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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 GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 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, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, 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 30 year tenure till date Dec 2017, 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 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, 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 19 lakh plus views on New Drug Approvals Blog in 216 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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Pfizer, GSK form productivity pact with Singapore’s A*Star

Pfizer, GlaxoSmithKline and engineering giant Siemens have signed on as founding members of a new consortium set up by Singapore’s Agency for Science, Technology and Research (A*Star) to address challenges such as costs, regulatory compliance and processes to bring drugs from trials to markets.


The Agency for Science, Technology and Research (Abbreviation: A*STAR; Chinese: 新加坡科技研究局) is a statutory board under the Ministry of Trade and Industry of Singapore. The Agency was established in 1991 to foster scientific research and talent for a knowledge-based Singapore.

Established in 1991 as the former National Science and Technology Board (NSTB), A*STAR was established with the primary mission to raise the level of science and technology in Singapore.[1]




The current chairman of A*STAR is Mr. Lim Chuan Poh. He was formerly the Permanent Secretary (Education) and the Chief of Defence Force. Mr Lim took over the reins of A*STAR from Mr. Philip Yeo, who later became Chairman of SPRING Singapore, on 1 April 2007.[2]


The scientific leadership includes Tan Chorh Chuan, George Radda, Sydney Brenner, David Lane, Charles Zukoski and used to include Prof Low Teck Seng. Prof Low Teck Seng left A*Star on 19 July 2012 to join the National Research Foundation of the Prime Minister’s Office.


A*STAR Entities


The agency is made up of:


  • The Biomedical Research Council (BMRC) – Oversees public sector research activities in the biomedical sciences
  • The Science and Engineering Research Council (SERC) – Oversees public sector research activities in the physical sciences & engineering
  • The A*STAR Joint Council (A*JC) – Promotes and supports interdisciplinary collaborations between biomedical sciences, and physical sciences & engineering
  • The A*STAR Graduate Academy (A*GA) – Administers science scholarships and other manpower development programs
  • Exploit Technologies Pte Ltd (ETPL) – Manages the intellectual property created by research institutes in Singapore, and facilitates technology transfer to industry
  • The Corporate Group – Supports the rest of the organisation with finance, human resources, legal and other services


The agency oversees 14 biomedical sciences, and physical sciences and engineering research institutes, and six consortia & centre, which are located in Biopolis and Fusionopolis, as well as their immediate vicinity.


A*STAR supports Singapore’s key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, hospitals, research centres, and with other local and international partners.


Research Institutes & Units


Biomedical Research Council


The Biomedical Research Council (BMRC) oversees 7 research institutes and several other research units that focus on both basic as well as translational and clinical research to support the key industry clusters in Biomedical Sciences, pharmaceuticals, medical technology, biotechnology and healthcare services.


Having established a strong foundation in basic biomedical research capabilities, there is now an added focus on translating new knowledge and technologies created at the “benches” into new clinical applications for diagnosis and treatment that can one day be delivered at the “bedsides” of our hospitals and disease centres.


The research institutes and units under BMRC are:



The BMRC Research Institutes focus on building up core biomedical capabilities in the areas of bioprocessing; chemical synthesis; genomics and proteomics; molecular and cell biology; bioengineering and nanotechnology and computational biology. In addition, the Institute of Medical Biology (IMB) and Singapore Institute for Clinical Sciences (SICS) focus on translational and clinical research.


Science and Engineering Council


A*STAR’s Science and Engineering Research Council (SERC) promotes public sector research and development in the physical sciences & engineering.


SERC manages seven research institutes and several state-of-the art centres and facilities with core competencies in a wide range of fields including communications, data storage, materials, chemicals, computational sciences, microelectronics, advanced manufacturing and metrology to tackle global technological challenges and create future industries from its headquarters at Fusionopolis, Singapore’s iconic hub for science and technology research.


The research institutes and units under SERC are:



The seamless integration of the research institutes is key to addressing industry needs, which may span multiple disciplines. To this end, SERC’s broad range of capabilities are in a unique position to develop new technologies in areas such as automotives, aerospace, energy, electronic healthcare and medical technology, nanotechnology, photonics, sensors and sensor networks.


