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Isradipine
CAS Registry Number: 75695-93-1
CAS Name: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methylethyl ester
Additional Names: isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-5-methoxycarbonyl-2,6-dimethyl-3-pyridinecarboxylate; 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydro-3-isopropyloxycarbonylpyridine-5-carboxylic acid methyl ester; isrodipine
Manufacturers’ Codes: PN-200-110
Trademarks: Clivoten (Lifepharma); DynaCirc (Novartis); Esradin (Sigma-Tau); Lomir (Novartis); Prescal (Novartis)
Molecular Formula: C19H21N3O5
Molecular Weight: 371.39
Percent Composition: C 61.45%, H 5.70%, N 11.31%, O 21.54%
Properties: mp 168-170°.
Melting point: mp 168-170°
Derivative Type: S(+)-Form
Manufacturers’ Codes: PN-205-033
Properties: Crystals from ether + hexane, mp 142°. [a]D20 +6.7° (c = 1.5 in ethanol).
Melting point: mp 142°
Optical Rotation: [a]D20 +6.7° (c = 1.5 in ethanol)
Derivative Type: R(-)-Form
Manufacturers’ Codes: PN-205-034
Properties: Crystals from ether + hexane, mp 140°. [a]D20 -6.7° (c = 1.67 in ethanol).
Melting point: mp 140°
Optical Rotation: [a]D20 -6.7° (c = 1.67 in ethanol)
Keywords: Antianginal; Antihypertensive; Dihydropyridine Derivatives; Calcium Channel Blocker; Dihydropyridine Derivatives.

Isradipine (tradenames DynaCirc, Prescal) is a calcium channel blocker of the dihydropyridine class. It is usually prescribed for the treatment of high blood pressure in order to reduce the risk of stroke and heart attack. More recent research in animal models suggests that isradipine may have potential uses for treating Parkinson’s disease Chan et al. 2007.

Isradipine is given as either a 2.5mg or 5mg capsule. [1]

 

read more on dipine series………http://organicsynthesisinternational.blogspot.in/p/dipine-series.html

 Isradipine is a drug used to lower blood pressure but recently it was found by a team from Nortwestern University, that this molecule can also slow the progression of Parkinson’s disease, and restore the dopamine neurons (In animals tests). Isradipine is a calcium channel blocker of the 1,4-dihydropyridine class with a benzoxadiazole moiety in position 4.
The synthesis of the 1,4-dihydropyridine ring is quite classic, the first step consists in a Knoevenagel reaction of methyl acetoacetate on the benzoxadiazole 4-carboxaldehyde using piperidine and acetic acid as catalyst and diisopropylether as solvent in a 61% yield (this is the first time I see a Knoevenagel reaction in an ether!!!???? DCM, Toluene OK, but maybe I am wrong). The second step of this synthesis is the condensation of the acrylate obtained with the isopropyl aminocrotonate in ethanol to give the desire 1,4-dihydropyridine Isradipine in 67% yield after recrystallisation.
(WO/2005/005437) An improved Process for the Manufacture of Isradipine (Shasun Chemical & Drugs Limited)

Isradipine is 4-(4-Benzofi–razanyl)-l,4-d–hydro-2,6-dimethyl-3,5- pyiicϊ-nedicarboxylic acid med yl 1-methylethyl ester having die chemical structure of formula (I).

Figure imgf000002_0001

( I ) Isradipine is therapeutically indicated for treating cardiovascular diseases.

The cardiovascular diseases include angina, pectoris, hypertension and congestive heart failure. It is also used to treat high blood pressure. Isradipine was disclosed in the German specification DE 2949491 and US patent Nos. 4466972 and 4567271. DE 2949491 describes the general procedure to prepare 1,4-dihydropyridine derivatives. US 4466972, GBQ2103203A, LU 0088342A9, EP 0000150A1, EP 0000150B1, AU 0538515B2 and od er related patents describe the general mediod for d e preparation of Benzoxadiazoles and dieir derivatives of general formula (EL). These references in its entirety is hereby incorporated by reference into this application.

