DCGI) to undertake a two-arm phase-II clinical trial of the drug Colchicine for Covid-19 treatment.

The partner CSIR institutes in this important clinical trial are the CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad and CSIR-Indian Institute of Integrative Medicine (IIIM), Jammu.

According to Ram Vishwakarma, advisor to DG-CSIR, colchicine, in combination with standard of care, will be an important therapeutic intervention for Covid-19 patients with cardiac co-morbidities and also for reducing proinflammatory cytokines, leading to faster recovery.

A number of global studies have confirmed now that cardiac complications during the course of Covid-19 infections and post-covid syndrome are leading to the loss of many lives, and it is essential to look for new or repurposed drugs.




A visionary & an entrepreneur with 17 years of experience in technology and bio-pharma industries. Founder and ex-CEO of LAXAI Pharma Ltd – a clinical data services company based in NJ, USA. Past employment: Pfizer, Wyeth Pharmaceuticals, Johnson & Johnson and Deloitte.

Vamsi provides a unique blend of operational and financial experience – along with a strong and expansive network of key influencers, industry experts and financial partners. He delivers a visionary understanding of client challenges and opportunities, and the instinctive ability to facilitate collaboration between the right people to turn strategic concepts into actionable plans – and, ultimately, into business results.

Dr S Chandrasekhar (Director CSIR-IICT, Hyderabad) and Dr. DS Reddy (Director, CSIR-IIIM, Jammu), the two partner institutes from CSIR said that they were looking forward to the outcome of this Phase II clinical efficacy trial on Colchicine, which may lead to life-saving intervention in the management of hospitalised patients.


Dr S Chandrasekhar (Director CSIR-IICT, Hyderabad)


Dr. DS Reddy (Director, CSIR-IIIM, Jammu)

India is one of the largest producers of this key drug and if successful, it will be made available to the patients at an affordable cost.

According to Ram Upadhayay, CEO, Laxai the enrollment of patients has already begun at multiple sites across India and the trial is likely to be completed in the next 8-10 weeks.

The drug can be made available to the large population of India based on the results of this trial and regulatory approval, he added.

Recent clinical studies have reported in leading medical journals about colchicine being associated with a significant reduction in the rates of recurrent pericarditis, post-pericardiotomy syndrome, and peri-procedural atrial fibrillation following cardiac surgery and atrial fibrillation ablation, according to a release.


Ram Upadhayaya, PhD

Chief Executive Officer, LAXAI

Ram Upadhayaya, CEO of Laxai Life Sciences, brings with him more than two decades of R&D experience spanning both academia and industry. A Ph. D in synthetic organic Chemistry, Ram has held key positions with leading international drug discovery organizations such as Bioimics AB Sweden, and Lupin India. Apart from his industrial background, Ram has been deeply associated with academic research. He was associated with Institute of Molecular Medicine, India as Principal Scientist as well as Uppsala University, Sweden in the capacity of Assistant Professor (Forskare). During these stints he significantly contributed to the development of novel therapeutics against infectious diseases such as AIDS and TB.

Ram has 10 international patents to his credit and has authored 25 peer reviewed publications. He is concurrently a consultant to the scientific advisory committee of the Principal Scientific Advisor, Government of India.

Raghava Reddy Kethiri, PhD, LAXAI
Chief Scientific Officer

25+ years of experience at various leadership positions in Biotech, CRO and Universities; Ex Karlsruhe Institute of Technology (KIT), Technical University of Dresden (TUD), JADO Technologies , Dresden, Germany, Jubilant Biosys, India

Delivered several leads, optimised leads and PCCs/DCs across Oncology, Pain, CNS, MD and Antibacterial therapeutics areas for global pharmaceutical companies. Co-Inventor of two clinical candidates ASN-001 ( NCT 02349139) for Metastatic Castration Resistant Prostrate Cancer & ASN-007 (NCT 03415126) for metastatic KRAS, NRAS & HRAS mutated solid tumors. Co-authored over 60 publications/patents (US/EU/Indian)


CAS Registry Number: 64-86-8

CAS Name:N-[(7S)-5,6,7,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl]acetamideMolecular Formula: C22H25NO6Molecular Weight: 399.44Percent Composition: C 66.15%, H 6.31%, N 3.51%, O 24.03%