In July 2012, it was announced that A*STAR collaborates with Chinese language internet search provider Baidu to open a joint laboratory, called the Baidu-I2R Research Centre (BIRC), which aims to develop language processing technologies.[3]




Each year, the Agency gives out a number of scholarships and awards to young and aspiring scientists. These awards are meant to help Singapore achieve its goal of becoming a research hub by nurturing home-grown PhDs to serve both in the public sector and in industry. In 2008, a total of 101 scholarships were awarded to Bachelor of Science and PhD students who were to embark on their studies in overseas universities.[4] The administration of these awards are governed by the A*Star Graduate Academy, some of which are listed below:


  • National Science Scholarship (BS)
  • National Science Scholarship (PhD)
  • A*Star Graduate Scholarship
  • Singapore International Graduate Award (SINGA)
  • Singapore International Pre-Graduate Award (SIPGA)
  • A*Star Pre-Graduate Award
  • A*Star International Fellowship





PFIZER’S Palbociclib Granted Breakthrough Label by the Food and Drug Administration

1. Pyrido[2,3-d]pyrimidin-7(8H)-one, 6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(1-
2. 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2-
TRADEMARK None as yet
SPONSOR Pfizer Inc.
CAS#:  571190-30-2 (PD0332991);  827022-32-2 (PD0332991 HCl salt)  FOR STRUCTURE AND DETAILS

Palbociclib, also known as PD0332991, is an orally available pyridopyrimidine-derived cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. PD-0332991 selectively inhibits cyclin-dependent kinases (particularly Cdk4/cyclin D1 kinase), which may inhibit retinoblastoma (Rb) protein phosphorylation; inhibition of Rb phosphorylation prevents Rb-positive tumor cells from entering the S phase of the cell cycle (arrest in the G1 phase), resulting in suppression of DNA replication and decreased tumor cell proliferation. PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC50 = 0.011 μmol/L) and Cdk6 (IC50 =  0.016 μmol/L), having no activity against a panel of 36 additional protein kinases. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Date: April 10, 2013

Pfizer Inc. said that its experimental pill for advanced, often deadly breast cancer has been designated as a breakthrough therapy by the Food and Drug Administration.

The breakthrough designation, created under legislation enacted last summer to fund and improve operations of the FDA, is meant to speed up development and review of experimental treatments that are seen as big advances over existing therapies for serious diseases. Pfizer is working with the agency to determine exactly what research results it will need to apply for approval of the drug.

Palbociclib is being evaluated as an initial treatment for the biggest subgroup of postmenopausal women whose breast cancer is locally advanced or has spread elsewhere in the body. About 60% of women with such advanced breast cancer have tumors classified as ER+, or estrogen-receptor positive, but HER2-, or lacking an excess of the growth-promoting protein HER2.

Estrogen-receptor positive tumors have proteins inside and on the surface of their cells to which the estrogen hormone can attach and then fuel growth of cells. These tumors tend to grow slowly and can be fought with drugs that block estrogen’s effects.

Meanwhile, about 80% of breast cancer tumor cells are HER2 negative. That means that unlike HER2 positive tumors, they don’t produce too much of the HER2 protein, which makes tumors grow and spread more aggressively than in other breast cancer types.

New York-based Pfizer is currently running a late-stage study of palbociclib at multiple centers, comparing its effects when used in combination with letrozole with the effects of letrozole alone.

Letrozole, sold under the brand name Femara for about the past 15 years, is a pill that works by inhibiting aromatase. That’s an enzyme in the adrenal glands that makes estrogen.

According to Pfizer, palbociclib targets enzymes called cyclin dependent kinases 4 and 6. By inhibiting those enzymes, the drug has been shown in laboratory studies to block cell growth and suppress copying of the DNA of the cancer cells.

Pfizer, which has made research on cancer medicines a priority in recent years, also is testing palbociclib as a treatment for other cancers.

Highlight of recent study using PD-0332991

Phase I study of PD-0332991: Forty-one patients were enrolled. DLTs were observed in five patients (12%) overall; at the 75, 125, and 150 mg once daily dose levels. The MTD and recommended phase II dose of PD 0332991 was 125 mg once daily. Neutropenia was the only dose-limiting effect. After cycle 1, grade 3 neutropenia, anemia, and leukopenia occurred in five (12%), three (7%), and one (2%) patient(s), respectively. The most common non-hematologic adverse events included fatigue, nausea, and diarrhea. Thirty-seven patients were evaluable for tumor response; 10 (27%) had stable disease for ≥4 cycles of whom six derived prolonged benefit (≥10 cycles). PD 0332991 was slowly absorbed (median T(max), 5.5 hours), and slowly eliminated (mean half-life was 25.9 hours) with a large volume of distribution (mean, 2,793 L). The area under the concentration-time curve increased linearly with dose. Using an E(max) model, neutropenia was shown to be proportional to exposure. CONCLUSIONS:
PD 0332991 warrants phase II testing at 125 mg once daily, at which dose neutropenia was the sole significant toxicity. (Source: Clin Cancer Res; 18(2); 568-76.)