Figure imgf000003_0001

( II ) Where in Ri is -CH3 and -R2 is — CH(CH3)2 it refers to Isradipine of formula ( I ). When Ri and R2 are not identical the general procedures described in diese patent specifications produces a mixture of isomers of formula ( II ). These procedures for the preparation of Isradipine is characteristic of formation of the isomeric impurities, 1) 4-(4-Benzoi-urazanyl)-l,4-α^ydro-2,6-climedιyl-3,5- pyridinedicarboxylic acid di-methyl ester of formula ( III ) and 2) 4-(4- Benzofurazanyl)-l,4-α^ydro-2,6-d–methyl-3,5-pyrid–nedicarboxylic acid di-1- med ylethyl ester of formula ( IV) along with Isradipine. The US patent 4466972 describes the preparation of compounds of general formula (II) by refluxing 2, 1, 3-benzoxadiazole-4-carboxaldehyde, keto ester and concentrated ammonia or a β-amino ester in presence of ethanol, followed by evaporation and purification by chromatography.

H

Figure imgf000004_0001

( HI )H

Figure imgf000004_0002

( I V ) Tl ese symmetrical ester isomers ( III ) and ( IN ) are difficult to separate from the Isradipine and the separation is effected only by a chromatographic purifications. The drawback witii the procedures described in these patents is that it is very difficult to produce die product in commercial quantities as it involves d e purification of the product by chromatographic separations. A single step process for the preparation of Isradipine was described in CH 661270. This procedure involves first reacting 2,l,3-benzoxadiazole-4- carboxaldehyde with isopropyl acetoacetate in the presence of catalytic quantities of acetic acid and piperidine in refluxing toluene, and further reacting it widi mediyl-β-aminocrotonate. The Isradipine formed in d e reaction mixture was dien- separated by toluene distillation followed by cyclohexane treatment. The crude product obtained was dien crystallised from etiianol to get Isradipine. When we have repeated this process in our laboratory we got the Isradipine with substantially higher amount of symmetrical ester isomers ( III ) and ( IV ) are present in d e product. Removal of these symmetrical ester isomers is very difficult even after several repurifications from ethanol.

Figure imgf000006_0001

Stap 2

Figure imgf000006_0002
Example 4
Preparation of Isradipine using crude 2-acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester Dissolved the crude 2-acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester obtained in example – 1 (25 g, 0.10 mol) in absolute edianol (375 ml) and added in to the solution isopropyl-β-aminocrotonate (13.15 ml, 0.09 mol). Stirred the reaction mixture under nitrogen atmosphere at 25-28 °C for 7 hr. Removed sample from d e reaction mixture and analysed die sample by qualitative HPLC. Distilled ethanol from the reaction mixture- under vacuum at 50°C. Dissolved d e residue in ethyl acetate (235 ml) and washed twice widi water (90 ml). Dried the organic layer over sodium sulphate and distillation under vacuum at 50 °C. Dissolved the concentrate in ethanol (65 ml) at 70°C and slowly cooled to 5°C to get die product crystallised. Filtered the product and washed with pre cooled ethanol (25 ml). Recrystauised the product from ethanol (60 ml) and dried at 70°C under vacuum to obtain Isradipine (yield = 20 g, purity = 98.2% and Impurity III = 0.64%, Impurity IV = 0.51% by HPLQ
Example 5 Preparation of Isradipine using purified 2-acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester Dissolved 2-acetyl-3-benzo–urazan-4-yl-acrylic acid methyl ester (25 g, 0.10 mol) in absolute ethanol (375 ml) and added in to the solution isopropyl-β- aminocrotonate (13.15 ml, 0.09 mol). Stirred the reaction mixture under nitrogen atmosphere at 25-28 °C for 5 hr. Removed sample from the reaction mixture and analysed the sample by qualitative HPLC. Distilled ethanol from the reaction mixture under vacuum at 50°C. Dissolved the residue in ethyl acetate (235 ml) and washed twice wid w?ater (90 ml). Dried die organic layer over sodium sulphate and distillation under vacuum at 50 °C. Dissolved the concentrate in ethanol (65 ml) at 70°C and slowly cooled to 5°C to get the product crystallised. Filtered the product. and washed with pre cooled ethanol (25 ml). Recrystallised the product from edianol (60 ml) and dried at 70°C under vacuum to obtain 25 g Isradipine (yield = 67%, purity 99.5%, Impurity III = 0.20%, and Impurity IV = 0.12% by HPLC)
Example 6 Preparation of Isradipine using purified 2-acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester Dissolved the purified 2-acetyl-3-benzofurazan-4-yl-acrylic acid mediyl ester, obtained in example — 3 (25 g, 0.10 mol) in absolute ethanol (375 ml) and added in to the solution isopropyl-β-aminocrotonate (13.15 ml, 0.09 mol). Stirred the reaction mixture under nitrogen atmosphere at 25-28 °C for 5 hr. Removed sample from the reaction mixture and analysed the sample by qualitative HPLC. Distilled ethanol from die reaction mixture under vacuum at 50°C. Dissolved die residue in ethyl acetate (235 ml) and washed twice with water (90 ml). Dried the organic layer over sodium sulphate and distillation under vacuum at 50 °C. Dissolved the concentrate in ethanol (65 ml) at 70°C and slowly cooled to 5°C to get the product crystallised. Filtered the product and washed with pre cooled ethanol (25 ml) and dried at 70°C under vacuum to obtain 30g Isradipine (purity = 99.4%, Impurity III = 0.22%, and Impurity IV = 0.11% by HPLC). Throughout this application, various publications are referenced.