Literature References: A major alkaloid of Colchicum autumnale L., Liliaceae. Extraction procedure: Chemnitius, J. Prakt. Chem. [II] 118, 29 (1928); F. E. Hamerslag, Technology and Chemistry of Alkaloids (New York, 1950) pp 66-80. Structure: Dewar, Nature155, 141 (1945); King et al.,Acta Crystallogr.5, 437 (1952); Horowitz, Ullyot, J. Am. Chem. Soc.74, 487 (1952). Crystal structure: L. Lessinger, T. N. Margulis, Acta Crystallogr.B34, 578 (1978). 
Total synthesis: Schreiber et al.,Helv. Chim. Acta44, 540 (1961); Van Tamelen et al.,Tetrahedron14, 8 (1961); Nakamura, Chem. Pharm. Bull.8, 843 (1960); Sunagawa et al.,ibid.9, 81 (1961); 10, 281 (1962); Scott et al.,Tetrahedron21, 3605 (1965); Woodward, Harvey Lectures, Ser. 59 (Academic Press, New York, 1965) p 31; Kotani et al.,Chem. Commun.1974, 300; D. A. Evans et al.,J. Am. Chem. Soc.103, 5813 (1981). 
Biosynthesis: Leete, Tetrahedron Lett.1965, 333; Battersby et al.,J. Chem. Soc.1964, 4257; Hill, Unrau, Can. J. Chem.43, 709 (1965). Tubulin-binding activity: J. M. Andreu, S. N. Timasheff, Proc. Natl. Acad. Sci. USA79, 6753 (1982). Toxicity: S. J. Rosenbloom, F. C. Ferguson, Toxicol. Appl. Pharmacol.13, 50 (1968); R. P. Beliles, ibid.23, 537 (1972). Clinical evaluations in cirrhosis of the liver: M. M. Kaplan et al.,N. Engl. J. Med.315, 1448 (1986); D. Kershenobich et al.,ibid.318, 1709 (1988). Bibliography of early literature: Eigsti, Lloydia10, 65 (1947). 
Monograph: O. J. Eigsti, P. Dustin, Jr., Colchicine in Agriculture, Medicine, Biology and Chemistry (Iowa State College Press, Ames, Iowa, 1955). Reviews: Fleming, Selected Organic Syntheses (John Wiley, London, 1973) pp 183-207; G. Lagrue et al.,Ann. Med. Interne132, 496-500 (1981); F. D. Malkinson, Arch. Dermatol.118, 453-457 (1982). Comprehensive description: D. K. Wyatt et al.,Anal. Profiles Drug Subs.10, 139-182 (1981). 
Properties: Pale yellow scales or powder, mp 142-150°. Darkens on exposure to light. Has been crystallized from ethyl acetate, pale yellow needles, mp 157°. [a]D17 -429° (c = 1.72). [a]D17 -121° (c = 0.9 in chloroform). pK at 20°: 12.35; pH of 0.5% soln: 5.9. uv max (95% ethanol): 350.5, 243 nm (log e 4.22; 4.47). One gram dissolves in 22 ml water, 220 ml ether, 100 ml benzene; freely sol in alcohol or chloroform. Practically insol in petr ether. Forms two cryst compds with chloroform, B.CHCl3 or B.2CHCl3, which do not give up their chloroform unless heated between 60 and 70° for considerable time. LD50 in rats (mg/kg): 1.6 i.v. (Rosenbloom, Ferguson); in mice (mg/kg): 4.13 i.v. (Beliles).

Melting point: mp 142-150°; mp 157°pKa: pK at 20°: 12.35; pH of 0.5% soln: 5.9Optical Rotation: [a]D17 -429° (c = 1.72); [a]D17 -121° (c = 0.9 in chloroform)Absorption maximum: uv max (95% ethanol): 350.5, 243 nm (log e 4.22; 4.47)

Toxicity data: LD50 in rats (mg/kg): 1.6 i.v. (Rosenbloom, Ferguson); in mice (mg/kg): 4.13 i.v. (Beliles)Use: In research in plant genetics (for doubling chromosomes).Therap-Cat: Gout suppressant. Treatment of Familial Mediterranean Fever.Therap-Cat-Vet: Has been used as an antineoplastic.Keywords: Antigout.


DOI: 10.1039/C39740000300

DOI: 10.1002/hlca.19610440225 DOI: 10.1021/ja00409a032

File:Colchicine synthesis.svg


Here, we describe a concise, enantioselective, and scalable synthesis of (−)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid 23 exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC50 = ∼3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.

Graphical abstract: Enantioselective total synthesis of (−)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids

Enantioselective total synthesis of (−)- and (+)-colchicine

The synthesis began with the transition-metal-catalyzed C–H bond functionalization of 7 with 14 (Scheme 1). Inspired by Li’s seminal work,18 we applied the strategy to compound 7. Pleasingly, after optimization, we successfully generated the N-sulfonyl imine in situ by reaction of 7 with TsNH2 (15) in the presence of anhydrous CuSO4 in THF. Furthermore, subsequent treatment of this imine with [RhCp*Cl2]2 (1 mol%), AgSbF6 (4 mol%), NaOAc (2.0 equiv.), and 14 (2.0 equiv.) at 80 °C afforded ortho-olefinated benzaldehyde 16 in good yield (90% on a 0.5 g scale; 70% on a 5.0 g scale). This modified catalytic C–H bond activation involved a transient directing group.19

Scheme 1 Enantioselective synthesis of (−)-colchicine and (+)-colchicine.


Recently one of my relatives have fallen ill and was prescribed with some colchicine. Looking at the structure of the molecule, and with nothing much to do, I decided to put my retrosynthetic skills to the test. Here is a picture of my thought process: 

Is there a better way to design a synthesis for this compound using the disconnection method.

From 11b, a Birch reduction is carried out to give the qunione 10b. A rearrangement of the ketone with methanediazonium gives 9b. A dihydroxylation with a peroxy acid and subsequent addition of water gives 8b. A double dehydration reaction with sulfuric acid, coupled with the protection of the ketone with propan-1,3-diol gives the seven-membered quinone 7b. A Heck reaction (or Ullmann reaction) with 7a with a palladium catalyst yields 6. (The protection group is thereafter labelled “PG”) Friedel-Crafts acylation with ethanoyl chloride yields 5 (although on second thoughts, I should have done the acylation from 7a from the start). A Michael addition is then carried out with BuLiBuLi to lithiate the ketone to give the terminal imine 4. Since this terminal imine is unstable, a mild reducing agent converts the imine to the amine 3. The ketone is then removed by addition of dithiol and subsequently reduced by Raney nickel to form 2. Finally, a simple condensation reaction between the amine and acetic anhydride, followed by deprotection of the ketone using an acid, yields the final product colchicine, 1.