Phase I study of PD-0332991 in 3-week cycles (Schedule 2/1): Six patients had DLTs (18%; four receiving 200 mg QD; two receiving 225 mg QD); the MTD was 200 mg QD. Treatment-related, non-haematological adverse events occurred in 29 patients (88%) during cycle 1 and 27 patients (82%) thereafter. Adverse events were generally mild-moderate. Of 31 evaluable patients, one with testicular cancer achieved a partial response; nine had stable disease (≥10 cycles in three cases). PD 0332991 was slowly absorbed (mean T(max) 4.2 h) and eliminated (mean half-life 26.7 h). Volume of distribution was large (mean 3241 l) with dose-proportional exposure. Using a maximum effective concentration model, neutropenia was proportional to exposure. CONCLUSION: PD 0332991 was generally well tolerated, with DLTs related mainly to myelosuppression. The MTD, 200 mg QD, is recommended for phase II study. (source: Br J Cancer. 2011 Jun 7;104(12):1862-8)


1: Flaherty KT, Lorusso PM, Demichele A, Abramson VG, Courtney R, Randolph SS, Shaik MN, Wilner KD, O’Dwyer PJ, Schwartz GK. Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer. Clin Cancer Res. 2012 Jan 15;18(2):568-76. doi: 10.1158/1078-0432.CCR-11-0509. Epub 2011 Nov 16. PubMed PMID: 22090362.

2: Smith D, Tella M, Rahavendran SV, Shen Z. Quantitative analysis of PD 0332991 in mouse plasma using automated micro-sample processing and microbore liquid chromatography coupled with tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Oct 1;879(27):2860-5. doi: 10.1016/j.jchromb.2011.08.009. Epub 2011 Aug 16. PubMed PMID: 21889427.

3: Katsumi Y, Iehara T, Miyachi M, Yagyu S, Tsubai-Shimizu S, Kikuchi K, Tamura S, Kuwahara Y, Tsuchiya K, Kuroda H, Sugimoto T, Houghton PJ, Hosoi H. Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression. Biochem Biophys Res Commun. 2011 Sep 16;413(1):62-8. doi: 10.1016/j.bbrc.2011.08.047. Epub 2011 Aug 17. PubMed PMID: 21871868; PubMed Central PMCID: PMC3214763.

4: Schwartz GK, LoRusso PM, Dickson MA, Randolph SS, Shaik MN, Wilner KD, Courtney R, O’Dwyer PJ. Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1). Br J Cancer. 2011 Jun 7;104(12):1862-8. doi: 10.1038/bjc.2011.177. Epub 2011 May 24. PubMed PMID: 21610706; PubMed Central PMCID: PMC3111206.

5: Nguyen L, Zhong WZ, Painter CL, Zhang C, Rahavendran SV, Shen Z. Quantitative analysis of PD 0332991 in xenograft mouse tumor tissue by a 96-well supported liquid extraction format and liquid chromatography/mass spectrometry. J Pharm Biomed Anal. 2010 Nov 2;53(3):228-34. doi: 10.1016/j.jpba.2010.02.031. Epub 2010 Feb 26. PubMed PMID: 20236782.

6: Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, Los G, Slamon DJ. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77. doi: 10.1186/bcr2419. PubMed PMID: 19874578; PubMed Central PMCID: PMC2790859.

7: Menu E, Garcia J, Huang X, Di Liberto M, Toogood PL, Chen I, Vanderkerken K, Chen-Kiang S. A novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model. Cancer Res. 2008 Jul 15;68(14):5519-23. doi: 10.1158/0008-5472.CAN-07-6404. PubMed PMID: 18632601.

8: Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, Albassam M, Zheng X, Leopold WR, Pryer NK, Toogood PL. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38. PubMed PMID: 15542782.