Side effects

Common side effects include: [2]

  • Dizziness
  • Warmth, redness, or tingly feeling under your skin
  • Headache
  • Weakness, tired feeling
  • Nausea, vomiting, diarrhea, upset stomach
  • Skin rash or itching

Serious side effects include: [2]

  • Lightheadedness or fainting
  • Shortness of breath, especially from minimal physical activity
  • Swelling in the hands and feet
  • Rapid and/or heavy heartbeat
  • Chest pain

If you experience one or more of these serious side effects, contact your health care provider immediately.

Significant drug interactions

There are other interactions beyond those listed below. Make sure to speak with a Pharmacist or Doctor if you have any concerns.

Three major interactions are listed below.

1. It is advised that those using Isradipine not take Anzemet (Dolasetron), as both agents can cause a dose-dependent PR intervaland QRS complex prolongation. [3]

2. Onmel/Sporanox (Itraconazole) exhibits a negative inotropic effect on the heart and thus could spur an additive effect when used concomitantly with Isradipine. Onmel/Sporanox also inhibits an important cytochrome liver enzyme (CYP 450 3A4) which is needed to metabolize Isradipine and other Calcium Channel Blockers. This will increase plasma levels of Isradipine and could cause an unintentional overdose of the medication. Caution is advised when administering both agents together. [4]

3. Zanaflex (Tizanidine) demonstrates anti-hypertensive effects and should be avoided in patients taking Isradipine due to the possibility of synergism between both medications. [5]

4. The anti-biotic Rifadin (Rifampin) lowered plasma concentrations of Isradipine to below detectable limits. [1]

5. Tagamet (Cimetidine) increased Isradipine mean peak plasma levels. A downward dose adjustment may be necessary with this particular instance of polypharmacy. [1]

6. Severe hypotension was reported with Duragesic (Fentanyl) anesthesia when it was combined with other Calcium Channel Blockers. Even though Isradipine, another Calcium Channel Blocker, has not been used in conjunction with Fentanyl anesthesia in any studies, caution is advised. [1]

Note: There was no significant interaction between Isradipine and Warfarin (Coumadin), Isradipine and Microzide Hydrochlorothiazide, Isradipine and Lanoxin (Digoxin), and Isradipine and Nitrostat (Nitroglycerin).

Overdose

Symptoms of an Isradipine overdose include: [1]

read more on dipine series………http://organicsynthesisinternational.blogspot.in/p/dipine-series.html

…………………

US 4466972

http://www.google.com.na/patents/US4466972

read more on dipine series………http://organicsynthesisinternational.blogspot.in/p/dipine-series.html

………………………………….

http://www.google.com.ar/patents/CN101768153B?cl=en

isradipine is a class Benzofurazan dihydropyridine class of compounds, the synthesis is more complex, especially in the purified material is particularly difficult.

US Patent US4466972 and PCT application W02005 / 00437 respectively disclose two synthetic isradipine

Methods. However, the product prepared by conventional methods contain a certain amount of a formula homologues impurity, the impurity is structured as follows:

 

Figure CN101768153BD00041

 wherein, R1, R2 simultaneously or separately as methyl, ethyl and isopropyl. The homologue of the impurities with isradipine extremely difficult to separate, resulting in ineffective purification isradipine.

 In addition, conventional processes for preparing key intermediates involved in 4-methyl benzofurazan. However, the preparation method of the key intermediates is still unsatisfactory. For example, the Chinese Patent 200 510 125 267 (Publication No. CN1847233A) in

Discloses an intermediate 4-methyl benzofurazan preparation methods, the preparation process is as follows:

 

Figure CN101768153BD00051

 It is clear that the above method steps long, dangerous operation, poor control, and cause a lot of pollution.

 Accordingly, there is an urgent need to develop new, efficient and simple isradipine important intermediates for preparing 4-methyl benzofurazan method.