Colchicine is a medication used to treat gout[1][2] and Behçet’s disease.[3] In gout, it is less preferred to NSAIDs or steroids.[1] Other uses for colchicine include the management of pericarditis and familial Mediterranean fever.[1][4] Colchicine is taken by mouth.[1]

Colchicine has a narrow therapeutic index and overdosing is therefore a significant risk. Common side effects of colchicine include gastrointestinal upset, particularly at high doses.[5] Severe side effects may include low blood cells and rhabdomyolysis, and the medication can be deadly in overdose.[1] It is not clear whether colchicine is safe for use during pregnancy, but its use during breastfeeding appears to be safe.[1][6] Colchicine works by decreasing inflammation via multiple mechanisms.[7]

Colchicine, in the form of the autumn crocus (Colchicum autumnale), has been used as early as 1500 BC to treat joint swelling.[8] It was approved for medical use in the United States in 1961.[9] It is available as a generic medication in the United Kingdom.[6] In 2017, it was the 201st-most commonly prescribed medication in the United States, with more than two million prescriptions.[10][11]

Medical uses


Colchicine is an alternative for those unable to tolerate NSAIDs in gout.[12] At high doses, side effects (primarily gastrointestinal upset) limit its use.[13][14] At lower doses, it is well tolerated.[13][15][16][17] One review found low-quality evidence that low-dose colchicine (1.8 mg in one hour or 1.2 mg per day) reduced gout symptoms and pain, whereas high-dose colchicine (4.8 mg over 6 hours) was effective against pain, but caused more severe side effects, such as diarrhea, nausea or vomiting.[16]

For treating gout symptoms, colchicine is used orally with or without food, as symptoms first appear.[18] Subsequent doses may be needed if symptoms worsen.[18][16] There is preliminary evidence that daily colchicine (0.6 mg twice daily) was effective as a long-term prophylaxis when used with allopurinol to reduce the risk of increased uric acid levels and acute gout flares,[2] although adverse gastrointestinal effects may occur.[19]

Other conditions

Colchicine is also used as an anti-inflammatory agent for long-term treatment of Behçet’s disease.[20] It appears to have limited effect in relapsing polychondritis, as it may only be useful for the treatment of chondritis and mild skin symptoms.[21] It is a component of therapy for several other conditions, including pericarditis, pulmonary fibrosis, biliary cirrhosis, various vasculitides, pseudogout, spondyloarthropathies, calcinosis, scleroderma, and amyloidosis.[20][22][23] Research regarding the efficacy of colchicine in many of these diseases has not been performed.[23] It is also used in the treatment of familial Mediterranean fever,[20] in which it reduces attacks and the long-term risk of amyloidosis.[24]

Colchicine is effective for prevention of atrial fibrillation after cardiac surgery.[25] Potential applications for the anti-inflammatory effect of colchicine have been studied with regard to atherosclerosis and chronic coronary disease (e.g., stable ischemic heart disease).[26] In people with recent myocardial infarction (recent heart attack), it has been found to reduce risk of future cardiovascular events. Its clinical use may grow to include this indication.[27][28]

Colchicine is also being studied in clinical trials for possible effects on COVID-19.[29][30]


Long-term (prophylactic) regimens of oral colchicine are absolutely contraindicated in people with advanced kidney failure (including those on dialysis).[18] About 10-20 percent of a colchicine dose is excreted unchanged by the kidneys; it is not removed by hemodialysis. Cumulative toxicity is a high probability in this clinical setting, and a severe neuromyopathy may result. The presentation includes a progressive onset of proximal weakness, elevated creatine kinase, and sensorimotor polyneuropathy. Colchicine toxicity can be potentiated by the concomitant use of cholesterol-lowering drugs.[18]

Adverse effects

Deaths – both accidental and intentional – have resulted from overdose of colchicine.[18] Typical side effects of moderate doses may include gastrointestinal upset, diarrhea, and neutropenia.[13] High doses can also damage bone marrow, lead to anemia, and cause hair loss. All of these side effects can result from inhibition of mitosis,[31] which may include neuromuscular toxicity and rhabdomyolysis.[18]


According to one review, colchicine poisoning by overdose (range of acute doses of 7 to 26 mg) begins with a gastrointestinal phase occurring 10–24 hours after ingestion, followed by multiple organ dysfunction occurring 24 hours to 7 days after ingestion, after which the affected person either declines into multi-organ failure or recovers over several weeks.[32]

Colchicine can be toxic when ingested, inhaled, or absorbed in the eyes.[13] Colchicine can cause a temporary clouding of the cornea and be absorbed into the body, causing systemic toxicity. Symptoms of colchicine overdose start 2 to 24 hours after the toxic dose has been ingested and include burning in the mouth and throat, fevervomitingdiarrhea, and abdominal pain.[18] This can cause hypovolemic shock due to extreme vascular damage and fluid loss through the gastrointestinal tract, which can be fatal.[32][33]

If the affected person survives the gastrointestinal phase of toxicity, they may experience multiple organ failure and critical illness. This includes kidney damage, which causes low urine output and bloody urinelow white blood cell counts that can last for several days; anemia; muscular weakness; liver failurehepatomegalybone marrow suppressionthrombocytopenia; and ascending paralysis leading to potentially fatal respiratory failure. Neurologic symptoms are also evident, including seizuresconfusion, and delirium; children may experience hallucinations. Recovery may begin within six to eight days and begins with rebound leukocytosis and alopecia as organ functions return to normal.[32][31]

Long-term exposure to colchicine can lead to toxicity, particularly of the bone marrowkidney, and nerves. Effects of long-term colchicine toxicity include agranulocytosis, thrombocytopenia, low white blood cell counts, aplastic anemia, alopecia, rashpurpuravesicular dermatitiskidney damageanuriaperipheral neuropathy, and myopathy.[31]

No specific antidote for colchicine is known, but supportive care is used in cases of overdose. In the immediate period after an overdose, monitoring for gastrointestinal symptoms, cardiac dysrhythmias, and respiratory depression is appropriate,[31] and may require gastrointestinal decontamination with activated charcoal or gastric lavage.[32][33]