Europe grants conditional OK to Pfizer’s Bosulif

Good News For Pfizer’s Orphan Drug Bosulif (Bosutinib) in Europe



mar 28,2013

Regulators in Europe have given a partial green light to Pfizer ‘s leukaemia drug Bosulif.

The European Commission has granted conditional marketing authorisation for Bosulif (bosutinib) for the treatment of adults with chronic, accelerated or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukaemia (CML). The drug can be given to patients previously treated with one or more tyrosine kinase inhibitors ie Novartis’ Gleevec (imatinib) and Tasigna (nilotinib) or Bristol-Myers Squibb’s Sprycel (dasatinib).

The European Medicines Agency’s  (EMA) Committee for Medicinal Products for Human Use (CHMP) on January 17, 2013, adopts a positive opinion, recommending a conditional marketing authhorization for Pfizer’s orphan drug Bosulif (Bosutinib) for Chronic Leukemia (CML).  Bosutinib receives orphan designation from the European Commission (EC) on August 4, 2010, for CML.

Pfizer receives FDA approval on September 4, 2012, for orphan drug Bosulif (Bosutinib) for CML. Pfizer receives on February 24, 2009, FDA Orphan Drug Designation (ODD) for Bosutinib for CML.


Bosutinib (rINN/USAN; codenamed SKI-606, marketed under the trade name Bosulif) is atyrosine kinase inhibitor undergoing research for use in the treatment of cancer. [1] [2]Originally synthesized by Wyeth, it is being developed by Pfizer.

Some commercial stocks of bosutinib (from sources other than the Pfizer material used for clinical trials) have recently been found to have the incorrect chemical structure, calling the biological results obtained with them into doubt.[3]

Bosutinib received US FDA approval on September 5, 2012 for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+)chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy.[4][5][6]

  1. Puttini M, Coluccia AM, Boschelli F, Cleris L, Marchesi E, Donella-Deana A, Ahmed S, Redaelli S, Piazza R, Magistroni V, Andreoni F, Scapozza L, Formelli F, Gambacorti-Passerini C. In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells. Cancer Res. 2006 Dec 1;66(23):11314-22. Epub 2006 Nov 17.
  2. Vultur A, Buettner R, Kowolik C, et al. (May 2008). “SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells”.Mol. Cancer Ther. 7 (5): 1185–94. doi:10.1158/1535-7163.MCT-08-0126.PMC 2794837PMID 18483306.
  3.  Derek Lowe, In The Pipeline (blog), “Bosutinib: Don’t Believe the Label!”
  4. Cortes JE, Kantarjian HM, Brümmendorf TH, Kim DW, Turkina AG, Shen ZX, Pasquini R, Khoury HJ, Arkin S, Volkert A, Besson N, Abbas R, Wang J, Leip E, Gambacorti-Passerini C. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood. 2011 Oct 27;118(17):4567-76. Epub 2011 Aug 24.
  5. Cortes JE, Kim DW, Kantarjian HM, Brümmendorf TH, Dyagil I, Griskevicus L, Malhotra H, Powell C, Gogat K, Countouriotis AM, Gambacorti-Passerini C. Bosutinib Versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Results From the BELA Trial. J Clin Oncol. 2012 Sep 4. [Epub ahead of print]
  6. “Bosulif Approved for Previously Treated Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia”. 05 Sep 2012.

Pfizer receives FDA approval for the use of Prevnar 13® , Pneumococcal 13-valent Conjugate Vaccine

Prevnar 13

Publication date: 25 January 2013
Author: Pfizer

Pfizer Inc.  announced today that the U.S. Food and Drug Administration (FDA) has granted approval for the expansion of the company’s pneumococcal conjugate vaccine, Prevnar 13®* (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]), for use in older children and adolescents aged 6 years through 17 years for active immunization for the prevention of invasive disease caused by the 13 Streptococcus pneumoniae serotypes contained in the vaccine. For this age group, Prevnar 13 is administered as a one-time dose to patients who have never received Prevnar 13.1

“As a global leader in pneumococcal disease prevention, extending the impact of Prevnar 13 to older children and adolescents aged 6 through 17 years is a reflection of our dedication to improving public health worldwide,”said Susan Silbermann, president, vaccines, Pfizer. “We continue to work tirelessly to make this vaccine available to people at risk for invasive pneumococcal disease.”

