United States Patent (19) 11 Patent Number: 6,071,970 Mueller Et Al
Total Page:16
File Type:pdf, Size:1020Kb
USOO607 1970A United States Patent (19) 11 Patent Number: 6,071,970 Mueller et al. (45) Date of Patent: Jun. 6, 2000 54) COMPOUNDS ACTIVE ATA NOVELSITE WOA 93 ON RECEPTOR-OPERATED CALCUM O4373 3/1993 WIPO. CHANNELS USEFUL FOR TREATMENT OF 9521612 8/1995 WIPO. NEUROLOGICAL DISORDERS AND 9605818 2/1996 WIPO. DISEASES 964OO97 12/1996 WIPO. OTHER PUBLICATIONS 75 Inventors: Alan L. Mueller, Salt Lake City; Manuel F. Balandrin, Sandy; Marcusson, Jan O., et al., “Inhibition of Hparoxetine Bradford C. VanWagenen, Salt Lake binding by various Serotonin uptake inhibitors: Structure City; Eric G. DelMar, Salt Lake City; activity-relationships”, European Journal of Pharmacol Scott T. Moe, Salt Lake City; Linda D. ogy, 215, 1992, 191-198. Artman, Salt Lake City; Robert M. Chemical Abstracts, vol. 69, 1968, p. 3322. Barmore, Salt Lake City, all of Utah Chemical Abstracts, vol. 67, 1967, p. 3059. Chemical Abstracts, vol. 66, 1967, p. 4375. 73 Assignee: NPS Pharmaceuticals, Inc., Salt Lake Chemical Abstracts, vol. 5, p. 423, 1959. City, Utah Williams, Ifenprodil Discriminates Subtypes of the N-meth yl-D-asparate Receptor: Selectivity and Mechanisms at 21 Appl. No.: 08/485,038 Recombinant Heteromeric Receptors, Mol. Pharmacol., 44: 851, 1993). 22 Filed: Jun. 7, 1995 Wiley and Balster, Preclinical Evaluation of N-Methyl D-aspartate Antagonists for Antianxiety Effects: a Review Related U.S. Application Data In: Multiple Sigma and PCP Receptor Ligands; Mechanisms 63 Continuation-in-part of application No. PCT/US94/12293, for Neuromodulation and Neuroprotection NPP Books, Ann Oct. 26, 1994, which is a continuation-in-part of application Arbor, Michigan pp. 801-815, 1992. No. 08/288,668, Aug. 9, 1994, abandoned, which is a Ginsberg and Busto, Rodent Models of Cerebral Ischemia, continuation-in-part of application No. 08/194.210, Feb. 8, Stroke, 20:1627, 1989. 1994, abandoned, which is a continuation-in-part of appli Karpiak et al., “Animal Models for the Study of Drugs in cation No. 08/014,813, Feb. 8, 1993, abandoned. Ischemic Stroke', Ann. Rev. Pharmacol. Toxicol, 29:403, 51) Int. Cl." ........................ A61K31/135; CO7C 211/03 1989. 52 U.S. Cl. .......................... 514/648; 514/183; 514/210; Willetts et al., “The Behavioral Pharmacology of NMDA 514/212; 514/315; 514/408; 514/428; 514/645; Receptor Antagonists' Trends Pharmacol. Sci., 11:423, 514/646; 514/653; 514/654; 564/315; 564/316; 1990. 564/319 Olney, et al., “Pathological Changes Induced in Cerebrocor 58 Field of Search ..................................... 514/645, 648, tical Neurons by Phencyclidine and Related Drugs”, Sci 514/183,210, 212, 408, 428, 315, 646, ence, 244: 1360, 1989. 653, 654; 564/315, 316, 319 Snell and Johnson, “In: Excitatory Amino Acids in Health and Disease”, John Wiley and Sons, p. 261, 1988. 56) References Cited Collingridge and Davis, In. The NMDA Receptor, IRL Press. p. 123, 1989. U.S. PATENT DOCUMENTS Rogawski, “Therapeutic Potential of Excitatory Amino Acid 3,372,193 3/1968 Moffett et al. .......................... 564/375 Antagonists: Channel Blockers and 2,3-benzodiazepines', 4,018,895 4/1977 Molloy et al. ... ... 514/651 Trends Pharmacol. Sci., 14:325, 1993. 4,313,896 2/1982 Molloy et al. ....... ... 564/347 Nason, et al., “Synthesis of Neurotoxic Nephila Spider 5,037,846 8/1991 Saccomano et al. .... ... 