Mechanism of toxicity

With overdoses, colchicine becomes toxic as an extension of its cellular mechanism of action via binding to tubulin.[32] Cells so affected undergo impaired protein assembly with reduced endocytosisexocytosiscellular motility, and interrupted function of heart cells, culminating in multi-organ failure.[7][32]


In the United States, there are several hundred recorded cases of colchicine toxicity annually; approximately 10% of which end with serious morbidity or mortality. Many of these cases are intentional overdoses, but others were accidental; for example, if the drug was not dosed appropriately for kidney function. Most cases of colchicine toxicity occur in adults. Many of these adverse events resulted from the use of intravenous colchicine.[23]

Drug interactions

Colchicine interacts with the P-glycoprotein transporter, and the CYP3A4 enzyme involved in drug and toxin metabolism.[18][32] Fatal drug interactions have occurred when colchicine was taken with other drugs that inhibit P-glycoprotein and CYP3A4, such as erythromycin or clarithromycin.[18]

People taking macrolide antibioticsketoconazole or cyclosporine, or those who have liver or kidney disease, should not take colchicine, as these drugs and conditions may interfere with colchicine metabolism and raise its blood levels, potentially increasing its toxicity abruptly.[18][32] Symptoms of toxicity include gastrointestinal upset, fever, muscle painlow blood cell counts, and organ failure.[13][18] People with HIV/AIDS taking atazanavirdarunavirfosamprenavirindinavirlopinavirnelfinavirritonavir, or saquinavir may experience colchicine toxicity.[18] Grapefruit juice and statins can also increase colchicine concentrations.[18]

In gout, inflammation in joints results from the precipitation of circulating uric acid, exceeding its solubility in blood and depositing as crystals of monosodium urate in and around synovial fluid and soft tissues of joints.[7] These crystal deposits cause inflammatory arthritis, which is initiated and sustained by mechanisms involving various proinflammatory mediators, such as cytokines.[7] Colchicine accumulates in white blood cells and affects them in a variety of ways: decreasing motility, mobilization (especially chemotaxis) and adhesion.[23]

Under preliminary research are various mechanisms by which colchicine may interfere with gout inflammation:

Generally, colchicine appears to inhibit multiple proinflammatory mechanisms, while enabling increased levels of anti-inflammatory mediators.[7] Apart from inhibiting mitosis, colchicine inhibits neutrophil motility and activity, leading to a net anti-inflammatory effect, which has efficacy for inhibiting or preventing gout inflammation.[7][18]

The plant source of colchicine, the autumn crocus (Colchicum autumnale), was described for treatment of rheumatism and swelling in the Ebers Papyrus (circa 1500 BC), an Egyptian medical papyrus.[34] It is a toxic alkaloid and secondary metabolite.[13][35][18] Colchicum extract was first described as a treatment for gout in De Materia Medica by Pedanius Dioscorides, in the first century AD. Use of the bulb-like corms of Colchicum to treat gout probably dates to around 550 AD, as the “hermodactyl” recommended by Alexander of TrallesColchicum corms were used by the Persian physician Avicenna, and were recommended by Ambroise Paré in the 16th century, and appeared in the London Pharmacopoeia of 1618.[36][23] Colchicum use waned over time, likely due to the severe gastrointestinal side effects preparations caused. In 1763, Colchicum was recorded as a remedy for dropsy (now called edema) among other illnesses.[23] Colchicum plants were brought to North America by Benjamin Franklin, who had gout himself and had written humorous doggerel about the disease during his stint as United States Ambassador to France.[37]

Colchicine was first isolated in 1820 by the French chemists P. S. Pelletier and J. B.Caventou.[38] In 1833, P. L. Geiger purified an active ingredient, which he named colchicine.[39] It quickly became a popular remedy for gout.[23] The determination of colchicine’s structure required decades, although in 1945, Michael Dewar made an important contribution when he suggested that, among the molecule’s three rings, two were seven-member rings.[40] Its pain-relieving and anti-inflammatory effects for gout were linked to its ability to bind with tubulin.

An unintended consequence of the 2006 U.S. Food and Drug Administration (FDA) safety program called the Unapproved Drugs Initiative—through which the FDA sought more rigorous testing of efficacy and safety of colchicine and other unapproved drugs[41]—was a price increase of 2000 percent [42] for “a gout remedy so old that the ancient Greeks knew about its effects.”[42] Under Unapproved Drugs Initiative small companies like URL Pharma, a Philadelphia drugmaker, were rewarded with licenses for testing of medicines like colchicine. In 2009, the FDA reviewed a New Drug Application for colchicine submitted by URL Pharma. URL Pharma did the testing, gained FDA formal approval, and was granted rights over colchicine. With this monopoly pricing power, the price of colchicine increased.

In 2012 Asia’s biggest drugmaker, Takeda Pharmaceutical Co., acquired URL Pharma for $800 million including the rights to colchicine (brand name Colcrys) earning $1.2 billion in revenue by raising the price even more.[42]

Oral colchicine had been used for many years as an unapproved drug with no FDA-approved prescribing information, dosage recommendations, or drug interaction warnings.[43] On July 30, 2009, the FDA approved colchicine as a monotherapy for the treatment of three different indications (familial Mediterranean fever, acute gout flares, and for the prophylaxis of gout flares[43]), and gave URL Pharma a three-year marketing exclusivity agreement[44] in exchange for URL Pharma doing 17 new studies and investing $100 million into the product, of which $45 million went to the FDA for the application fee. URL Pharma raised the price from $0.09 per tablet to $4.85, and the FDA removed the older unapproved colchicine from the market in October 2010, both in oral and intravenous forms, but allowed pharmacies to buy up the older unapproved colchicine.[45] Colchicine in combination with probenecid has been FDA-approved before 1982.[44]