The FDA approval followed submission and review of a Phase 3, open-label trial of Prevnar 13 in 592 older children and adolescents, including those with asthma.2 The study met all endpoints, demonstrating immunogenicity and establishing a safety profile in children aged 6 years through 17 years consistent with the safety profile established in previous trials in infants and young children.2

About Prevnar 13

Prevnar 13 was first introduced for use in infants and young children in December 2009 in Europe and in February 2010 in the U.S., and it is now approved for such use in nearly 120 countries worldwide. It is the most widely used pneumococcal conjugate vaccine in the world, and more than 500 million doses of Prevnar/Prevnar 13 have been distributed worldwide. Currently, Prevnar 13 is included as part of a national or regional immunization program in more than 60 countries, offering coverage against invasive pneumococcal disease to nearly 30 million children per year.3

Prevnar 13 is also approved for use in adults 50 years of age and older in more than 80 countries and it is the first and only pneumococcal vaccine to be granted World Health Organization prequalification in the adult population.3

About Pneumococcal Disease

Pneumococcal disease (PD) is a group of illnesses caused by the bacterium Streptococcus pneumoniae (S. pneumoniae), also known as pneumococcus.4 PD is associated with significant morbidity and mortality.4 Invasive manifestations of the disease include bacteremia (bacteria in the blood) and meningitis (infection of the tissues surrounding the brain and spinal cord).4 Invasive pneumococcal disease can affect people of all ages, although older adults and young children are at heightened risk.4,5,6

us fda data

STN#: 125324

Proper Name: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)
Tradename: Prevnar 13
Manufacturer: Wyeth Pharmaceuticals, Inc, License #0003


  • Active immunization for the prevention of pneumonia and invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F in persons 50 years of age or older.
  • Active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, for use in children 6 weeks through 17 years of age.
  • Active immunization for the prevention of otitis media caused by Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F for use in children 6 weeks through 5 years of age.

Pfizer presents Phase 3 safety and immunogenicity data on Prevnar 13® in adults with HIV

Publication date: 4 March 2013
Author: Pfizer


Pfizer Inc. (NYSE:PFE) presented today the results from a Phase 3 study demonstrating the immunogenicity, tolerability and safety of Prevnar 13®(Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein])in adults infected with human immunodeficiency virus (HIV). The results were presented at the 20th Conference on Retroviruses and Opportunistic Infections (CROI) in Atlanta, Ga.


These data support planned regulatory submissions seeking to include data on HIV-infected immunocompromised adults in the Prevnar 13 label in the United States, the European Union, and other countries around the world.

NDA-US Marketing by Ranbaxy, Alembic has announced that it has received an NDA approval for extended release version of Pfizer’s anti depressant drug Pristiq, Desvenlafaxine Base


read at

5 march 2013

Alembic has announced that it has received an NDA approval for extended release version of  Pfizer’s anti depressant drug Pristiq. Pristiq sell approximately  $550m in the US. Alembic has outlicensed rights to  Ranbaxy for marketing in the US. The company will start marketing the product immediately.

Alembic will manufacture and supply the drug to Ranbaxy for marketing in the US. Vadodara-based pharma player, Alembic Pharmaceuticals Limited has received the approval from the US Food and Drug Administration (USFDA) for a bioequivalent version of Pristiq by Pfizer.

In a statement filed with the Bombay Stock Exchange (BSE) on Tuesday, Alembic informed that it has received USFDA approval for its new drug application (NDA), desvenlafaxine base extended release tablets.
The company is the sponsor and manufacturer of the NDA. Desvenlafaxine base extended release tablets is a prescription medicine and it is Alimbic’s first 505 (B) (2) filing. The product is indicated for the treatment of major depressive disorder.”The company has entered into an out-licensing arrangement with Ranbaxy Pharmaceuticals Inc, a wholly-owned subsidiary of Ranbaxy Laboratories Limited for exclusively marketing the product in the US market,” the statement said.

The product will be available in 50 mg and 100 mg disage strengths. The product will be launched immediately.
As per the industry data, the current market size for Pristiq is approximately US $ 538 million (approx. Rs 2900 crore).

