WORLD RECORD VIEWS holder on THIS BLOG, ………live, by DR ANTHONY MELVIN CRASTO, Worldpeaceambassador, Worlddrugtracker, Helping millions, 100 million hits on google, pushing boundaries,2.5 lakh plus connections worldwide, 45 lakh plus VIEWS on this blog in 227 countries, 7 CONTINENTS ……A 90 % paralysed man in action for you, I am suffering from transverse mylitis and bound to a wheel chair, [THIS BLOG HOLDS WORLD RECORD VIEWS ]
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 amcrasto@gmail.com, 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......https://newdrugapprovals.wordpress.com/ , 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
A clinical trial has found that, compared with soybean oil, a limited duration of fish oil in the intravenous nutrition of children with intestinal failure is safe and effective in reversing the complication known as intestinal failure-associated liver disease. read all this at
The baldness drug propecia could help reduce the risk of prostate cancer with less side-effects than previously thought, according to a new study.
By Amir Khan, Everyday Health Staff Writer
Warding off prostate cancer may be as easy as growing your hair, according to new data published in the New England Journal of Medicine by researchers from the University of Texas Health Science Center at San Antonio. The researchers followed up on patients from one of their previous studies, and found that the baldness drug finasteride, also known as Propecia, reduced the risk of prostate cancer by more than a third, and resulted in less-severe side effects than previously thought.
“If you look at the number of prostate cancers that are diagnosed annually and multiply that by 30 percent, that’s the number of cancers we might be able to prevent each year,” Ian Thompson Jr., MD, study author and director of the Cancer Therapy & Research Center at the University of Texas, said in a statement. “That’s more than 71,000 men. That’s more than 175 jumbo jets full of men who won’t get cancer, who won’t face treatments with side effects like sexual dysfunction.”
Rasmusson GH, Reynolds GF, Steinberg NG, Walton E, Patel GF, Liang T, Cascieri MA, Cheung AH, Brooks JR, Berman C (November 1986). “Azasteroids: structure-activity relationships for inhibition of 5 alpha-reductase and of androgen receptor binding”. J. Med. Chem.29 (11): 2298–315. doi:10.1021/jm00161a028. PMID3783591.
^ Bhattacharya A, Dimichele LM, Dolling U, Douglas AW, Grabowski EJJ (1988). “Silylation-mediated oxidation of 4-aza-3-ketosteroids with DDQ proceeds via DDQ-substrate adducts”. Journal of the American Chemical Society110: 3318–9. doi:10.1021/ja00218a062.
CAMBRIDGE, Mass., Aug 14, 2013 (AP) — The Food and Drug Administration has granted an “orphan drug designation” to a potential hemophilia treatment from Alnylam Pharmaceuticals Inc.
Orphan drug status is awarded to drugs that could treat diseases that affect fewer than 200,000 people in the United States. It comes with some added marketing exclusivity.
The Cambridge, Mass., company said Wednesday that the agency gave the designation to a drug labeled ALN-AT3 for the treatment of hemophilia B. Alnylam has tested the drug in mice and plans to start studies involving humans early next year.
for the treatment of hemophilia B. Alnylam has tested the drug in mice and plans to start studies involving humans early next year.
The stem cell research division of the Tisch MS Research Center of New York announced that the U.S. Food and Drug Administration (FDA) approved autologous, mesenchymal stem cell-derived neural progenitor cells (MSC-NPs) as an Investigational New Drug (IND) for an open label, phase 1 clinical trial in the treatment of multiple sclerosis.
Johnson & Johnson’s multiple myeloma treatment Velcade has been cleared as a first-line therapy in the EU, boosting the number of patients eligible for treatment with the drug.
The European Commission gave the go-ahead for Velcade (bortezomib) as induction therapy in combination with dexamethasone and thalidomide in previously-untreated multiple myeloma patients who are eligible for high-dose chemotherapy and a stem cell transplant.
Bortezomib bound to the core particle in a yeast proteasome. The bortezomib molecule is in the center colored by atom type (boron = pink, carbon = cyan, nitrogen = blue, oxygen = red), surrounded by the local protein surface. The blue patch is catalyticthreonine residue whose activity is blocked by the presence of bortezomib.
Bortezomib (INN, originally codenamed PS-341; marketed as Velcade by Millennium Pharmaceuticals and Bortecad by Cadila Healthcare) is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsedmultiple myeloma and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease.
Bortezomib was originally synthesized in 1995 (MG-341) at a company called Myogenics, which soon changed its name to ProScript. After promising preclinical results, the drug (PS-341) was tested in a small Phase I clinical trial on patients with multiple myeloma cancer. ProScript ran out of money and was bought by Leukosite in May 1999. Leukosite in turn was bought byMillennium Pharmaceuticals in October 1999. At this point in time, the project had low priority amongst other projects at the company. This changed significantly when one of the first volunteers to receive the drug in the clinical trial achieved a complete response and were still alive four years later. At the time this was a remarkable result. Later clinical experimentation indicates the possibility of a complete response in 15% of patients in a similar condition, when treated with bortezomib.