July 29, 2009, colchicine won FDA approval in the United States as a stand-alone drug for the treatment of acute flares of gout and familial Mediterranean fever.[46][47] It had previously been approved as an ingredient in an FDA-approved combination product for gout. The approval was based on a study in which two doses (1.2 mg and 0.6 mg) an hour apart were as effective as higher doses in combating the acute flare of gout.[17]

As a drug antedating the FDA, colchicine was sold in the United States for many years without having been reviewed by the FDA for safety and efficacy. The FDA reviewed approved colchicine for gout flares, awarding Colcrys a three-year term of market exclusivity, prohibiting generic sales, and increasing the price of the drug from $0.09 to $4.85 per tablet.[48][49][50]

Numerous consensus guidelines, and previous randomized controlled trials, had concluded that colchicine is effective for acute flares of gouty arthritis. However, as of 2006, the drug was not formally approved by the FDA, owing to the lack of a conclusive randomized control trial (RCT). Through the Unapproved Drugs Initiative, the FDA sought more rigorous testing of the efficacy and safety of colchicine and other unapproved drugs.[41] In exchange for paying for the costly testing, the FDA gave URL Pharma three years of market exclusivity for its Colcrys brand,[51] under the Hatch-Waxman Act, based in part on URL-funded research in 2007, including pharmacokinetic studies and a randomized control trial with 185 patients with acute gout.

In April 2010, an editorial in the New England Journal of Medicine said that the rewards of this legislation are not calibrated to the quality or value of the information produced, that no evidence of meaningful improvement to public health was seen, and that it would be less expensive for the FDA, the National Institutes of Health or large insurers to pay for trials themselves. Furthermore, the cost burden of this subsidy falls primarily on patients or their insurers.[52] In September 2010, the FDA ordered a halt to marketing unapproved single-ingredient oral colchicine.[53]

Colchicine patents expire on February 10, 2029.[54]

URL Pharma also received seven years of market exclusivity for Colcrys in the treatment of familial Mediterranean fever, under the Orphan Drug Law. URL Pharma then raised the price per tablet from $0.09 to $4.85 and sued to remove other versions from the market, increasing annual costs for the drug to U.S. state Medicaid programs from $1 million to $50 million. Medicare also paid significantly higher costs, making this a direct money-loser for the government. (In a similar case, thalidomide was approved in 1998 as an orphan drug for leprosy and in 2006 for multiple myeloma.)[52]


It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002) and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.[55]

Formulations and dosing

Trade names for colchicine are Colcrys or Mitigare which are manufactured as a dark– and light-blue capsule having a dose of 0.6 mg.[18][56] Colchicine is also prepared as a white, yellow, or purple pill (tablet) having a dose of 0.6 mg.[56]

Colchicine is typically prescribed to mitigate or prevent the onset of gout, or its continuing symptoms and pain, using a low-dose prescription of 0.6 to 1.2 mg per day, or a high-dose amount of up to 4.8 mg in the first 6 hours of a gout episode.[5][18][16] With an oral dose of 0.6 mg, peak blood levels occur within one to two hours.[35] For treating gout, the initial effects of colchicine occur in a window of 12 to 24 hours, with a peak within 48 to 72 hours.[18] It has a narrow therapeutic window, requiring monitoring of the subject for potential toxicity.[18] Colchicine is not a general pain relief drug, and is not used to treat pain in other disorders.[18]


According to laboratory research, the biosynthesis of colchicine involves the amino acids phenylalanine and tyrosine as precursors. Giving radioactive phenylalanine-2-14C to C. byzantinum, another plant of the family Colchicaceae, resulted in its incorporation into colchicine.[57] However, the tropolone ring of colchicine resulted from the expansion of the tyrosine ring. Radioactive feeding experiments of C. autumnale revealed that colchicine can be synthesized biosynthetically from (S)-autumnaline. That biosynthesic pathway occurs primarily through a phenolic coupling reaction involving the intermediate isoandrocymbine. The resulting molecule undergoes O-methylation directed by S-adenosylmethionine. Two oxidation steps followed by the cleavage of the cyclopropane ring leads to the formation of the tropolone ring contained by N-formyldemecolcine. N-formyldemecolcine hydrolyzes then to generate the molecule demecolcine, which also goes through an oxidative demethylation that generates deacetylcolchicine. The molecule of colchicine appears finally after addition of acetyl-coenzyme A to deacetylcolchicine.[58][59]



Colchicine may be purified from Colchicum autumnale (autumn crocus) or Gloriosa superba (glory lily). Concentrations of colchicine in C. autumnale peak in the summer, and range from 0.1% in the flower to 0.8% in the bulb and seeds.[23]

Colchicine is widely used in plant breeding by inducing polyploidy in plant cells to produce new or improved varieties, strains and cultivars.[60] When used to induce polyploidy in plants, colchicine cream is usually applied to a growth point of the plant, such as an apical tip, shoot, or sucker. Seeds can be presoaked in a colchicine solution before planting. Since chromosome segregation is driven by microtubules, colchicine alters cellular division by inhibiting chromosome segregation during meiosis; half the resulting gametes, therefore, contain no chromosomes, while the other half contains double the usual number of chromosomes (i.e., diploid instead of haploid, as gametes usually are), and lead to embryos with double the usual number of chromosomes (i.e., tetraploid instead of diploid).[60] While this would be fatal in most higher animal cells, in plant cells it is not only usually well-tolerated, but also frequently results in larger, hardier, faster-growing, and in general more desirable plants than the normally diploid parents. For this reason, this type of genetic manipulation is frequently used in breeding plants commercially.[60]

When such a tetraploid plant is crossed with a diploid plant, the triploid offspring are usually sterile (unable to produce fertile seeds or spores), although many triploids can be propagated vegetatively. Growers of annual triploid plants not readily propagated vegetatively cannot produce a second-generation crop from the seeds (if any) of the triploid crop and need to buy triploid seed from a supplier each year. Many sterile triploid plants, including some trees, and shrubs, are becoming increasingly valued in horticulture and landscaping because they do not become invasive species and will not drop undesirable fruit and seed litter. In certain species, colchicine-induced triploidy has been used to create “seedless” fruit, such as seedless watermelons (Citrullus lanatus). Since most triploids do not produce pollen themselves, such plants usually require cross-pollination with a diploid parent to induce seedless fruit production.

