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ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

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

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Avanir said the FDA agreed to a faster development process for its experimental drug AVP-786 and will allow the company to use some data from studies of Nuedexta in its applications for AVP-786


6/may/2013

Avanir Pharmaceuticals Inc. announced that the Food and Drug Administration will allow it to speed research on a newer version of its drug Nuedexta.

Avanir said the FDA agreed to a faster development process for its experimental drug AVP-786 and will allow the company to use some data from studies of Nuedexta in its applications for AVP-786.

Avanir plans to start human clinical trials of the drug after it completes some limited preclinical testing. The company said the FDA’s decision could reduce the cost of developing the drug and allow it to win marketing approval sooner.

Nuedexta is a treatment for pseudobulbar affect, a condition that involves involuntary emotional outbursts like laughing or crying. It is associated with brain disease or injury. Net revenue from the drug more than doubled to $31.4 million over the first six months of the company’s current fiscal year. That was almost all of the Aliso Viejo, Calif., company’s revenue.

Nuedexta was approved in February 2011. The drug combines two ingredients: dextromethorphan, a common ingredient in cough and cold medicines that can suppress coughing, and quinidine, which is used to treat abnormal heart rhythms.

Avanir is also studying Nuedexta as a treatment for diabetic nerve pain, agitation in patients with Alzheimer’s disease, central nerve pain in multiple sclerosis, and levodopa-induced dyskinesia in Parkinson’s disease. Dyskinesias are involuntary movements tied to most treatments used to manage Parkinson’s.

Canaccord Genuity analyst Ritu Baral said Avanir considers AVP-786 to be a safer version of Nuedexta because it contains less quinidine. The drug also has stronger patent protection and is patent protected until 2030, a few years longer than Nuedexta.

In a telephone interview, Baral said the FDA’s decision could speed approval of AVP-786 by two to four years. She said Avanir may start late-stage testing of the drug in the second half of 2014 depending on the results of current studies of Nuedexta.

OPRD PAPER-An Improved Manufacturing Process for the Antimalaria Drug artemether


Abstract Image

Novartis Pharma AG, Chemical and Analytical Development and Chemical Operations, CH-4002 Basel, Switzerland.
Org. Process Res. Dev., 2007, 11 (3), pp 336–340
DOI: 10.1021/op0602425
Artemisinin and its derivatives, such as artemether, are highly sensitive compounds, which require careful optimized production processes for their manufacture. Due to robustness issues, the manufacturing procedure of the reduction of artemisinin with potassium borohydride to dihydroartemisinin was reinvestigated. The most important factor for obtaining optimal yields is to ensure low levels of contamination of potassium hydroxide in potassium borohydride. Application of a lower reaction temperature, fast addition rate of potassium borohydride, and careful control of the pH during the quench with acid are further important parameters in guaranteeing a robust process. In the redesign of the conversion of dihydroartemisinin to artemether, the yield was increased, and dichloromethane was replaced by the ecologically friendlier methyl acetate. A robust manufacturing process forartemether is now at hand, allowing the production of this important medicine reliably and in good quality and yield.

