Novel M1 allosteric ligands: A patent review

Expert Opinion on Therapeutic Patents

Volumn 22, Issue 12, 2012, Pages 1385-1398

  Kuduk, Scott D ^a   Beshore, Douglas C ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Allosteric; Allosteric agonist; Allosteric modulator; M1; Modulators; PAM

Indexed keywords

1 [3 (4 BUTYLPIPERIDINO)PROPYL] 1,3 DIHYDROBENZIMIDAZOL 2 ONE 5; 77 LH 28 1; AC 260584; AC 42; BENZIMIDAZOLE DERIVATIVE; BENZOXAZOLE DERIVATIVE; CLOZAPINE; GSK 1034702; LU AE 51090; MUSCARINIC M1 RECEPTOR; MUSCARINIC M1 RECEPTOR AGONIST; NAPHTHALENE DERIVATIVE; NORCLOZAPINE; QUINOLIZIDINE DERIVATIVE; QUINOLIZIDINONE DERIVATIVE; UNCLASSIFIED DRUG; VU 0027414; VU 0029767; VU 0090157; VU 0119498; VU 0357017; VU 0364572; VU 0405562; VU 207811; XANOMELINE; LIGAND; MUSCARINIC AGENT; NEUROLEPTIC AGENT; NOOTROPIC AGENT;

ALLOSTERISM; ALZHEIMER DISEASE; AMNESIA; BINDING ASSAY; BINDING SITE; CALCIUM MOBILIZATION; CHOLINERGIC TRANSMISSION; DRUG BINDING SITE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CLEARANCE; DRUG EFFECT; DRUG EFFICACY; DRUG PENETRATION; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; FOREBRAIN; HUMAN; HYPERACTIVITY; IN VIVO STUDY; MEMORY DISORDER; NEUROMODULATION; NONHUMAN; PHYSICAL CHEMISTRY; PROTEIN EXPRESSION; PSYCHOSIS; REVIEW; SCHIZOPHRENIA; SEQUENCE HOMOLOGY; STRUCTURE ACTIVITY RELATION; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; COGNITION; DRUG DESIGN; MEMORY; METABOLISM; PATENT; PROTEIN CONFORMATION;

ANIMALS; ANTIPSYCHOTIC AGENTS; BINDING SITES; COGNITION; DRUG DESIGN; HUMANS; LIGANDS; MEMORY; MOLECULAR STRUCTURE; MUSCARINIC AGONISTS; NOOTROPIC AGENTS; PATENTS AS TOPIC; PROTEIN CONFORMATION; RECEPTOR, MUSCARINIC M1; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84869745196     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2012.731395     Document Type: Review

References (94)