The ability of colchicine to induce polyploidy can be also exploited to render infertile hybrids fertile, for example in breeding triticale (× Triticosecale) from wheat (Triticum spp.) and rye (Secale cereale). Wheat is typically tetraploid and rye diploid, with their triploid hybrid infertile; treatment of triploid triticale with colchicine gives fertile hexaploid triticale.[61]


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Further reading

  • Dowd, Matthew J. (April 30, 1998). “Colchicine”. Virginia Commonwealth University. Archived from the original on 2010-06-10.
Clinical data
Trade namesColcrys, Mitigare, others
License dataUS DailyMedColchicine
Routes of
By mouth
ATC codeM04AC01 (WHO)
Legal status
Legal statusAU: S4 (Prescription only)CA℞-onlyUK: POM (Prescription only)US: ℞-only
Pharmacokinetic data
Protein binding35-44%
MetabolismMetabolism, partly by CYP3A4
Elimination half-life26.6-31.2 hours
ExcretionFaeces (65%)
showIUPAC name
CAS Number64-86-8 
PubChem CID6167
CompTox Dashboard (EPA)DTXSID5024845 DTXSID20274387, DTXSID5024845 
ECHA InfoCard100.000.544 
Chemical and physical data
Molar mass399.437 g·mol−1
3D model (JSmol)Interactive image

///////////Colchicine, CSIR, Laxai Life Sciences, DCGI, clinical trials,  Covid patients, covid 19, corona virus 





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4H-1-Benzopyran-4-one, 2-[2-(2,6-dichlorophenyl)ethenyl]-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methyl-4-piperidinyl]-

Molecular Weight






CSIR-IIIM Jammu has filed an IND Application of “IIIM-290” to Drug Controller General of India for conducting Phase I/Phase II clinical trial of its capsule formulation in patients with locally advanced or metastatic pancreatic cancer. This IND candidate has emerged from the eight years of medicinal chemistry/ preclinical efforts of IIIM Jammu in the area of small molecule kinase inhibitors. IIIM-290 (NCE) is an orally bioavailable CDK inhibitor, obtained via semisynthetic modification of a natural product rohitukine. Institute has already secured a patent on this small molecule as well as on its oral capsule formulation.

IIIM-290 is a potent and oral CDK inhibitor with IC50s of 90 and 94 nM for CDK2/A and CDK9/T1.

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Image result for iiim 290

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Discovery and Preclinical Development of IIIM-290, an Orally Active Potent Cyclin-Dependent Kinase Inhibitor

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Cite this: J. Med. Chem. 2018, 61, 4, 1664-1687


Abstract Image

Rohitukine (1), a chromone alkaloid isolated from Indian medicinal plant Dysoxylum binectariferum, has inspired the discovery of flavopiridol and riviciclib, both of which are bioavailable only via intravenous route. With the objective to address the oral bioavailability issue of this scaffold, four series of rohitukine derivatives were prepared and screened for Cdk inhibition and cellular antiproliferative activity. The 2,6-dichloro-styryl derivative IIIM-290 (11d) showed strong inhibition of Cdk-9/T1 (IC50 1.9 nM) kinase and Molt-4/MIAPaCa-2 cell growth (GI50 < 1.0 μM) and was found to be highly selective for cancer cells over normal fibroblast cells. It inhibited the cell growth of MIAPaCa-2 cells via caspase-dependent apoptosis. It achieved 71% oral bioavailability with in vivo efficacy in pancreatic, colon, and leukemia xenografts at 50 mg/kg, po. It did not have CYP/efflux-pump liability, was not mutagenic/genotoxic or cardiotoxic, and was metabolically stable. The preclinical data presented herein indicates the potential of 11d for advancement in clinical studies.




InventorRam A. VishwakarmaSandip B. BharateShashi BhushanDilip M. MondheShreyans K. JainSamdarshi MeenaSantosh K. GuruAnup S. PathaniaSuresh KumarAkanksha BehlMubashir J. MintooSonali S. BharatePrashant Joshi Current Assignee Council of Scientific and Industrial Research (CSIR)

The disruption of any internal and external regulation of cellular growth leads to tumorogenesis by uncontrolled proliferation. This loss of control occurs at multiple levels in most of the cancer cases. Cyclin-dependent kinases (CDKs) have been recognized as key regulators of cell cycle progression. Alteration and deregulation of CDK activity have pathogenic link to the cancer. Number of cancers are associated with hyper-activation of CDKs as a result of mutation of the CDK genes or CDK inhibitor genes. Therefore, CDK inhibitors or modulators are of great interest to explore as novel therapeutic agents against cancer (Senderowicz, A. M. Leukemia 2001, 15, 1). Several classes of chemical inhibitors of CDK activity have been described (Zhang, J. et. al. Nat Rev Cancer. 2009, 9, 28) and some of them have reached to clinical pipeline for cancer.

