Isochroman-6-carboxamides as highly selective 5-HT(1D) agonists: Potential new treatment for migraine without cardiovascular side effects [2]

Journal of Medicinal Chemistry

Volumn 41, Issue 13, 1998, Pages 2180-2183

  Ennis, Michael D ^a,b   Ghazal, Nabil B ^a,b   Hoffman, Robert L ^a,b   Smith, Martin W ^a,c   Schlachter, Siusaidh K ^a,c   Lawson, Charles F ^a,c   Im, Wha Bin ^a,d   Pregenzer, Jeffrey F ^a,b   Svensson, Kjell A ^a,d   Lewis, Richard A ^a,d   Hall, Edward D ^a,d   Sutter, Dorothy M ^a,d   Harris, Lorri T ^a,e   McCall, Robert B ^a,e  

^a PFIZER INC   (United States)

^b Struct Analyt/Med Chemistry

^c Discovery Technologies   (United States)

^d CNS Diseases Research

^e Cardiovascular Pharmacology

Author keywords

[No Author keywords available]

Indexed keywords

ISOCHROMAN DERIVATIVE; SEROTONIN AGONIST; SUMATRIPTAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; BINDING AFFINITY; CARDIOVASCULAR RESPONSE; CAT; CONTROLLED STUDY; DRUG EFFECT; DRUG POTENCY; DRUG RECEPTOR BINDING; LETTER; MIGRAINE; NONHUMAN; RECEPTOR AFFINITY;

ANIMALS; BENZOPYRANS; BIOLOGICAL AVAILABILITY; BLOOD PRESSURE; BRAIN; CAPILLARY PERMEABILITY; CAROTID ARTERIES; CATS; CELL LINE; DRUG EVALUATION, PRECLINICAL; DURA MATER; GORILLA GORILLA; GUINEA PIGS; HYPOTHERMIA; INFLAMMATION; MIGRAINE DISORDERS; PIPERAZINES; RECEPTOR, SEROTONIN, 5-HT1D; RECEPTORS, SEROTONIN; SEROTONIN AGONISTS; STEREOISOMERISM; SUMATRIPTAN; VASCULAR RESISTANCE; VASOCONSTRICTOR AGENTS;

EID: 10744227604     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980137o     Document Type: Letter

References (24)

1. Olesen, J. Migraine and other headaches: the vascular mechanisms; Raven Press: New York, 1991.
2. Mushet, G. R.; Miller, D.; Clements, B.; Pait, G.; Gutterman, D. L. Impact of Sumatriptan on Workplace Productivity, Nonwork Activities, and Health-Related Quality of Life Among Hospital Employees With Migraine. Headache 1996, 36, 137-143.
3. de Lissovoy, G.; Lazarus, S. S. The economic cost of migraine. Neurology 1994, 44 (suppl. 4), S56-S62.
4. Osterhaus, J. T.; Gutterman, D. L.; Plachetka, J. R. Healthcare resource and lost labour costs of migraine headache in the US. Pharmacoeconomics 1992, 2, 67-76.
5. 1Dβ. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 3630-3634.
6. 1D receptor subtypes. Trends Pharmacol. Sci. 1996, 17, 103-105.
7. 1Dα serotonin receptor gene expression in trigeminal ganglia: Implications for antimigraine drug development Proc. Natl Acad. Sci. U.S.A. 1994, 91, 3666-3669.
8. Moskowitz, M. A.; Macfarlane, R. Neurovascular and molecular mechanisms in migraine headaches. Cerebrovasc. Brain Metab. Rev. 1993, 5, 159-177.
9. 1D Receptors: pharmacology and therapeutic potential. Serotonin 1996, 1, 19-29.
10. 1Dβ' receptors. Eur. J. Pharmacol. 1993, 242, 75-82.
11. Branchek, T.; Audia, J. E. Recent Advances in Migraine Therapy. Annu. Rep. Med. Chem. 1997, 32, 1-10.
12. TenBrink, R. E.; Bergh, C. L.; Duncan, J. N.; Harris, D. W.; Huff, R. M.; Lahti, R. A.; Lawson, C. F.; Lutzke, B. S.; Martin, I. J.; Rees, S. A.; Schlachter, S. K.; Sih, J. C.; Smith, M. W. (S)-(-)- 4-[4-[2-(Isochroman-1-yl)ethyl]-piperazin-1-yl]benzenesulfonamide, a Selective Dopamine D4 Antagonist. J. Med. Chem. 1996, 39, 2435-2437.
13. 1D receptors cloned from chimpanzee, gorilla, and rhesus monkey in comparison with those from the human and guinea pig receptors. Neurosci. Lett. 1997, 235, 117-120.
14. The acid (S)-(-)-4 was assayed for optical purity by reduction to the corresponding alcohol and analysis via HPLC (Chiracel OJ column; see Supporting Information for details). The ester (R)-(+)-3 was hydrolyzed to the corresponding acid (R)-(+)-4 and assayed in an identical fashion. A single recrystallization of this enriched chiral acid brought the optical purity to 99%.
15. Davidsen, S. K.; May, P. D.; Summers, J. B. Di-tert-butyl N-acylimido dicarbonates as isolable acylating agents: Mild conversion of primary carboxamides to substituted amides. J. Org. Chem. 1991, 56, 5482-85.
16. 1D receptors fails because these receptors appear to be poorly coupled to intracellular G-proteins when expressed in HEK 293 cells (Wha Bin Im, manuscript in preparation).
17. 1D receptors causes hypothermia in the guinea pig. J. Psychopharmacol. 1994, 8, 14-21.
18. 1B (350- 400-fold).
19. Moskowitz, M. A.; Cutrer, F. M.; Lee, W. S.; Waeber, C.; Limmroth, V.; Yu, X. Drug Discovery in Migraine Circa 1995. In Experimental Headache Models; Olesen, J., Moskowitz, M. A., Eds.; Lippincott-Raven Publishers: Philadelphia, 1995; pp 63-73.
20. Markowitz, S.; Saito, K.; Moskowitz, M. A. Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain. J. Neurosci. 1991, 7, 4129-4136.
21. Buzzi, M. G.; Moskowitz, M. A. The antimigraine drug sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. Br. J. Pharmacol. 1990, 99, 202-206.
22. 1D receptor agonist, on electrically induced durai plasma extravasation and capsaicin-evoked c-Fos immunoreactivity within trigeminal nucleus caudalis. Neuropharmacology, submitted.
23. Carotid artery resistance was determined by dividing carotid blood flow (as measured by an implanted transit-time ultrasonic probe) by mean arterial blood pressure. Complete details are provided in the Supporting Information.
24. We thank Ms. Grace Wilson, Endocrine Pharmacology and Metabolism, Pharmacia & Upjohn, for this determination.