Pfizer Gains China Approval of Kinase-Specific Lung Cancer Drug, Xalkori (crizotinib)

File:Crizotinib structure.svg

Xalkori, crizotinib,

Crizotinib; 877399-52-5; Xalkori; PF-2341066; PF-02341066; (R)-crizotinib; 877399-52-5

Molecular Formula: C21H22Cl2FN5O
Molecular Weight: 450.336683 g/mol

Crizotinib an inhibitor of receptor tyrosine kinase for the treatment of non-small cell lung cancer (NSCLC). Verification of the presence of ALK fusion gene is done by Abbott Molecular’s Vysis ALK Break Apart FISH Probe Kit. This verification is used to select for patients suitable for treatment. FDA approved in August 26, 2011.

Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS positive patients

Feb 25, 2013

Pfizer has been granted China approval for Xalkori (crizotinib), an innovative treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive. The ALK-positive variation, which comprises between 3% and 5% of all NSCLC tumors, must be proved by a biomarker test. Pfizer said China’s approval came just eleven months after it submitted a new drug application to the SFDA for Xalkori

Crizotinib (trade name Xalkori,[1] Pfizer), is an anti-cancer drug acting as an ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) inhibitor, approved for treatment of some non-small cell lung carcinoma (NSCLC) in the US and some other countries, and undergoing clinical trials testing its safety and efficacy in anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumors in both adults and children.[2]

  1. FDA approves Xalkori with companion diagnostic for a type of late-stage lung cancer. U.S. Food and Drug Administration.
  2. NCT00932451 An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene

Crizotinib the core structure is a substituted pyridine, the 3 – position of the ether as a chiral center adjacent, so with Mitsunobu reaction to complete, as is a typical Mitsunobu SN2 reaction, the reaction chiral center occurs in reverse, so easy to control, no racemization occurs. Pyridine substituted at position 5 by Suzuki reaction constructed.
Compound 1 The activation of the hydroxyl groups of methanesulfonyl chloride, and then with a 4 – iodopyrazole reaction 2 , 2 to 4 Suzuki reaction conversion can be used, but will generate a large quantity of the reaction product of their coupling, the first 2 converted to a Grignard reagent, and then with a boronic acid ester of 3 reaction 4 .



(R)-3-[l-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(l-piperidin-4-yl-lH-py- razol-4-yl)-pyridin-2-ylamine, also known as Crizotinib, is represented by the Formula (I):

Formula (I)

Crizotinib is a potent small-molecule inhibitor of c-Met/HGFR (hepatocyte growth factor receptor) kinase and ALK (anaplastic lymphoma kinase) activity. Enantiomerically pure compound of formula I was first disclosed in US Patent No. 7,858,643. Additionally, the racemate of compound of formula I was disclosed in U.S. patent application 2006/0128724, both of these references discloses similar methods for the synthesis of Compound of Formula I.

Conventionally, the compounds of formula I are prepared by reacting Bis(pinacolato)diboron with protected 5-bromo-3-[l-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine in the presence of Pd catalyst. The obtained product after deprotection is reacted with N- protected 4-(4-bromo-pyrazol-l-yl)-piperidine in the presence of Pd Catalyst. The obtained product is filtered through celite pad and purified by Column Chromatography. The final product of formula I was obtained by deprotection of the purified compound by using HCl/dioxane. US Patent No. 7,858,643 provides enantiomerically pure aminoheteroaryl compounds, particularly aminopyridines and aminopyrazines, having protein tyrosine kinase activity. More particularly, US 7,858,643 describes process for the preparation of 3-[(lR)-l-(2,6- dichloro-3-fluorophenyl)ethoxy]-5-(l-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine. The Scheme is summarized below in Scheme- 1 :


wherein, “Boc” means tert-butoxycarbonyl; and a) (Boc)2, DMF, Dimethylaminopyridine b) Pd(dppf)Cl2, KOAc, Dichloromethane; c) HC1, Dioxane, Dichloromethane; d) Pd(PPh3)2Cl2, Na2C03, DME/H20; e) 4M HCl/Dioxane, Dichloromethane

A similar process has been disclosed in the U.S. patent application 2006/0128724 for the preparation of Crizotinib. J. Jean Cui et. al. in J. Med. Chem. 2011, 54, 6342-6363, also provides a similar process for the preparation of Crizotinib and its derivatives.

However, above mentioned synthetic process requires stringent operational conditions such as filtration at several steps through celite pad. Also column chromatography is required at various steps which is not only tedious but also results in significant yield loss. Another disadvantage of above process involves extensive use of palladium catalysts, hence metal scavengers are required to remove palladium content from the desired product at various steps which makes this process inefficient for commercial scale.