Because CDK inhibitors are ATP competitive ligands; hence earlier they were typically described as purine class of compounds for example dimethylaminopurine, a first substance to be known as a CDK inhibitor (Neant, I. et al. Exp. Cell Res. 1988, 176, 68), olomoucine (Vesely, J. et al. Eur. J. Biochem. 1994, 224, 771) and roscovitine (Meijer, L. et al. Eur. J. Biochem. 1997, 243, 527). The IC50values of these purine class of compounds for CDK1/cyclin B are 120, 7 and 0.2-0.8 μM respectively (Gray, N. et al. Curr. Med. Chem. 1999, 6, 859). Some of the more potent members of this series have been prepared by the Schultz group using combinatorial approaches (Gray, N. S. et al. Science 1998, 281, 533). Number of synthetic flavoalkaloids having potent CDK inhibitory activity has been reviewed recently (Jain, S. K. et al. MiniRev. Med. Chem. 2012, 12, 632).

Specific CDKs operate in distinct phases of the cell cycle. CDK complexes with their respective type cyclin partners such as, complex of CDK2 and cyclin A is responsible for the cell’s progression from G1 phase to S phase (Sherr, C. J. Science 1996, 274, 1672). DNA synthesis (S phase) begins with the CDK mediated phosphorylation of Rb (retinoblastoma) protein. Phosphorylated Rb is released from its complex with E2F. The released E2F then promotes the transcription of numerous genes required for the cell to progress through S phase, including thymidylate synthase and dihydrofolate reductase which are required for cell progression (Hatakeyama, M. et. al, Cell Cycle Res. 1995, 1, 9; Zhang, H. S. et. al. Cell 1999, 97, 53). Majority of human cancers have abnormalities in some component of the Rb pathway because of hyper-activation of CDKs resulting from the over-expression of positive cofactors (cyclins/CDKs) or a decrease in negative factors (endogenous CDK inhibitors) or Rb gene mutations (Sausville, E. A. et. al, Pharmacol. Ther. 1999, 82, 285).

The CDK-9 is a member of the Cdc2-like family of kinases. Its cyclin partners are members of the family of cyclin T (T1, T2a and T2b) and cyclin K. The CDK-9/cyclin T complexes appear to be involved in regulating several physiological processes. CDK9/cyclin T1 belongs to the P-TEFb complex, and is responsible for the phosphorylation of carboxyl terminal domain of the RNA Polymerase II, thus promoting general elongation. CDK-9 has also been described as the kinase of the TAK complex, which is homologous to the P-TEFb complex and is involved in HIV replication. CDK9 also appears to be involved in the differentiation program of several cell types, such as muscle cells, monocytes and neurons, suggesting that it may have a function in controlling specific differentiative pathways. In addition, CDK-9 seems to have an anti-apoptotic function in monocytes, that may be related to its control over differentiation of monocytes. This suggests the involvement of CDK-9 in several physiological processes in the cell, the deregulation of which may be related to the genesis of transforming events that may in turn lead to the onset of cancer. In addition, since the complex CDK-9/cyclin T1 is able to bind to the HIV-1 product Tat, the study of the functions of CDK-9/cyclin T may be of interest in understanding the basal mechanisms that regulate HIV replication (Falco, G. D. and Giordano A. Cancer Biol. Therapy 2002, 1, 337).

Rohitukine belongs to a class of chromone alkaloids and it was isolated by chemists at Hoechst India Ltd. in the early 1990’s from Dysoxylum binectariferum Hook. which is phylogenetically related to the Ayurvedic plant, D. malabaricum Bedd., used for rheumatoid arthritis. Rohitukine was isolated as the constituent responsible for anti-inflammatory and immunomodulatory activity (Naik, R. G. et. al. Tetrahedron 1988, 44, 2081; U.S. Pat. No. 4,900,727, 1990). Medicinal chemistry efforts around this nature-derived flavone alkaloid led to discovery of two promising clinical candidates for treatment of cancer viz. flavopiridol of Sanofi-Aventis and P-276-00 of Piramal life sciences. Recently FDA has granted the orphan drug status to flavopiridol for treatment of chronic lymphocytic leukemia (CLL).

The molecular formula of rohitukine is C16H19NOand the structure has a molecular weight of 305.32 g/mol. The chemical structure of rohitukine (1) is shown below. The present invention reports new semi-synthetic analogs of rohitukine as promising inhibitors of cyclin-dependent kinases such as CDK-2 and CDK-9.

Figure US09932327-20180403-C00002

Synthesis of styryl analog 2-(2,6-dichlorostyryl)-5,7-dihydroxy-8-(3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (33)

This compound was synthesized using the procedure as described in example 4. Yellow solid; 1H NMR (DMSO-d6, 400 MHz): δ 7.68 (m, 2H), 7.61 (d, J=16 Hz, 1H), 7.49 (t, J=8 Hz, 1H), 7.14 (d, J=16 Hz, 1H), 6.41 (s, 1H), 5.85 (s, 1H), 4.53 (brs, 1H), 3.10-2.50 (m, 6H of piperidine), 2.65 (s, 3H), 1.62 (m, 1H); 13C NMR (DMSO-d6, 125 MHz): δ 179.68. 171.27, 159.20, 158.02, 154.03, 133.12, 131.49, 129.75, 128.35 (2C), 128.20, 127.90, 108.81, 106.79, 100.88, 100.52, 66.35, 59.82, 54.45, 43.15, 35.79, 22.01, 20.33, ESI-MS: m/z 462.01 [M+H]+; IR (CHCl3): νmax 3400, 2921, 1652, 1577, 1550, 1417, 1380, 1191, 1085 cm−1.

///////////IIIM-290, nda, india, phase 1, dcgi, CSIR, ROHITUKINE

[1]. Bharate SB, et al. Discovery and Preclinical Development of IIIM-290, an Orally Active Potent Cyclin-Dependent Kinase Inhibitor. J Med Chem. 2018 Feb 22;61(4):1664-1687.