 

[0019]

Figure CN101768153BD00052

[0020] (b) in an inert solvent, such that 4-methyl benzofurazan oxide reduction to form 4-methyl benzofurazan, i.e. a compound of formula 3;

[0021]

Figure CN101768153BD00053

[0028]

Figure CN101768153BD00061

[0029] to form isradipine.

Figure CN101768153BD00081

 

Example 7 β – amino crotonic acid isopropyl ester (Compound 8)

 The isopropyl acetoacetate (72.0g, 0 5mol.), Ammonium acetate (57. 8g, 0 75mol.) And tert-butanol / ethanol (1: 1,600ml) were mixed in IOOOml flask, 300 mesh sieve (50g), heated to reflux, TLC plate monitor. After the reaction is substantially completed, cooled to room temperature, filtered and the filtrate was concentrated until no liquid was distilled off, the residual liquid was distilled under reduced pressure, to collect 110-120 ° C fraction (degree of vacuum of 0. IMPa) to give compound 8 (66. Og). Y = 92. 4%.

 1H-WR (CDCl3):…… 5 02-4 95 (1H, m), 4 48 (1H, s), 1 88 (3H, d), 1 23-1 21 (6H , d)

 Example 8 isradipine (Isradipine)

 In the protection teams, three-necked flask Compound 6 (3.0g, 20mmol), i3- amino crotonic acid isopropyl ester (Compound 8) (2. 7g, 16. 6mmol), methyl acetoacetate (3. 50g, 30mol), Ac2O (2. 05g, 20mmol), conc. H2SO4 (0. 4g, 4mmol) and tert-butanol / ethanol (1: 1,65ml) mixing the liquid phase monitoring, when the remainder is less than 3 Compound 6 When the 7% to terminate the reaction. The reaction was concentrated, the residue was dissolved CH2Cl2 (55ml), washed with water (45ml X Magic, dried, concentrated, drain pump, to give 6. 7g end yellow foam-like solid. Ethanol QOml) dissolved by heating, stirring crystallization (overnight) to give a pale yellow powder isradipine (4. 3g) (HPLC purity> 99.8%, impurity content homologues thereof are less than 0.1), yield 66.8%.

 1H-WR (CDCl3):…… 7 62-7 60 (lH, m), 7 31-7 26 (2H, m), 5 46 (lH, s), 4 92-4 . 86 (1H, m), 3. 57 (3H, s), 2. 32-2. 30 (6H, m), 1. 21-1. 19 (3H, d), 0. 95-0. 94 (3H, d)

 Comparative Example 1

isradipine (Isradipine) prepared by the United States Patent US4466972:

 In the protection teams, three-necked flask Compound 6 (3.0g, 20mmol), i3- amino crotonic acid isopropyl ester (Compound 8) (2. 7g, 16. 6mmol), methyl acetoacetate (3. 50g, 30mol), Ac2O (2. 05g, 20mmol), conc. H2SO4 (0. 4g, 4mmol) and ethanol (65ml) were mixed and stirred, the liquid phase monitoring, when the compound 6 is less than 3.7% remaining, the reaction is stopped. The reaction was concentrated, the residue was dissolved CH2Cl2 (55ml), washed with water (45ml X Magic, dried, concentrated, drain pump, to give 6. 3g end yellow foam-like solid. Ethanol OOml) was dissolved by heating, stirring crystallization (overnight) to give a pale yellow powder isradipine (4. Ig) (HPLC purity: 99.0%, impurity content was homologues greater than 0.3%), a yield of 63.7%.

 Compared with Comparative Example 1 (homolog impurity content was greater than 0.3%), was the content of impurities isradipine homologs prepared in Example 1-8 is less than 0.1% by the embodiment of the present invention.

 The 10 cases of isradipine

 Example 8 was repeated, except that, with t-butanol / ethanol (1: 2,70ml) or t-butanol / ethanol O: 1, 70ml) replaces t-butanol / ethanol (1: 1,65ml) 0

The results showed that isradipine yield of about 62%, the test substance impurity content of less than 0.1% homologous.

