Eletriptan

Common name: Eletriptan; UK-116044; Relpax; Eletriptan hydrobromide
Trademarks: Relpax
Molecular Formula: C22H26N2O2S
CAS Registry Number: 143322-58-1
CAS Name: 5-[2-(benzenesulfonyl)ethyl]-3-{[(2R)-1-methylpyrrolidin-2-yl]methyl}-1H-indole
Molecular Weight: 382.519
SMILES: CN1CCC[C@@H]1CC1=CNC2=C1C=C(CCS(=O)(=O)C1=CC=CC=C1)C=C2
InChI Key: PWVXXGRKLHYWKM-LJQANCHMSA-N
InChI: InChI=1S/C22H26N2O2S/c1-24-12-5-6-19(24)15-18-16-23-22-10-9-17(14-21(18)22)11-13-27(25,26)20-7-3-2-4-8-20/h2-4,7-10,14,16,19,23H,5-6,11-13,15H2,1H3/t19-/m1/s1
Activity: Anti-migraine Agents; Serotonin Antagonists; Serotonin Receptor Agonists;  5-Hydroxytryptamine 1B/1D Receptor Agonist; 5-HT1B Receptor Agonist
Status: Launched 2002
Originator: Pfizer

Eletriptan synthesis: US5545644A (oldest synthesis reference)

Eletriptan synthesis: US7288662B2 (improvement on the earlier synthesis, removes the problem due to dimerization in the above synthesis. Loved by Pfizer, not so by others !!!!)

Eletriptan synthesis: WO2005103035A1

References:

1. Macor, J. E.; et. al. Indole derivatives. US5545644A

2. Ogilvie, R. J. Process for the preparation of eletriptan. US7288662B2

3. Ashcroft, C.P. Modified fischer indole synthesis of eletriptan. WO2005103035A1

For more drugs and their synthesis: Synayurajan database

Frovatriptan

Common name: Frovatriptan; SB-209509; VML-251; Frovatriptan Succinate
Trademarks: Frova
Molecular Formula: C14H17N3O
CAS Registry Number: 158747-02-5; 158930-18-8 ((S)-isomer), 158747-09-2 (racemate), 158930-17-7 (succinate)
CAS Name: (3R)-3-(methylamino)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamide
Molecular Weight: 243.304
SMILES: CN[C@@H]1CCC2=C(C1)C1=C(N2)C=CC(=C1)C(N)=O
InChI Key: XPSQPHWEGNHMSK-SECBINFHSA-N
InChI: InChI=1S/C14H17N3O/c1-16-9-3-5-13-11(7-9)10-6-8(14(15)18)2-4-12(10)17-13/h2,4,6,9,16-17H,3,5,7H2,1H3,(H2,15,18)/t9-/m1/s1
Activity: Treatment of  Migraines; Serotonin Antagonists; Serotonin Receptor Agonists; Anti-migraine Agents; Affinity for 5-HT1B/1D Receptors; Treatment of Menstrual Migraine
Status: Launched 2001
Originator: SmithKline;Vernalis/Elan

It appears SKB has filed many patents for this compound with same procedure repeated in them. The difference is few patents have other derivatives, and/or different racemic resolution schemes.

Frovatriptan synthesis: WO1993000086A1

Frovatriptan synthesis: US5616603A

Frovatriptan synthesis: US5618948A

References:

1. Gaster, L. M.; et. al. Use of tetrahydrocarbazone derivatives as 5ht1 receptor agonists. WO1993000086A1

2. Borrett, G. T.; et. al. Treating migraines. US5616603A

3. Borrett, G. T.; et. al. Treatment of 6-carboxamido-3-methylamino-1,2,3,4-tetrahydrocarbazole with 2-pyrrolidone-5-carboxylic acid, crystallization. US5618948A

4. Markus, F.; et. al. Frovatriptan review. Expert Opin Pharmacother 2007, 8(17), 3029-3033. (activity)

5. Kelman, L. Review of frovatriptan in the treatment of migraine. Neuropsychiatr Dis Treat 2008, 4(1), 49-54. (activity)

For more drugs and their synthesis: Synayurajan database

Almotriptan

Common name: Almotriptan; LAS-31416; Axert; Almotriptan Malate
Trademarks: Axert; Almogran; Almotrex; Amignul
Molecular Formula: C17H25N3O2S
CAS Registry Number: 181183-52-8
CAS Name: dimethyl(2-{5-[(pyrrolidine-1-sulfonyl)methyl]-1H-indol-3-yl}ethyl)amine
Molecular Weight: 335.464
SMILES: CN(C)CCC1=CNC2=C1C=C(CS(=O)(=O)N1CCCC1)C=C2
InChI Key: WKEMJKQOLOHJLZ-UHFFFAOYSA-N
InChI: InChI=1S/C17H25N3O2S/c1-19(2)10-7-15-12-18-17-6-5-14(11-16(15)17)13-23(21,22)20-8-3-4-9-20/h5-6,11-12,18H,3-4,7-10,13H2,1-2H3
Activity: Treatment of  Migraines; Serotonin Antagonists; Serotonin Receptor Agonists; Anti-migraine Agents
Status: Launched 2001
Originator: Almiral/Janssen

Almotriptan synthesis: Scheme 1 [Tetrahedron 2001, 57(6), 1041-1048 (also Ref. 2)]

Almotriptan synthesis: Scheme 2 (Tetrahedron 2001, 57(6), 1041-1048) 

Almotriptan synthesis: Scheme 3 (Tetrahedron 2001, 57(6), 1041-1048)

Almotriptan synthesis: US5565447A

Almotriptan synthesis: WO2006129190A1

References:

1. Bosch, J.; et. al. Synthesis of 5-(sulfamoylmethyl)indoles. Tetrahedron 2001, 57(6), 1041-1048.

2.  Fernandez, M.-D.; et. al. ES2084560B1

3.  Forner, D. F.; et. al. Almotriptan malate; treating headaches, movement disorders, depression, anxiety. US5565447A

4. Pradhan, N. S. C.; et. al. Process for the preparation of almotriptan. WO2006129190A1

5. Keam, S. J.; et. al. Almotriptan: a review of its use in migraine. Drugs 2002, 62(2), 387-414. (activity)

6. Pascual, J.; et. al. Almotriptan: a review of 10 years' clinical experience. Expert Rev Neurother 2010, 10(10), 1505-1517. (activity)

7. Gras, J.; et. al. Almotriptan, a new anti-migraine agent: a review. CNS Drug Rev 2002, 8(3), 217-234. (activity)

For more drugs and their synthesis: Synayurajan database