Author Topic: Zolmitriptan Synthesis  (Read 2565 times)

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bunny

  • Guest
Zolmitriptan Synthesis
« on: September 26, 2000, 03:35:00 PM »
OK,

I realize this isn't a typical chemical synthesize, but I was wondering if anyone could help me out.

I would like to try synthesizing zolmiptriptan.  I had considered a couple of different methods and basically couldn't figure out how to put them together wihtout destroying the initial reactants.

http://www.eskimo.com/~robertc/synthesis/Synth1.html



So.....

Do any of you chemists have some ideas to help?  Or does anyone know where the best place to get the patented synthesis process would be.

Thanks in advance.

Rhodium

  • Guest
Re: Zolmitriptan Synthesis
« Reply #1 on: September 27, 2000, 01:26:00 PM »
Look up its synthesis in the Merck Index or something. Fusing that lactam with your indole isn't gonna happen.


http://rhodium.lycaeum.org


Alphabeta121

  • Guest
Re: Zolmitriptan Synthesis
« Reply #2 on: September 29, 2000, 03:21:00 AM »
Zolmitriptan ? why?

SPHYBRID

  • Guest
Re: Zolmitriptan Synthesis
« Reply #3 on: September 29, 2000, 04:12:00 AM »
Actually I might be able to find something on this. Zomig is a odd molecule in that it has a dmt counterpart and also a amphetamine counterpart.Here are some references I found on beilstein.

Substance
Registry Number   7415009Name   zolmitriptan   4-[3-(2-dimethylamino-ethyl)-1H-indol-5-ylmethyl]-oxazolidin-2-oneFormula   C16H21N3O2Weight   287.36Number   32270,  2817Type   heterocyclicID   6359198ID   7050302Reference   6-27Date   1996/04/26Date   1998/03/04
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Pharmacological Data 1 of 3
1    contraction of the New Zealand white rabbit saphenous vein, pD&2%: 6.1; maximum contraction relative to 5-HT, 1.48. 1    6048434; Journal; Perez, M.; Ayerbe, N.; Fourrier, C.; Sigogneau, I.; Pauwels, P. J.; et al.; EJMCA5; Eur.J.Med.Chem.Chim.Ther.; EN; 32; 2; 1997; 129-134;
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Pharmacological Data 2 of 3
1    binding affinities at cloned human receptors, K&i% (nM): 5-HT&1D$a% - 0.92, 5-HT&1D$b% - 4.2, 5-HT&1A% - 78.6; inhibition of forskolin-induced cAMP formation in a stably transfected CHO-K1 cell line, EC50: 15.7 nM. 1    6048434; Journal; Perez, M.; Ayerbe, N.; Fourrier, C.; Sigogneau, I.; Pauwels, P. J.; et al.; EJMCA5; Eur.J.Med.Chem.Chim.Ther.; EN; 32; 2; 1997; 129-134;
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Pharmacological Data 3 of 3
1    binding affinities at cloned human 5-HT&1D$a%, 5-HT&1D$b% (EC50=15 nM) and 5-HT&1A% receptors; functional activity: contraction of the New Zealand white rabbit saphenous vein. 1    6001415; Journal; Perez, Michel; Fourrier, Catherine; Sigogneau, Isabelle; Pauwels, Petrus J.; Palmier, Christiane; et al.; JMCMAR; J.Med.Chem.; EN; 38; 18; 1995; 3602-3607;


Reaction
ID   4337486BRN   1209228 formaldehyde   7414433 (S)-2-<5-<(2-oxo-1,3-oxazolidin-4-yl)methyl>-1H-indol-3-yl>ethylamineBRN   7415010 4-[3-(2-dimethylamino-ethyl)-1H-indol-5-ylmethyl]-oxazolidin-2-one. of Reaction Details   1
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Reaction Details
Classification   Preparation   31 percent (BRN=7415010)   NaCNBH3, glacial AcOH   methanolConditions   Ambient temperature. 1    6001396; Journal; Glen, Robert C.; Martin, Graeme R.; Hill, Alan P.; Hyde, Richard M.; Woollard, Patrick M.; et al.; JMCMAR; J.Med.Chem.; EN; 38; 18; 1995; 3566-3580;


