DR ANTHONY MELVIN CRASTO,WorldDrugTracker, helping millions, A 90 % paralysed man in action for you, I am suffering from transverse mylitis and bound to a wheel chair, With death on the horizon, nothing will not stop me except God................DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 25Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK GENERICS at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution

Monday 27 April 2015

AZILSARTAN


 
AzilsartanMedoxomil Potassium
Glitter 

(5-methyl-2-oxo-l,3-dioxol-4-yl)methyl 2- ethoxy- 1 - { [2'-(5-oxo-4,5-dihydro- 1 ,2,4-oxadiazol-3-yl)biphenyl-4yl]methyl} - 1 H- benzimidazole-7-carboxylate monopotassium salt
AzilsartanMedoxomil Potassium is chemically named as (5-Methyl-2-oxo-1, 3-dioxol-4yl) methyl 2-ethoxy-1-{[2- (5-oxo-4, 5-dihydro-1, 2, 4-oxadiazol-3-yl) biphenyl-4-yl]methyl}- 1H-benzimidazole-7-carboxylatemonopotassium salt. Azilsartanmedoxomil is the prodrug of 2-ethoxy-1-([2'-(5-oxo4,5 – dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4- yl]methyl) 1H-benimidazole-7-carboxylic acid.It is a white crystalline powder insoluble in water, slightly soluble in solvents such as acetone, and acetonitrile, freely soluble in methanol, dimethylsulfoxide, and dimethylformamide, soluble in solvents such as acetic acid, and very slightly soluble in solvents tetrahydrofuran and 1-octanol.
The US Food and Drug Administration (FDA) has approved Edarbi tablet (AzilsartanMedoxomil Potassium) on February 25, 2011, to treat hypertension in adults. It is available in 80mg and 40 mg dosages, with the recommended dosage set at 80mg once in a day [1].
Angiotensin II hormone plays a vital role in activation of renin-angiotensinaldosterone systems well as in regulation of blood pressure, fluid-electrolyte balance, and also in pathophysiology of hypertension. Activation of type 1 angiotensin receptor which is a member of G protein coupled receptor efficiently controls the numerous effects of AII which are vasoconstriction, secretion of aldosterone and vasopressin and cellular proliferation. So blocking of AII receptor will also block receptor-1, and it will lead to termination of the whole course of action mentioned above;
so all blocker will be helpful in the management of cardiovascular and renal diseases as therapeutic agent.The active moiety of AMP is revealed by hydrolysis of the medoxomil ester and it converts into azilsartan which is an active angiotensin II receptor blocker and more effective in lowering blood pressure within 24 hours as compared to valsartan and olmesartan[2-5].There are several methods that are reported for preparation of azilsartan [6-15].
The presence of related substances in an active pharmaceutical ingredient (API) can have a significant impact on the quality and safety of the drug products. Therefore, it is necessary to study the impurity (related substance) profile of the API to be used in the manufacturing of the drug product. International Conference on Harmonization (ICH)guidelines recommends identifying and characterizing all related substancesthat are present at level less than 0.10% [16].


GlitterGlitterGlitterGlitter
2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid
AZILSARTAN
2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid
CAS No.:147403-03-0
Synonyms:
  • UNII-F9NUX55P23;
  • 1H-Benzimidazole-7-carboxylic acid,1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]methyl]-2-ethoxy;
  • TAK 536;
  • azilsartan acid;
  • Azilsartan;
Formula:C25H20N4O5
Exact Mass:456.14300

 

GlitterGlitterGlitterGlitter

1H NMR PREDICT
2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid NMR spectra analysis, Chemical CAS NO. 147403-03-0 NMR spectral analysis, 2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid H-NMR spectrum
 

GlitterGlitterGlitterGlitter
13 C NMR PREDICT
2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid NMR spectra analysis, Chemical CAS NO. 147403-03-0 NMR spectral analysis, 2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid C-NMR spectrum
 

GlitterGlitterGlitterGlitter

AZILSARTAN MEDOXIMIL
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate
CAS No.:863031-21-4
Synonyms:
View More
  • Azilsartan Medoxomil;
  • Azilsartan (medoxomil);
  • Azilsartan;
  • azilsartan medoxomilo;
  • azilsartanum medoxomilum;
  • UNII-LL0G25K7I2;
  • (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate;
  • [14C]-Azilsartan medoxomil;
  • Edarbi;
  • TAK 491;
  • Azilsartan kamedoxomil;
  • (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester of 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]methyl]-2-ethoxy-1H-benzimidazole-7-carboxylic acid;
Formula:C30H24N4O8
Exact Mass:568.15900
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate NMR spectra analysis, Chemical CAS NO. 863031-21-4 NMR spectral analysis, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate H-NMR spectrum