Further reading and references

  1.  “”Isradipine: Brands, Medical Use, Clinical Data””.
  2.  “Isradipine Side Effects”.
  3. “”Isradipine and Anzemet Drug Interactions””.
  4. “”Isradipine and Onmel Drug Interactions””.
  5.  “”Isradipine and Zanaflex Drug Interactions””.
  • Hattori T, Wang P (2006). “Calcium antagonist isradipine-induced calcium influx through nonselective cation channels in human gingival fibroblasts.”. Eur J Med Res 11 (3): 93–6. PMID 16751108.
  • Ganz M, Mokabberi R, Sica D (2005). “Comparison of blood pressure control with amlodipine and controlled-release isradipine: an open-label, drug substitution study.”. J Clin Hypertens (Greenwich) 7 (4 Suppl 1): 27–31. doi:10.1111/j.1524-6175.2005.04450.x. PMID 15858400.
  • Johnson B, Roache J, Ait-Daoud N, Wallace C, Wells L, Dawes M, Wang Y (2005). “Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine’s subjective and reinforcing effects.”. Int J Neuropsychopharmacol 8 (2): 203–13. doi:10.1017/S1461145704005036. PMID 15850499.
  • Fletcher H, Roberts G, Mullings A, Forrester T (1999). “An open trial comparing isradipine with hydralazine and methyl dopa in the treatment of patients with severe pre-eclampsia.”. J Obstet Gynaecol 19 (3): 235–8. doi:10.1080/01443619964977. PMID 15512286.
  • Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ (2007). “‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease.”.Nature 447 (3): 1081–1086. doi:10.1038/nature05865. PMID 17558391.

read more on dipine series………http://organicsynthesisinternational.blogspot.in/p/dipine-series.html

External links

…………

CN1847233A21 Nov 200518 Oct 2006圣玛精细化工有限责任公司Method for preparing 4-formoxylbenzofuran

US446697219 Mar 198221 Aug 1984Sandoz Ltd.Hypotensive, antiischemic, antispasmodic agents

WO2005005437A115 Jul 200420 Jan 2005Radhakrishnan Selvar MullaiyurAn improved process for the manufacture of isradipine.

References: Dihydropyridine calcium channel blocker. Prepn: P. Neumann, DE 2949491; idem, US 4466972 (1980, 1984 both to Sandoz). Prepn of enantiomers: A. Vogel, DE 3320616 (1983 to Sandoz), C.A. 101, 7162s (1984). Comparative study of in vitro effects on human and canine cerebral arteries: E. Müller-Schweinitzer, P. Neumann, J. Cereb. Blood Flow Metab.3, 354 (1983). Effect on a-adrenoceptor mediated vasoconstriction in rats: K. Jie et al., Arch. Int. Pharmacodyn. 278, 72 (1985). Pharmacokinetics: F. L. S. Tee, J. M. Jaffe, Eur. J. Clin. Pharmacol. 32, 361 (1987). Clinical evaluation in angina and coronary artery disease: C. E. Handler, E. Sowton, ibid. 27, 415 (1984); in hypertension: E. B. Nelson et al., Clin. Pharmacol. Ther. 40, 694 (1986). Comparison of hemodynamic effects of enantiomers: R. P. Hof et al., J. Cardiovasc. Pharmacol. 8, 221 (1986). Series of articles on pharmacology and clinical use: Am. J. Med. 86, 1-146 (1989).

 

read more on dipine series………http://organicsynthesisinternational.blogspot.in/p/dipine-series.html

Isradipine
Isradipine.png
Systematic (IUPAC) name
3-methyl 5-propan-2-yl 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
Clinical data
Trade names DynaCirc
AHFS/Drugs.com monograph
MedlinePlus a693048
  • C
Legal status
Routes Oral
Pharmacokinetic data
Bioavailability 15-24%
Protein binding 95%
Metabolism 100% Hepatic
Half-life 8 hours
Excretion 70% Renal, 30% Fecal
Identifiers
CAS number 75695-93-1 Yes
ATC code C08CA03
PubChem CID 3784
DrugBank DB00270
ChemSpider 3652 Yes
UNII YO1UK1S598 Yes
KEGG D00349 Yes
ChEMBL CHEMBL1648 Yes
Chemical data
Formula C19H21N3O5 
Molecular mass 371.387 g/mol

…….

Alleppey kerala INDIA…..Alappuzha

Alappuzha – Wikipedia, the free encyclopedia

en.wikipedia.org/wiki/Alappuzha

pronunciation (help·info)), also known as Alleppey, is the administrative headquarters of Alappuzha District of Kerala state of southern India. Alappuzha is the …

 
Map of alleppey.
 
 
 
 
 
 
 
 
 
 
 
 
 Table in restaurant after eating fish, Alleppey, Kerala, India, South Asia,
 
 
 
 
 
 
 PAGODA RESORTS ALLEPPEY KERALA INDIA
 
 

////////////

 

 


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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 GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 29 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 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 29 year tenure till date Aug 2016, Around 30 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, 25 Lakh plus views on dozen plus blogs, 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 13 lakh plus views on New Drug Approvals Blog in 212 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

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