Citation Number
Number   6001396
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Citation
Type   Journal   Glen, Robert C.; Martin, Graeme R.; Hill, Alan P.; Hyde, Richard M.; Woollard, Patrick M.; et al.   JMCMARTitle   J.Med.Chem.Code   EN(Series) Volume   38   18Year   1995   3566-3580
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Abstract
   Computer-Aided Design and Synthesis of 5-Substituted Tryptamines and Their Pharmacology at the 5-HT&1D% Receptor: Discovery of Compounds with Potential Anti-Migraine Properties   The design and synthesis of a series of novel 5-substituted tryptamines with pharmacological activity at 5-HT&1D% and other monoamine receptors is described.Structural modifications of N- and C-linked (prinicipally hydantoin) analogues at the 5-position were synthesized and their pharmacological activities were utilized to deduce significant steric and electrostatic requirements of the 5-HT&1D% and 5-HT&2A% receptor subtypes.Conformations of the active molecules were computed which, when overlaid, suggested a pharmacophore hypothesis which was consistent with the affinity and selectivity measured at 5-HT&1D% and 5-HT&2A% receptors.This pharmacophore is composed of a protonated amine site, an aromatic site, a hydrophobic pocket, and two hydrogen-bonding sites.A 'selectively site' was also identified which, if occupied, induced selectivity for 5-HT&1D% over 5-HT&2A% in this series of molecules.The development and use of the pharmacophore models in compound design is described.In addition, the physicochemical constraints of molecular size and hydrophobicity required for efficient oral absorption are discussed.Utilizing the pharmacophore model in conjuction with the physicochemical constraints of molecular size and log D&pH7.4% led to the discovery of 311C90 (6), a new selective 5-HT&1D% agonist with good oral absorption and potential use in the treatment of migraine.   EN
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Substance 1 of 158
Registry Number   110598Preferred RN   461-72-3Registry Number   461-72-3Name   imidazolidine-2,4-dione   hydantoin   imidazolidine-2,4-dioneFormula   C3H4N2O2Weight   100.08Number   28774Type   heterocyclicID   93436ID   121314Reference   0-24-00-00242,  1-24-00-00287,  2-24-00-00127,  4-24-00-01034,  5-24-05-00188,  6-24Date   1988/06/27Date   2000/03/07
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Substance 2 of 158
Registry Number   125513Preferred RN   61-54-1Registry Number   61-54-1Name   2-indol-3-yl-ethylamine   2-Indol-3-yl-aethylamin   1H-indole-3-ethanamine   tryptamine   2-(1H-indol-3-yl)-ethylamineFormula   C10H12N2Weight   160.22Number   27417Type   heterocyclicID   127263ID   161480Reference   2-22-00-00346,  4-22-00-04319,  5-22-10-00045,  6-22Date   1988/06/27Date   2000/03/10
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Substance 3 of 158
Registry Number   134111Preferred RN   1821-47-2Registry Number   1821-47-2Name   2-(5-methyl-indol-3-yl)-ethylamine   2-(5-Methyl-indol-3-yl)-aethylamin   2-(5-methyl-1H-indol-3-yl)-ethylamineFormula   C11H14N2Weight   174.25Number   27419Type   heterocyclicID   148589ID   168329Reference   4-22-00-04364,  5-22-10-00166,  6-22Date   1988/06/27Date   2000/03/07
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Substance 4 of 158
Registry Number   160628Preferred RN   487-93-4Registry Number   487-93-4Name   3-(2-dimethylamino-ethyl)-indol-5-ol   3-(2-Dimethylamino-aethyl)-indol-5-ol   3-[2-(dimethylamino)ethyl]-1H-indol-5-ol   Bufotenin   3-(2-dimethylamino-ethyl)-1H-indol-5-olFormula   C12H16N2OWeight   204.27Number   27626,  2817Type   heterocyclicID   162163ID   168757Reference   0-22-00-00499,  4-22-00-05671,  5-22-12-00026,  6-22Date   1988/06/27Date   2000/03/03
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Substance 5 of 158
Registry Number   237397Registry Number   68319-44-8,  103273-88-7,  123944-77-4Name   5-(4-nitro-benzyl)-imidazolidine-2,4-dione   5-(4-nitro-benzyl)-imidazolidine-2,4-dioneFormula   C10H9N3O4Weight   235.20Number   28851Type   heterocyclicID   196953ID   245163Reference   1-24-00-00346,  4-24-00-01471,  5-24-08-00060,  6-24Date   1988/06/27Date   1997/02/03
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