GlitterGlitterGlitterGlitter
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate NMR spectra analysis, Chemical CAS NO. 863031-21-4 NMR spectral analysis, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate C-NMR spectrum


GlitterGlitterGlitterGlitter
Cited Patent
Filing datePublication dateApplicantTitle
WO2012107814A1 *Jan 24, 2012Aug 16, 2012Jubilant Life Sciences LimitedAn improved process for the preparation of azilsartan medoxomil
US5243054 *Jun 25, 1992Sep 7, 1993Takeda Chemical Industries, Ltd.Compound which is angiotensin ii antagonist
US20050187269 *Jan 7, 2005Aug 25, 2005Takeda Pharmaceutical Company LimitedBenzimidazole derivative and use thereof
Citing PatentFiling datePublication dateApplicantTitle
WO2013186792A2 *Jun 6, 2013Dec 19, 2013Msn Laboratories LimitedProcess for the preparation of (5-methyl-2-oxo-l,3-dioxoi-4-vl)methvl 2- ethoxv-l-{[2'-(5-oxo-4,5-dihvdro-l,2,4-oxadiazol-3-vl)biphenyi-4-vl]methyl}- lh-benzimidazole-7-carboxyiate and its salts




REFERENCES
[1] M. Gasparo, K. J. Catt, T. Inagami, J.W. Wright, T. Unger, Pharmacol. Rev.2000, 52, 415
[2] W.B. White, M.A. Weber, D. Sica, G.L. Bakris,A. Perez,C. Cao, S. Kupfer, Hypertension.2011, 57, 413.
[3] G.L.Bakris, D.Sica, M.Weber, W.B. White,A. Roberts,A. Perez, C. Cao, S. J. Kupfer, Clin. Hypertens.2011, 13, 81.
[4] D. Sica, W.B. White, M.A. Weber, G.L. Bakris, A. Perez,C. Cao,A. Handley, S. Kupfer, J. Clin. Hypertens. 2011, 13, 467.
[5] H. Rakugi, K. Enya, K. Sugiura, Y. Ikeda, Hypertens. Res.2012, 35, 552.
[6] Y. Kohara, E. Imamiya, K. Kubo, T. Wada, Y. Inada, T. Naka, Bioorg. Med. Chem. Lett.1995, 5, 1903.
[7] T. Naka,Y. Inada, U.S. Patent 5583141 (1996) [8] T. Naka, Y. Inada, Eur Pat. Appl. EP 0520423, (1992)
[9] Y. Kohara, K. Kubo,E. Imamiya, T. Wada, Y. Inada, T. Naka, J. Med. Chem.1996, 39, 5228.
[10] T. Kuroita, H. Sakamoto,M.Ojima, U.S. Pat. Appl. 0187269 (2005) [11] T. Kuroita, H. Sakamoto, M. Ojima, U.S. Pat. Appl. 7157584 (2007) [12] S. Radl, J. Cerny,J. Stach, Z. Gablíkova, Org. Process Res. Dev.2013, 17, 77
[13] A. Agarwal, D. Bansal, A.S. Choudhary, S.K. Dubey, H. Mishra, D. Vir, WO 2012107814 A8 (2012)
[14] S.D. Dwivedi, K.K. Singh, J.T. Gajera, US 20140113942 A1, (2014)
[15] D. Bansal,H. Mishra,S.K. Dubey, A.S. Choudhary, D. Vir, A. Agarwal, A. Daz, US 20130317230 A1 (2013)
[16] International Conference of Harmonization (ICH). Q3A(R) Related substance/Impurities in New Drug Substance, Feb. 2002.



GlitterGlitterGlitterGlitter


 KARACHI, PAKISTAN


Map of karachi city






Image result for KARACHI

 
 Skyline of Karachi as seen from the I.I. Chundrigar Road.





 

 

 Karachi Municipal Corporation Building situated at M.A Jinnah Road and a sight of Downtown Karachi.



 

 


 Karachi is called the “City of Lights” by Pakistani people. Enjoy the majesty of Karachi; the birth place of Quaid-e-Azam Muhammad Ali Jiannah


 

 




 




No comments:

Post a Comment