Yet another disadvantage of above process is the cost of Bis(pinacolato)diboron. This reagent is used in excess in the reaction mixture resulting in considerable cost, especially during large-scale syntheses.

US Patent No. 7,825,137 also discloses a process for the preparation of Crizotinib where Boc protected 4-(4-iodo-pyrazol-l-yl)-piperidine is first reacted with Bis(pinacolato)diboron in the presence of Pd catalyst. The reaction mixture is filtered through a bed of celite and the obtained filtrate is concentrated and purified by silica gel chromatography to give to form tert-butyl-4-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazol-l-yl]piperidine-l- carboxylate. To this compound, 5-bromo-3-[l-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]- pyridin-2-ylamine is added in the presence of a Pd catalyst. The reaction mixture is stirred for 16h at 87°C. The reaction mixture is filtered through celite pad and the concentrated filtrate is purified on silica gel column to obtain (4-{6-amino-5-[(R)-l-(2,6-dichloro-3-fluoro- phenyl)-ethoxy]-pyri- din-3-yl}-pyrazol-l-yl)-piperidine-l-carboxylic acid tert-butyl ester of 95% purity. To the solution of resulting compound in dichloromethane 4N HCl/Dioxane is added and thereby getting the reaction suspension is filtered in Buchner funnel lined with filter paper. The obtained solid is dissolved in HPLC water and pH is adjusted to 10 with the addition of Na2C03 Compound is extracted using dichloroform and is purified on a silica gel column by eluting with CH2Cl2 MeOH/NEt3 system to obtain Crizotinib. The scheme is summarized below in scheme 2:

Formula (i) Formula (ii)

Formula (iii) Formula (ii) ula (iv)

Formula (v) Formula (I)


Preparation of Crizotinib:

To a stirred solution of Tert-butyl 4-(4-{ 6-amino-5-[(li?)-l-(2,6-dichloro-3- fluorophenyl)ethoxy]pyridin-3 -yl } – lH-pyrazol- 1 -yl)piperidine- 1 -carboxylate (material obtained in Example 3) (l.Og, 0.00181 moles) in dichloromethane (-13 ml) at 0°C was added 4.0 M dioxane HQ (6.7 ml, 0.0272 moles). Reaction mixture was stirred at room temperature for 4h. After the completion of reaction monitored by TLC, solid was filtered and washed with dichloromethane (10 ml). The obtained solid was dissolved in water (20 ml); aqueous layer was extracted with dichloromethane (10×2). The pH of aqueous layer was adjusted to 9-10 with Na2C03 and compound was extracted with dichloromethane (10 x 3), combined organic layers were washed with water (20 ml), evaporated under vacuum to get solid product. The solid was stirred with ether (10 ml), filtered off, washed well with ether, dried under vacuum to get Crizotinib.

Yield: 0.45g (55 %)

HPLC Purity: 99.35 %

1HNMR (400 MHz, CDC13) δ: 7.76 (d, J = 1.6 Hz, 1H), 7.56 (s, 1H), 7.49 (s, 1H), 7.30 (dd, J = 9.2 Hz), 7.0 (m, 1H), 6.86 (d, J = 1.6 Hz, 1H), 6.09 ( q, J= 6.8 Hz, 1H), 4.75 (brs, 1H), 4.19 (m, 1H), 3.25 (m, 2H), 2.76 (m, 2H), 2.16 (m, 2H), 1.92 (m, 2H), 1.85 (d, J= 6.8 Hz, 3H), 1.67 (brs, 1H)



A novel approach for the synthesis of Crizotinib (1) is described. In addition, new efficient procedures have been developed for the preparation of (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol (2) and tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (4), the key intermediates required for the synthesis of Crizotinib.

Graphical abstract

Full-size image (16 K)


4-(4-Iodo-1H-pyrazol-1-yl)piperidine is a key intermediate in the synthesis of Crizotinib. We report a robust three-step synthesis that has successfully delivered multi-kilogram quantities of the key intermediate. The process includes nucleophilic aromatic substitution of 4-chloropyridine with pyrazole, followed by hydrogenation of the pyridine moiety and subsequent iodination of the pyrazole which all required optimization to ensure successful scale-up.

