A) BRIEF RESUME OF THE INTENDED WORK:
Ritodrine is a good tocolytic agent1.Chemically it is N-[2-(p-hydroxy phenyl) ethyl]-N-[2-(p-hydroxyphenyl)-2-hydroxy-1-methyl ethyl] amine. It is a sympathomimetic, a beta-2 receptor agonist and a phenyl ethyl amine derivative4.
The clearest indication of uterine relaxants is to delay or prevent premature parturition in selected individuals and to slow or arrest delivery for brief periods in order to under take other therapeutic measures. Tocolytic agents that are currently in use include beta-2 adrenergic agonist, magnesium sulfate and ethanol. Among beta-2 adrenergic agonist, currently, only Ritodrine is approved for the use of treatment of premature labor20.
At intolerable concentration, magnesium sulfate produces progressive inhibition of cardiac conduction and neuromuscular transmission. It also
Leads to respiratory depression and cardiac arrest20. Neonatal depression can also occur. The prolonged administration of magnesium salts may produce congenital rickets due to suppression of fetal parathyroid gland.
Ethanol may be nearly as effective as Ritodrine in prolonging gestation, but it does not produce a corresponding reduction in the incidence of fetal respiratory distress20.
Because of the above disadvantages of magnesium sulfate and ethanol, they are replaced by beta-2 adrenergic agonist i.e., Ritodrine. A survey of literature revealed that Ritodrine posses a good potential and biological activity. But Ritodrine does have some contraindication as, its use is complicated by the expected cardiovascular effects, including tachycardia, hypotension. There is also a continuous need for new tocolytic synthetic drugs with lesser side effects and potent activity for the management of preterm labor.
This has prompted us to synthesize and study the different derivatives of Ritodrine.
B) MATERIALS AND METHODS:
Ι) The present work is an attempt to,
1. Synthesize Ritodrine a potent tocolytic.
2. To characterize these derivatives using various analytical techniques
Like TLC, Melting Point, IR, NMR and MASS Spectroscopy.
ΙΙ) Scheme:
SYNTHESIS OF RITODRINE
The method comprises bromination of the appropriate amount of 4 benzoyl oxy propio phenone to produce 4 benzoyl oxy bromo propio phenone (I). The compound (I) on reaction with 2-(4 benzyloxy phenyl) ethylamine forms an intermediate which on reduction with hydrogen in presence of palladium gives Ritodrine.
C) LIST OF REFERENCES:
1) Merck Index, 14th Edition, 2006; 8237:1422.
2) Remington. The science and practice of Pharmacy, 20th Edition, 1980; 1310.
3) Wilson and Gisvold.Text book of organic medicinal & Pharmaceutical chemistry. John H. Block, John N. Beale.11th edition. Lippincott Williams and Wilkins, N Y& London.2004; 528, 530-1.
4) Burger A. Medicinal Chemistry and Drug Discovery. Donald J.Abraham.6th edition.John Wiley and sons, Inc, New Jersey. 2003; 6:30.
5) Vogel. Text book of Practical Organic Chemistry.B.S Furniss, A.J Hannaford, P.W. G Smith, A.R.Tatchell. 5th edition. Pearson Education Ltd & Darling Kindersley Publishing Inc.1989; 1273.
6) British PharmaCopocia. 2005; (2): 1741-2.
7) Brashear WT, Kuhnert BR, Wei R. Structural Determination of the conjugated metabolites of Ritodrine. American Society for P’cology and experimental therapeutic 1990; 18(4): 488-93
8) Anne D. Walling. Comparing glyceril Trinitrate and Ritodrine in tocolysis. American Family Physician 2000 Jan 15.
9) Hosakere D. Revana Siddappa, Bochhe Gowda Manju. Spectro Photometric Determination of Ritodrine Hydrochloride and its applications to pharmaceutical preparations. II Farmaco 2001 Aug; 56(8); 615-9.
10) Naidu G. Krishnamurthy, Sudarshan K, Suresh Kumar K, Rekha D. Simple sensitive spectrometric determination of Ritodrine hydrochloride and isoniazid. J Analytical chemistry 2005 Sep; 60, #9; 822-7.
11) Philips NV, Glocilampenfa Bricken. Method of preparation of Ritodrine. Belg.660, 244, 1965 Aug; Neth. Appl.1964 Feb 27; 12pp.
12) Kuo-Changchin, Yuch-Ngo Wang, Pin Hsu. Neuropharmacological action of Ritodrine. Yao Hsueh Hsueh Pao 11(11), 756-61(1964).
13) Jacobus F. Vanstaden, Negussie W. Beyene, Raluca-Ioana Stefan, Hassan Y. Aboul- Enein. Spectrophotometric determination of Ritodrine hydrochloride using 4-amino antipyrine. 13th International conference on flow injection analysis-ICFIA. Talanta 2005 Dec 15; 68(2); 401-5.
14) Viswanathan CL, Kodgule MM, Chaudhari AR. Design synthesis and Evaluation of racemic 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl] amino-1-propanol hydrochlorides. Bioorganic and Medicinal Chemistry Lett 2005 Aug 1st; 15(15); 3532-5.
15) Gander R, DeZoeten LW, Vander JB. Schoot. Serum level of Ritodrine in Man. Eur J Clinical Pharmacology 1980 March; 17, #2.
16) Li Shei Lin, Lank. Wong Steve N. Caritis. Analysis of Ritodrine on serum by high-performance liquid chromatography with electrochemical detection. Digital Object Identifier (DOI) 1982 Dec 12.
17) Yamazaki, Naoki, Fukuda, Yoshimasa, Shibazaki, Yoshiaki, Niizato, Tetsutasou, Kosugi, Isao, Yoshioka, Shin. (-)-Ritodrine, Therapeutic composition, use and method of prepation. US 5449694, 1995 Nov.
18) Merz, Walter (Lever Kusen, DE, US), Littmann, Martin (Lever Kusen, DE, US), Kraatz, Udo (Lever Kusen, DE,US), Mannheims, Christoph(Lever Kusen, DE, US). Method of preparation of optically active 1-phenylethylamines. US 6034278, 2000 March.
19) Rania S Bakry, Abdel Faltah M.El Walily, Saied F.Belal. Spectrophotometric determination of some phenolic sympathomimetic drugs through reaction with 2, 6-dihalo quinone chlorimides, J Microchemica Acta 1997 March; 127, #1-2; 89-93.
20) Goodman and Gilman’s. The pharmacological basis of therapeutics. 8th edition, Alfred Goodman Gilman, Theodore W. Rall, Alan S. Nies, Palmer Taylor, 1991; (2): 949-51.