In May 2003, seven years after the initial synthesis, bortezomib (Velcade) was approved in the United States by the Food and Drug Administration (FDA) for use in multiple myeloma, based on the results from the SUMMIT Phase II trial.
Another commercially available bortezomib product – Bortenat (Natco Pharma, India), reportedly contains substantially more active entity than declared, potentially and even more resulting in increase toxicity. Moreover, Bortenat has some other chemical and formulation deviations from the registered ethic product Velcade (Millennium Pharmaceuticals and Janssen-Cilag), with unclear clinical impact
Cdiffense trial to evaluate vaccine against a leading cause of life-threatening, healthcare-associated infections worldwide
SWIFTWATER, Pa., Aug. 5, 2013 /PRNewswire/ — Sanofi Pasteur, the vaccines division of Sanofi (EURONEXT: SAN and NYSE: SNY), announced today the initiation of its Phase III clinical program called Cdiffense to evaluate the safety, immunogenicity and efficacy of an investigational vaccine for the prevention of primary symptomatic Clostridium difficile infection (CDI). Clostridium difficile (C. diff) is a potentially life-threatening, spore-forming bacterium that causes intestinal disease. The risk of C. diff increases with age, antibiotic treatment and time spent in hospitals or nursing homes, where multiple cases can lead to outbreaks. The investigational vaccine is designed to help protect at-risk individuals from C. diff, which is emerging as a leading cause of life-threatening, healthcare-associated infections (HAIs)worldwide, read all at…………….
UK chemists have used a combination of flow chemistry methods with solid-supported scavengers and reagents to synthesise the active pharmaceutical ingredient, imatinib, of the anticancer drug Gleevec. The method avoids the need for any manual handling of intermediates and allows the drug to be synthesised in high purity in less than a day.
Gleevec, developed by Novartis, is a tyrosine kinase inhibitor used for the treatment of chronic myeloid leukaemia and gastrointestinal stromal tumours.
The anti-cancer drug Gleevec® is far more effective against a drug-resistant strain of cancer when the drug wraps the target with a molecular bandage that seals out water from a critical area. This image shows the bandage (black box) on the modified version of the drug, WBZ-7. (Credit: Image courtesy of Rice University)
A new study in Cancer Research finds that the anti-cancer drug Gleevec® is far more effective against a drug-resistant strain of cancer when the drug wraps the target with a molecular bandage that seals out water from a critical area.
Currently, no definitive proof shows the use of donepezil or other similar agents alters the course or progression of Alzheimer’s disease (AD). However, 6 to 12-month controlled studies have shown modest benefits in cognition and/or behavior.Pilot studies have reported donepezil therapy may potentially have effects on markers of disease progression, such as hippocampal volume. Therefore, many neurologists, psychiatrists, and primary-care physicians use donepezil in patients with Alzheimer’s disease. In 2005, the UK National Institute for Clinical Excellence (NICE) withdrew its recommendation for use of the drug for mild-to-moderate AD, on the basis of no significant improvement in functional outcome, quality of life, or behavioral symptoms. However, NICE revised its guidelines to suggest donepezil be used in moderate-stage patients for whom the evidence is strongest.
While the drug is currently indicated for mild to moderate Alzheimer’s, evidence from two clinical trials also indicates it may be effective for moderate to severe disease. An example of this is a Karolinska Institute paper published in The Lancet in early 2006, which states donepezil improves cognitive function even in patients with severe AD symptoms. In Oct. 2006 the U.S. Food and Drug Administration also approved Aricept for treatment of severe dementia.
Research leading to the development of donepezil began in 1983 at Eisai, and the first Phase I clinical trial took place in 1989. In 1996, Eisai received approval from the United States Food and Drug Administration (USFDA) for donepezil under the brand Aricept, which it co-marketed with Pfizer. As of 2011, Aricept was the world’s best-selling Alzheimer’s disease treatment. The first generic donepezil became available in November 2010 with the USFDA approval of a formulation prepared by Ranbaxy Labs. In April 2011 a second generic formulation, from Wockhardt, received tentative USFDA marketing approval
标题:
Cyclic amine cpd., its use and pharmaceutical compsns. comprising it
AU 8818216; EP 0296560; EP 0673927; EP 0742207; JP 1989079151; JP 1998067739; US 4895841; US 5100901
合成路线图解说明:The condensation of 5,6-dimethoxy-1-indanone (I) with 1-benzylpiperidine-4-carboxaldehyde (II) by means of butyllithium and diisopropylamine in THF gives 1-benzyl-4-(5,6-dimethoxy-1-oxoindan-2-ylidenemethyl)piperidine (III), which is reduced with H2 over Pd/C in THF and treated with HCl in dichloromethane – ethyl acetate.