514/419 Venoms: NSTX-3 and JSTX-3”, Tetrahedron Lett., 5,145,870 9/1992 Jakobsen et al. ........ ... 514/524 30:2337, 1989. 5,185.369 2/1993 Saccomano et al. ... 514/5O2 Scatton et al., “NMDA Receptor Antagonists: Treatment for 5,310,756 5/1994 Jakobsen et al. ....................... 514/524 Brain Ischemia,” Drug News & Perspectives 4(2):89-95 FOREIGN PATENT DOCUMENTS (1991). 0 005 658 4/1979 European Pat. Off.. (List continued on next page.) 0208523 4/1986 European Pat. Off.. 0399.504 5/1990 European Pat. Off.. Primary Examiner Richard L. Raymond A 0436 332 7/1991 European Pat. Off.. Attorney, Agent, or Firm-Lyon & Lyon LLP 1051 281 2/1959 Germany. A300541 6/1964 Netherlands. 57 ABSTRACT A 33 285 12/1964 Netherlands. A 4239816 6/1994 Netherlands. Method and compositions for treating a patient having a 1 169944 7/1967 United Kingdom. neurological disease or disorder, Such as Stroke, head 1134715 11/1968 United Kingdom. trauma, Spinal cord injury, epilepsy, anxiety, or neurodegen 1135926 12/1968 United Kingdom. erative diseaseS Such as Alzheimer's Disease, Huntington's 9214709 3/1992 WIPO. WOA 93 Disease, Parkinson's Disease, or amyotrophic lateral Scle 04036 3/1993 WIPO. rosis (ALS). WOA 93 O4041 3/1993 WIPO. 185 Claims, No Drawings 6,071,970 Page 2 OTHER PUBLICATIONS Helke, C.J., et al., Antiextensor Effects of 3, 3-Diphenyl -n-Propylamine in Mouse, European Journal of Pharma Burtsev and Savkov, “Calcium Antagonists (Finoptin and cology, vol. 48, No. 3, 1978, pp. 231-235. Senzit) in the Treatment of Cerebrovascular Disorders,” Gisvold, S.E., et al., “Drug Therapy in Brain Eschaemia', Klinicheskaia Meditsina 67(9):51-54 (1989) (abstract from British Journal of Anesthesia, vol. 57, No. 1 1985, pp. Medline). 96-109. Cramer et al., “Kalinic Acid and 4-Aminopyridine Seizure Donevan et al. “GYKI 52466, A 2,3-Benzodiazepine, Is A Models in Mice: Evaluation of Efficacy of Anti-Epileptic Highly Selective, Noncompetitive Antagonist Of AMPA/ Agents and Calcium Antagonists,” Life Sciences Kainate Receptor Responses” 10 Neuron 51, 1993. 54:271-275 (1994). Nakanishi et al. “Bioorganic Studies Of Transmitter Recep Fingl and Woodbury, Chapter 1, pp. 1-46 in The Pharma tors With Philanthotoxin Analogs’ Pure & Applied Chem cological Basis of Therapeutics (5th edition),eds. Goodman istry vol. 66, #3 (1994). et al., MacMillan Publishing Co., Inc., New York (1975). Williams, “Effects Of Agelenopsis Aperta Toxins. On The Foye et al., Principals of Medicinal Chemistry, 4th edition, N-Methyl-D-Aspartate Receptor: Polyamine-Like And Lea & Febiger/Williams and Wilkins, Philadelphia, PA, pp. High-Affinity Antagonist Actions' 266 The Journal of 233,265,281–282,340–341, 418-427 and 430 (1995). Pharmacology and Experimental Therapeutics 231, 1993. Melloni et al., “Potential antidepressant agents. C-Aryloxy Deneris et al. “Pharmacological And Functional Diversity benzyl derivatives of ethanolamine and morpholine,” Eur: J. Of Neuronal Nicotinic Acetylcholine Receptors' 12 Trends Med. Chem.–Chim. Ther. 19:235–242 (1984). In Pharmacol. Sci. 34, 1991. The Merck Index, 11th edition, Merck & Co., Inc., Rahway, Fisher et al. “Evolving Toward Effective Therapy For Acute New Jersey, p. 218 at No. 1433, p. 337 at No. 2180, p. 623 Ischemic Stroke” 270 JAMA 360, 1993. at No. 3916, p. 655 at No. 4112, p. 1148 at No. 7198, p. 1227 Honoré et al. “Ouinoxalinediones: Potent Competitive Non at No. 7744, p. 1444 at No. 9098, and p. 1597 at No. 10024 NMDA Glutamate Receptor Antagonists' 24 Science 701, (1989). 