Specific Stereoisomeric Conformations Determine the Drug Potency of Cladosporin Scaffold against Malarial Parasite




Specific Stereoisomeric Conformations Determine the Drug Potency of Cladosporin Scaffold against Malarial Parasite

Pronay Das†ab, Palak Babbar†c, Nipun Malhotra†c, Manmohan Sharmac , Goraknath R. Jachakab , Rajesh G. Gonnadebd, Dhanasekaran Shanmugambe, Karl Harlosf , Manickam Yogavelc , Amit Sharmac *, and D. Srinivasa Reddyab* †All three have contributed equally to this work.
aOrganic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India
b Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India
cMolecular Medicine Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India dCenter for Material Characterization, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India
e Biochemical Sciences Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India
fDivision of Structural Biology, Welcome Trust Centre for Human Genetics, The Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
J. Med. Chem., Just Accepted Manuscript
DOI: 10.1021/acs.jmedchem.8b00565
Publication Date (Web): May 21, 2018
Copyright © 2018 American Chemical Society
The dependence of drug potency on diastereomeric configurations is a key facet. Using a novel general divergent synthetic route for a three-chiral centre anti-malarial natural product cladosporin, we built its complete library of stereoisomers (cladologs) and assessed their inhibitory potential using parasite-, enzyme- and structure-based assays.
We show that potency is manifest via tetrahyropyran ring conformations that are housed in the ribose binding pocket of parasite lysyl tRNA synthetase (KRS). Strikingly, drug potency between top and worst enantiomers varied 500-fold, and structures of KRS-cladolog complexes reveal that alterations at C3 and C10 are detrimental to drug potency where changes at C3 are sensed by rotameric flipping of Glutamate332.
Given that scores of anti-malarial and anti-infective drugs contain chiral centers, this work provides a new foundation for focusing on inhibitor stereochemistry as a facet of anti-microbial drug development.
Cladosporin (12) displays exquisite selectivity for the parasite lysyl-tRNA synthetase over human enzyme. This species specific selectivity of cladosporin has been previously described through comprehensive sequence alignment, where the residues val329 and ser346 seem to be sterically crucial for accommodating the methyl moiety of THP ring10. The structural features of compound 12 clearly indicate the presence of three stereocenters, and therefore 2n (n=3) i.e., eight stereoisomers are possible (Fig.1). Till date, only one asymmetric total synthesis of cladosporin13 has been achieved which was followed by another report of formal syntheses14. Here, we have developed a general chemical synthesis route to synthetically access all the eight possible stereoisomers of compound 12.
cladosporin (compound 12) (0.052 g) as a white solid with a yield of 54 %. Melting point: 171-173 °C; [α]25 D = -15.75 (c = 0.6, EtOH); IR υmax(film): cm-1 3416, 3022, 1656, 1218; 1H NMR (400 MHz, CDCl3): δ 11.06 (s, 1H), 7.47 (br. s., 1H), 6.29 (s, 1H), 6.16 (s, 1H), 4.68 (t, J = 9.8 Hz, 1H), 4.12 (s, 1H), 4.01 (s, 1H), 2.89 – 2.75 (m, 2H), 2.00 – 1.94 (m, 1H), 1.87 – 1.81 (m, 1H), 1.70 – 1.63 (m, 4H), 1.35 (d, J = 6.1 Hz, 2H), 1.23 (d, J = 6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 169.9, 164.3, 163.1, 141.8, 106.7, 102.0, 101.5, 76.3, 68.0, 66.6, 39.3, 33.6, 30.9, 18.9, 18.1; HRMS calculated for C16H21O5 [M + H]+ 293.1384, observed 293.1379.


Dr. D. Srinivasa Reddy has been appointed as an editor of Bioorganic & Medicinl Chemistry Letters, Elsevier Publications. Congratulation Sir !

Click here for details.

The research interests of his group lie in issues related to application of oriented organic synthesis, in particular total synthesis of biologically active natural products, medicinal chemistry and crop protection. This team has been credited with having accomplished total synthesis of more than 25 natural products with impressive biological activities. “Some of our recent achievements include identification of potential leads, like antibiotic compound based on hunanamycin natural product for treating food infections, anti-diabetic molecule in collaboration with an industry partner and  anti-TB compound using a strategy called ‘re-purposing of a drug scaffold’,” said Reddy.

A total of two awardees out of four were from CSIR institutes. In addition to Reddy, Rajan Shankarnarayanan, CSIR – CCMB, Hyderabad (basic sciences), also was conferred with the award. Vikram Mathews, CMC, Vellore (medical research) and Prof Ashish Suri, AIIMS, New Delhi (clinical research), were the others to receive the awards.

With more than 80 scientific publications and 35 patents, Reddy is one of the most prominent scientists in the city and has already been honoured with the Shanti Swarup Bhatnagar prize in chemical sciences. Reddy is also a nominated member of the scientific body of Indian Pharmacopoeia, government of India and was  elected as a fellow of the Telangana and Maharashtra Academies of Sciences in addition to the National Academy of Sciences, India (NASI).


CSIR, INDIA-WO PATENT–synthesis of amprenavir and saquinavir



A process for synthesis of syn azido epoxide and its use as intermediate in the synthesis of amprenavir and saquinavir
Published as ———WO-2013105118
Council of Scientific & Industrial Research


Gadakh, Sunita, Khanderao; Rekula, Reddy, Santhosh; Sudalai, Arumugam
Publication date 18-JUL-2013

HIV protease inhibitor

Disclosed herein is a novel route of synthesis of syn azide epoxide of formu 5, which is used as a common intermdeiate for asymmetric synthesis of HIV protease inhibitors such as Amprenavir, Fosamprenavir, Saquinavir and formal synthesis of Darunavir and Palinavir obtained by Cobalt- catalyzed hydrolyti kinetic resolution of racemic anti-(2SR, 3SR) – 3 -azido – 4 -phenyl – 1, 2- epoxybutane (azido-epoxide

IN2012DE82 10-JAN-2012 [priority]
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