OPRD PAPER-Streamlined Process for the Conversion of Artemisinin to Artemether


Abstract Image
Clinton Health Access Initiative, 383 Dorchester Avenue, Suite 400, Boston, Massachusetts 02127, United States
Org. Process Res. Dev., 2012, 16 (5), pp 764–768
DOI: 10.1021/op300037e
PAPER reports an improvement to the previously published manufacturing process for artemether, a key antimalarial drug, utilizing readily available reagents, easily controlled manufacturing conditions, and a greatly simplified workup and isolation. New analytical methods and in-process controls allow for optimization of yield through control of side product formation. A 70% overall yield from the two-step conversion of naturally or synthetically derived artemisinin to pure β-artemether is obtained. This corresponds to a usage factor of 1.35 kg of artemisinin needed to produce 1 kg of β-artemether, compared to the current industry average of 1.59 kg.
Org. Process Res. Dev.201216 (8), pp 1455–1455
Publication Date (Web): August 1, 2012 (Addition/Correction)
DOI: 10.1021/op300201z
Correction to A Streamlined Process for the Conversion of Artemisinin toArtemether … The structure for β-artemether is shown above, with the correct stereochemistry shown at the anomeric (8a) position. … Assignments are correct for the α- and β-anomers of artemether and dihydroartemisinin as discussed in the text; only the structure drawings are in error. …
ACTs (Artemisinin) is extracted from the plant Artemisia annua out sesquiterpene lactones, is specific for malaria. With its discoverer Tu Yo Yo in 2011 received the Lasker Award for Clinical Medicine (Lasker Award), and because a number of the Lasker Award winners also won the Nobel Prize, artemisinin and its discoverer Tu Yo Yo won the Chinese public and widespread media attention.
The total synthesis of artemisinin from the Isopulegol ((-)-Isopulegol) began [JACS, 1983, 624].Contrast extracted from plants, is not an economical total synthesis method, but activity was found in the total synthesis of analogues are better practical significance of a thing. In this type of terpene total synthesis of natural products stereochemical conformation analysis is also very interesting. Hu menthol with MOMCl protected hydroxy, and get a double borohydride alcohol 1. Hydroboration Addition of anti-Markovnikov rule, which is replaced by hydrogen atoms added to the side of Quito, and the boron atoms added to the less substituted side. As the front side of the double bond MOM large steric hindrance, from the double rear borane adduct, resulting product1 . Compound 1 with a benzyl group protecting the primary alcohol, HCl removal of MOM protecting, PCC oxidation of the secondary alcohol to the ketone 3 . 3 with the hydrogen generating pull enolates LDA 4 , because of steric hindrance than hydrogen methyl, the nucleophilic reaction occurs in the torus , the form compound 5 . Ketone 5 and lithium reagent 6 an addition reaction, if one equivalent of lithium reagent, the resulting product was a 1:1 8 and 9 , if the 10-fold excess of lithium reagent, the resulting product was 8:1 8 and 9 . Lithium reagent 6 as a nucleophile large volume, its addition of cyclohexanone from the equatorial position to attack (such as an intermediate state 7 as shown), so that the generated key in an upright position hydroxyl group. Equivalent of lithium reagent no stereoselectivity of the reaction, but when a large excess of lithium, when chiral ketone 5 lithium reagent of the racemic 6 kinetic resolution becomes possible. Intermediate state 7 in, R configuration of the lithium reagent to Ketones speed is faster than its enantiomer S configuration lithium reagent. So generate eight faster than 9 , and finally get 8 and 9 of the ratio of 8:1. Lithium reagent 6, TMS air resistance maximum (A-value = 2.5 kcal / mol), OMe second air resistance (A-value = 0.75 kcal / mol), so that when the attack is downward TMS, OMe and H is determined by the relative position of cyclohexanone 2,6 substituent to the size and conformation of the decision, and should also be considered in the attack Burgi-Dunitz angle, so that the stereochemistry of the product unpredictable. Compound 8after removal of the benzyl protecting the primary alcohol with excess oxidized to carboxyl groups PCC automatically generate a macrolide 10 . 10 of the vinyl silane with m -CPBA and TFA into one11 , and then generate the enol methyl desilication TBAF ethers 12 , 12 and singlet oxygen reacts13 directly after treatment with acid artemisinin.
ACTs (Artemisinin) drugs to treat malaria
ACTs (Artemisinin) drugs to treat malaria

ACTs (Artemisinin) drugs to treat malaria

ACTs (Artemisinin) drugs to treat malaria

Sanofi Updates Lantus Label in EU, ORIGIN Results on Lantus® Cardiovascular Safety Integrated Into European Union Product Label


Lantus® (insulin glargine)

June 5, 2013 –

Sanofi  announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for inclusion in the Lantus® (insulin glargine) product label of safety and efficacy data from the insulin glargine cardiovascular (CV) outcomes trial ORIGIN (Outcome Reduction with Initial Glargine INtervention). The revised label is evidence of Sanofi’s ongoing commitment to further assert the well-known safety and efficacy profile of insulin glargine, the most-studied basal insulin. The indication for the use of Lantus® remains unchanged.

Mechanism of Action
White3
Insulin glargine (lantus) mechanism of action.

LANTUS (insulin glargine rdna origin injection) consists of insulin glargine dissolved in a clear aqueous fluid. Each milliliter of LANTUS (insulin glargine rdna origin injection) contains 100 IU (3.6378 mg) insulin glargine.

LANTUS® is a sterile solution of insulin glargine for use as an injection. Insulin glargine is a recombinant human insulin analog that is a long-acting (up to 24-hour duration of action), parenteral blood-glucose-lowering agent.,  LANTUS (insulin glargine rdna origin injection) is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acidasparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Chemically, it is 21A– Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin and has the empirical formula C267H404N72O78Sand a molecular weight of 6063.

FDA Approves Revlimid (lenalidomide) for the Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma


Lenalidomide  (Revlimid)

EP 0925294; US 5635517; WO 9803502,Drugs Fut 2003, 28, 5, 425.Bioorg Med Chem Lett 1999, 9, 11, 1625

RS)-3-(4-amino-1-oxo 1,3-dihydro-2H-isoindol- 2-yl)piperidine-2,6-dione

Jun. 5, 2013– Celgene Corporation today announced the U.S. Food and Drug Administration (FDA) has approved the company’s supplemental new drug application (sNDA) for Revlimid (lenalidomide) for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.

http://www.drugs.com/newdrugs/fda-approves-revlimid-lenalidomide-patients-relapsed-refractory-mantle-cell-lymphoma-3806.html

Revlimid is used to treat a certain type of myelodysplastic syndrome (a group of conditions in which the bone marrow produces blood cells that are misshapen and does not produce enough healthy blood cells) caused by an abnormal chromosome. Revlimid is also used to treat anemia (a lack of red blood cells in the body) and along with dexamethasone for the treatment of multiple myeloma (a type of cancer of the bone marrow) who have received at least one prior therapy.

Lenalidomide  (Revlimid) is a derivative of thalidomide introduced in 2004.