1988. Mikio et al., “Synthesis of Analgesics,” Chemical Abstracts, Herlitz et al. “Argiotoxin Detects Molecular Differences. In vol. 83, No. 7, Aug. 18, 1975 at abstract No. XP002016632. AMPA Receptor Channels” 10 Neuron 1131, 1993. Palmer et al., “Anticonvulsant Properties of Calcium Chan Raditsch et al. “Subunit-Specific Block Of Cloned NMDA nel Blockers in Mice: N-Methyl-D-, L-Aspartate- and Bay Receptors By Argiotoxins 324 FEBS Lett. 63, 1993. K8644 Induced Convulsions are Potentially Blocked by the Reynolds, J.E.F., “Martindale, The Extra Pharmacopoeia, Dihydropyridines,” Epilepsia 34:372-380 (1993). The Pharmaceutical Press, London “Terolidine” 1989, pp. Paul et al., “Adaptation of the N-Methyl-D-Aspartate 543-544. Receptor Complex Following Chronic Antidepressant Treat Leszkovszky G., et al., “The Pharmacology of Diphenyla ments,” J. Pharmacology and Experimental Therapeutics lkyl Derivatives' Acta Physiologica Academiae Scientiarum 269: 95-102 (1994). Hungaricae, vol. 29, 1996, pp. 283–298. Prous, The Year'Drug News, Therapeutic Targets, 1995 Blake, J.C., et al., 2-Methyl-3, Edition, Prous Science Publishers, Barcelona, Spain, pp. 13, 3-Diphenyl-3-Propanolamine (2-MDP) Selectively 55-56, 58-59, 74, 89, 144-145, 152, 296-297 and 317 Antagonises N-Methyl-Aspartate (NMDA), Pharmacology (1995). Biochemistry cc Behavior, vol. 24, No. 1, 1986, pp. 23-25. Buschauer, A., et al., Synthesis and Histamine H2 agonistic Scatchard, “The Attractions of Proteins For Small Molecules activity of arpromidine Analogues: Replacement of the and Ions.” Ann. N.Y. Acad. Sci. 51:660-672 (1949). Pheniramine-like Moiety by Non-Heterocyclic Groups, Williams, “Effects of Agelenopsis Aperta Toxins on the Eur: J. Med. Chem, 1992 27:321-330. N-Methyl-D-Aspartate Receptor: Polamine-Like and Keasling, Hugh H., et al., “Central Nervous System Agents' High-Affinity Antagonists Actions,” J. Pharmacol. Exp. Journal of Medicinal Chemistry, 1971, vol. 14, No. 11, pp. Therap. 266:231 (1993). 1106–1111. Chemical Abstracts Service, Registry Handbook, Reg. No. Beckett, A.H., et al., “Configurational Studies in Synthetic 114272-62-7 through 116231-28-8,(1988)Supplement. Analgesics”,J. Chem. Soc., 900(1955). Chemical Abstract 54:24555i (1960), 24555-245556. Camps, Francisco, et al., “New and Efficient One-Pot Prepa Chemical Abstract 54:424a (1960). ration of Alkyl Halides From Alcohols', Communications, Sutton, K.G., et al. “Inhibition of Voltage-Activated CA2+ May 1987, pp. 511–512. Currents from Cultured Sensory Neurones By Spermine, Reist, E.J., et al., “Sodium Azide in Dimethylformamide for Argiotoxin-636 and a Synthetic Arginine Polyamine” the Preparation of Amino-Sugars”, Chemistry and Industry, Molecular Neuropharmacology, vol. 3, 1993, pp. 37-43. Oct. 13, 1962, pp. 1794–1795. Blagbrough, I.S., et al., “Polyamine Amide Toxins as Phar Moffett, R.B., et al., “Central Nervous System Agents”, macological Tools and Pharmaceutical agents, Proceedings Journal of Medicinal Chemistry, 1971, vol. 14, No. 11, pp. of the Royal Society of Edinburgh, vol. 99, No. 1-2, 1992, 1088–1111. pp. 67-81. Tang, A.H., et al., Phencyclidine-Like Behavioral Effects of Artman, L.D., et al., “Preferential Inhibitory Effects of 2-Methyl-3,3-diphenyl-3-propanolamine (2-MDP), Phar Arylamine Spider Toxins on NMDA Receptor-Mediated macology Biochemistry cc Behavior, vol.