标题:
Synthesis of 1-benzyl-4-[(5,6-dimethoxy[2-14C]-1-indanon)-2-yl]methylpiperidine hydrochloride (E-2020-14C)
作者:
Sugimoto, H.; Mishima, M.; Iimura, Y.
来源:
J Label Compd Radiopharm 1989,27(7),835-9
合成路线图解说明:The condensation of 5,6-dimethoxy-1-indanone (I) with 1-benzylpiperidine-4-carboxaldehyde (II) by means of butyllithium and diisopropylamine in THF gives 1-benzyl-4-(5,6-dimethoxy-1-oxoindan-2-ylidenemethyl)piperidine (III), which is reduced with H2 over Pd/C in THF and treated with HCl in dichloromethane – ethyl acetate.
作者:
Casta馿r, J.; Prous, J.
来源:
Drugs Fut 1991,16(1),16
合成路线图解说明:The condensation of 5,6-dimethoxy-1-indanone (I) with 1-benzylpiperidine-4-carboxaldehyde (II) by means of butyllithium and diisopropylamine in THF gives 1-benzyl-4-(5,6-dimethoxy-1-oxoindan-2-ylidenemethyl)piperidine (III), which is reduced with H2 over Pd/C in THF and treated with HCl in dichloromethane – ethyl acetate.
标题:
Synthesis of 1-benzyl-4-[(5,[C-11]6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine: A promising ligand for visualisation of acetylcholine esterase by PET
作者:
Santens, P.; DeReuck, J.; Dierckx, R.A.; Siegers, G.; Vermeirsch, H.; De Vos, F.
来源:
J Label Compd Radiopharm 2000,43(6),595
合成路线图解说明:11C-Labeled donepezil was prepared by methylation of 2-(1-benzylpiperidin-4-ylmethyl)-6-hydroxy-5-methoxyindan-1-one (I) with 11CH3I by means of tetrabutylammonium hydroxide in DMF.
Donepezil hydrochloride is a useful memory enhancer introduced by the Japanese pharmaceutical company Eisai. Its preparation was described in patent no. EP 296560. In this patent Donepezil was produced by reaction of 5,6-dimethoxy-1- indanone with 1 -benzyl-4-formylpiperidine in the presence of a strong base, such as lithium diisopropylamide followed by reduction of the double bond. According to this method, Donepezil was obtained (Scheme 1).Patent application WO 99/36405 describes another process for the synthesis of Donepezil. According to this patent, 2-alkoxycarbonyl-1-indanones are reacted with (4-pyridinyl) methyl halide moiety followed by hydrolysis and decarboxylation to give the 2-(4-pyridinyl)methyl-1-indanone derivative. This is followed by reaction with benzyl halides to obtain the corresponding quaternary ammonium salt, and followed by hydrogenation of the pyridine ring to obtain Donepezil (Scheme 2).Patent application WO 97/22584 describes the preparation of Donepezil by reaction of pyridine-4-carboxyaldehyde with malonic acid to give 3-(pyridin-4-yl)-2- propenoic acid, followed by hydrogenation of the double bond to give 3-(piperidin-4-yl)-2-propionic acid. Reaction of this intermediate with methyl chloroformate afforded 3-[N-(methyloxycarbonyl) piperidin-4-yl]propionic acid. This was followed by reaction with oxalyl chloride to give methyl 4-(2-chlorocarbonylethyl)piperidin-1-carboxylate. Reaction with 1,2-dimethoxybenzene in the presence of aluminum chloride afforded methyl 4-[3-(3,4-dimethoxyphenyl)-3-oxopropyl]piperidin-1 -carboxylate. Reaction with tetramethyldiaminomethane afforded 4-[2-(3,4-dimethoxybenzoyl)allyl] piperidin-1-carboxylate. Reaction with sulfuric acid afforded methyl 4-(5,6-dimethoxy-1-oxoindan-2-yl)methylpiperidin-1- carboxylate. This was followed by treatment with base to give 5,6-dimethoxy-2-(piperidin-4-ylmethyl) indan-1-one, then reaction with benzyl bromide afforded Donepezil (Scheme 3).
Patent application EP 711756 describes the preparation of Donepezil by reaction of 5,6-dimethoxy-1- indanone with pyridin-4-aldehyde to give 5,6-dimethoxy-2-(pyridin-4-yl)methylene indan-1-one. Reaction with benzyl bromide afforded 1-benzyl-4-(5,6-dimethoxyindan-1-on-2-ylidene)methylpyridinium bromide. Hydrogenation in the presence of platinum oxide afforded Donepezil (Scheme 4).
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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