It was initially intended as a treatment for multiple myeloma, for which thalidomide is an accepted therapeutic treatment. Lenalidomide has also shown efficacy in the class of hematological disorders known as myelodysplastic syndromes (MDS). Lenalidomide has significantly improved overall survival in myeloma (which generally carries a poor prognosis), although toxicity remains an issue for users.  It costs $163,381 per year for the average patient.

Use in USA

On June 29, 2006, lenalidomide received U.S. Food and Drug Administration (FDA) clearance for use in combination with dexamethasone in patients with multiple myeloma who have received at least one prior therapy.

As of 2011, the FDA has initiated an ongoing review of Revlimid. The review focuses on clinical trials which found that Revlimid caused an increased risk of developing new malignancies such as acute myelogenous leukemia (AML) and B-cell lymphoma.The FDA is currently advising all patients on Revlimid to continue their treatment

Use in the UK

On 23 April 2009, The National Institute for Health and Clinical Excellence (NICE) issued a Final Appraisal Determination (FAD) approving lenalidomide, in combination with dexamethasone, as an option to treat patients who suffer from multiple myeloma who have received two or more prior therapies in England and Wales.

Use in Australia -While lenalidomide is not approved for first-line treatment of multiple myeloma in Australia, in clinical trials of newly diagnosed multiple myeloma, a four-fold increase in the incidence of second primary malignancies has been observed in patients receiving lenalidomide (7.0%) compared to controls (1.8%). These included cases of acute myeloid leukaemia, myelodysplastic syndrome and solid tumours in patients receiving lenalidomide.

Management of Hepatitis C with Natural and Synthetic Medicine


 Management of Hepatitis C with Natural and Synthetic Medicine by Khan Usmanghani, Asif Iqbal , Department of Basic Clinical Sciences, Faculty of Eastern Medicine , HAMDARD UNIVERSITY, Karachi, Pakistan

during the 6 th International Conference of Infection Control December 19, 2006 Liaquat National Hospital, Karachi

http://www.slideshare.net/icsp/management-of-hepatitis-c-with-natural-and-synthetic-medicine

 

Viral hepatitis is defined as viral infection of hepatocytes that produces necrosis and inflammation of the liver. Viral Hepatitis is a parenchymal disease of liver. This disease is caused by (a) Hepatotropic viruses A, B, C (Non-A-Non B), D,E,F,G,H (b) Other viruses like Epstein-Barr, Cytomegalovirus, and Coxsackie virus etc. Hepatitis C virus (HCV), the major causative agent of non-A and non-B hepatitis, poses a serious worldwide health problem. about 170 million people, 3% of the world’s population, are infected with HCV High prevalence rates Southeast Asian countries WHO

DENGUE FEVER by Prof. D. S. Akram, Dr. Saba Ahmed


Outline of a human torso with arrows indicating the organs affected in the various stages of dengue fever

Dengue fever (DF) and Dengue hemorrhagic fever (DHF) rank high among infectious diseases and are considered to be most important of arthropod born viral diseases

MOSQUITO VECTOR DF is caused by mosquito of genus Aedes ,most important is A.aegypti which is a day biting mosquito, rests indoors and can breed in small collection of water. Rainy season increase risk of DF as it increases larval population ,also ambient temperature and humidity favor viral propagation

Chikungunya an update by Dr.T.V.Rao MD


The Aedes aegypti mosquito biting a person.

WHAT IS CHIKUNGUNYA• Manifest with Crippling Arthritic disease of sudden onset.• Name is derived from Swahili – Chikungunya meaning that which bends up• Virus isolated in 1953 from serum and Aedes mosquitoes and Culex spp

Chikungunya is a virus that is transmitted from human to human mainly by infected Aedes albopictus and Aedes aegypti mosquitoes (later referred to as Aedes mosquitoes) acting as the disease-carrying vector• Chikungunya causes sudden onset of high fever, severe joint pain, muscle pain and headache• As no vaccine or medication is currently available to prevent or cure the infection, control of Chikungunya involves vector control measures and encouraging people to avoid mosquito bites
http://www.slideshare.net/doctorrao/chikungunya-an-update

Ayurveda Cure of Malaria


Malaria is a worldwide problem. Ayurveda, the Indian system of medicine have answer to cure the Malaria and its complications.

http://www.slideshare.net/drdbbajpai/ayurveda-cure-of-malaria

Ayurveda Herbs : Medicinal uses of Turmeric


http://www.slideshare.net/drdbbajpai/ayurveda-herbs-medicinal-uses-of-turmeric?from_search=2

………………

Composition

Curcumin keto form

Curcumin enol form

Turmeric contains up to 5% essential oils and curcumin of about three percent by weight, a polyphenol. Curcumin is the active substance of turmeric and curcumin is known as C.I. 75300, or Natural Yellow 3. The systematic chemical name is (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione.

It can exist at least in two tautomeric forms, keto and enol. Curcumin is a pH indicator. In acidic solutions (pH <7.4) it turns yellow, whereas in basic (pH > 8.6) solutions it turns bright red.