Graphical abstract

Full-size image (6 K)


Org. Process Res. Dev., 2011, 15 (5), pp 1018–1026
DOI: 10.1021/op200131n
Abstract Image

A robust six-step process for the synthesis of crizotinib, a novel c-Met/ALK inhibitor currently in phase III clinical trials, has been developed and used to deliver over 100 kg of API. The process includes a Mitsunobu reaction, a chemoselective reduction of an arylnitro group, and a Suzuki coupling, all of which required optimization to ensure successful scale-up. Conducting the Mitsunobu reaction in toluene and then crystallizing the product from ethanol efficiently purged the reaction byproduct. A chemoselective arylnitro reduction and subsequent bromination reaction afforded the key intermediate 6. A highly selective Suzuki reaction between 6 and pinacol boronate 8, followed by Boc deprotection, completed the synthesis of crizotinib 1.

3-[(1R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine 1

crizotinib1 (20.7 kg, 80%) as a white solid.

Mp 192 °C;

1H NMR (400 MHz, CDCl3) δ: 7.78 (d, J = 1.8 Hz, 1H), 7.58 (s, 1H), 7.52 (s, 1H), 7.31 (dd, J = 9.0, 4.9 Hz, 1H), 7.06 (m, 1H), 6.89 (d, J = 1.7 Hz, 1H), 6.09 (q, 1H), 4.79 (br s, 2H), 4.21 (m, 1H), 3.26 (m, 2H), 2.78 (m, 2H), 2.17 (m, 2H), 1.90 (m, 2H), 1.87 (d, J = 6.7 Hz, 3H), 1.63 (br s, 1H).

13C NMR (100.6 MHz, CDCl3) δ: 157.5 (d, J = 250.7 Hz), 148.9, 139.8, 137.0, 135.7, 135.6, 129.9, 129.0 (d, J = 3.7 Hz), 122.4, 122.1 (d, J = 19.0 Hz), 119.9, 119.3, 116.7 (d, J = 23.3 Hz), 115.0, 72.4, 59.9, 45.7, 34.0, 18.9.

LC-MS: found m/z 450.0, 451.0, 452.0, 453.0, 454.0, 455.0.

Anal. Calcd for C21H22Cl2FN5O: C, 56.01; H, 4.92; N, 15.55. Found: C, 56.08; H, 4.94; N, 15.80.

Cui, J. J.; Botrous, I.; Shen, H.; Tran-Dube, M. B.; Nambu, M. D.; Kung, P.-P.; Funk, L. A.; Jia, L.; Meng, J. J.; Pairish, M. A.; McTigue, M.; Grodsky, N.; Ryan, K.; Alton, G.; Yamazaki, S.; Zou, H.; Christensen, J. G.; Mroczkowski, B.Abstracts of Papers; 235th ACS National Meeting, New Orleans, LA, United States, April 6–10, 2008.

Cui, J. J.; Funk, L. A.; Jia, L.; Kung, P.-P.; Meng, J. J.; Nambu, M. D.; Pairish, M. A.; Shen, H.; Tran-Dube, M. B. U.S. Pat. Appl. U. S. 2006/0046991 A1, 2006.
WO2010048131A1 * Oct 20, 2009 Apr 29, 2010 Vertex Pharmaceuticals Incorporated C-met protein kinase inhibitors
WO2011042389A2 * Oct 4, 2010 Apr 14, 2011 Bayer Cropscience Ag Phenylpyri(mi)dinylazoles
US7825137 Nov 23, 2006 Nov 2, 2010 Pfizer Inc. Method of treating abnormal cell growth
US7858643 Aug 26, 2005 Dec 28, 2010 Agouron Pharmaceuticals, Inc. Crizotinib, a c-Met protein kinase inhibitor anticancer agent; 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine is crizotinib
US20060128724 Aug 26, 2005 Jun 15, 2006 Agouron Pharmaceuticals, Inc. Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors
1 J. JEAN CUI J. MED. CHEM. vol. 54, 2011, pages 6342 – 6363
2 ORG. PROCESS RES. DEV. vol. 15, 2011, pages 1018 – 1026
3 * PIETER D. DE KONING ET AL: “Fit-for-Purpose Development of the Enabling Route to Crizotinib (PF-02341066)“, ORGANIC PROCESS RESEARCH & DEVELOPMENT, vol. 15, no. 5, 16 September 2011 (2011-09-16), pages 1018-1026, XP055078841, ISSN: 1083-6160, DOI: 10.1021/op200131n
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