1. Filmore D. It's a GPCR world. Mod Drug Discov 2004;11:727-30
2. Bonner TI. The molecular basis of muscarinic receptor diversity. Trends Neurosci 1989;12:148-51
3. Bonner TI. New subtypes of muscarinic acetylcholine receptors. Trends Pharmacol Sci 1989;suppl:11-15
4. Geula C. Abnormalities of neural circuitry in Alzheimer's disease: Hippocampus and cortical innervation. Neurology 1998;51:S18-29
5. Hansen R, Gartlehner G, Webb AP, et al. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: A systematic review and meta-analysis. Clin Interv Aging 2008;3:211-25
6. Rouse ST, Marino MJ, Potter LT, et al. Muscarinic receptor sub-types involved in hippocampal circuits. Life Sci 1999;64:501-9
7. Anagnostaras SG, Murpht GG, Hamilton SE, et al. Selective cognitive disfunction in acetylcholine M1 muscarinic receptor mutant mice. Nat Neurosci 2003;6:51-8
8. Wess J. Muscarinic acetylcholine receptor knockout mice: Novel phenotypes and clinical implications. Annu Rev Pharmacol Toxicol 2004;44:423-50
9. Langmead CJ, Watson J, Reavill C. Muscarinic acetylcholine receptors as CNS drug targets. Pharmacol. Ther 2008;117:232-43
10. Scarr E, Dean B. Muscarinic receptors: Do they have a role in the pathology and treatment of schizophrenia. J Neurochem 2008;107:1188-95
11. Jones CK, Buyn N, Bubser M. Muscarinic and nicotinic acetylcholine receptor agonists and allosteric modulators for the treatment of schizophrenia. Neuropsychopharmacology 2011;1:1-27
12. Bridges TM, LeBois EP, Hopkins CR, et al. The antipsychotic potential of muscarinic allosteric modulation. Drug News Perspect 2010;23:229-40
13. Sur C, Kinney GG. Selective targeting of muscarinic receptors:novel therapeutic approaches for psychotic disorders. Curr Neuropharmacol 2005;3:63-71
14. Sellin AK, Shad M, Tamminga C. Muscarinic agonists for the treatment of cognition in schizophrenia. CNS Spectr 2008;13:985-96
15. Fisher A. Cholingergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: Perspectives and challenges in treatment of Alzheimer's disease. J Neurochem 2012;120:22-33
16. Greenlee W, Clader J, Asbersom T, et al. Muscarinic agonists and antagonists in the treatment of Alzheimer's disease. Il Farmaco 2001;56:247-50
17. Bodick NC, Offen WW, Levey AI, et al. Effects of Xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavorial symptoms in Alzheimer. Dis Arch Neurol 1997;54:465-73
18. Bymaster FP, Whitesitt CA, Shannon HE. Xanomeline: A selective muscarinic agonist for the treatment of Alzheimer's disease. Drug Dev Res 1997;40:158-70
19. Lieberman JA, Javitch JA, Moore H, et al. Cholinergic agonits as novel treatments for schizophrenia: The promise of rational drug development for pyschiatry. Am J Physchiatry 2008;165:931-6
20. Fisher A. Cholinergic treatments with emphasis on M1 muscarinic agonists as potential disease modifying agents for Alzheimer's disease. Neurotherapeutics 1999;12:197-214
21. Heinrich JN, Butera JA, Carrick T, et al. Pharmacological comparison of muscarinic ligands: Historical versus more recent muscarinic M1 preferring agonists. Eur J Pharmacol 2009;605:53-6
22. Langmead CJ, Christopoulos A. Allosteric agonists of 7TM receptors: Expanding the pharmacological toolbox. Neuropsychopharmacology 2006;27:475-81
23. Digby GJ, Conn PJ, Lindsley CW. Orthosteric- and allosteric-induced ligand-directed trafficking at GPCRs. Curr Opin Drug Disc Dev 2010;13:587-94
24. Kenakin T. Functional selectivity in GPCR modulator screening. Comb Chem High Throughput Screen 2008;11:337-43
25. Conn PJ, Christopoulus A, Lindsley CW. Allosteric modulators of GPCRs: A novel approach for the treatment of CNS disorders. Nat Rev Drug Discov 2009;8:41-54
26. Spalding TA, Trotter C, Skjaerbaek N, et al. Discovery of an ectopic activation site on the M1 muscarinic receptor. Mol Pharmacol 2002;61:1297-302
27. Sur C, Mallorga PJ, Wittmann M, et al. N-desmethylclozapine, an allosteric agonist at muscarinic M1 receptor, potentiates N-methyl-D-aspartate receptor activity. Proc Natl Acad Sci 2003;23:13674-9
28. MaxCyte Corp. Synthesis and Isolation of solid N-desmethylclozapine and crystaline forms thereof. US282200; 2005
29. Bridges TM, Brady AE, Kennedy JP, et al. Synthesis and SAR of analogues of the M1 allosteric agonist. TBPB. Part I: Exploration of alternative benzyl and privileged structure motifs. Bioorg Med Chem Lett 2008;18:5439-42
30. Jones CK, Brady AE, Davis AA, et al. Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats. J Neurosci 2008;41:10422-33
31. Spalding TA, Ma JN, Ott TR, et al. Structural requirements of transmembrane domain 3 for activation by the muscarinic receptor antagonists AC-42, AC-260484, clozapine, and Ndesmethylclozapine: Evidence for three distinct modes of receptor activation. Mol Pharmacol 2006;70:1974-83
32. Langmead CJ, Fry VA, Forbes IT, et al. Proving the molecular mechanism of interaction between AC-42 and the M1 muscarinic receptor: Direct pharmacological evidence that AC-42 is an allosteric agonist. Mol Pharmacol 2006;69:236-46
33. Jacobson MA, Kreatsoulas C, Pascarella DM, et al. The M1 muscarinic receptor allosteric agonists AC-42 and 1-[1'-(2-methylbenzyl)-1,4'-bipiperidin- 4-yl]-13,-dihydro-2H-benzimidazol-2-one bind to a unique site distinct from the acetycholine orthosteric site. Mol Pharmacol 2010;78:648-57
34. Acadia Corp. Compounds with activity on muscarinic receptors. US0144285; 2003
35. Bradley SR, Lameh J, Ohrmund L, et al. AC-260584, an orally bioavailable M1 muscarinic receptor allosteric agonist, improves cognitive performance in an animal model. Neuropharmacology 2010;58:365-73
36. Acadia Corp. Benzimidazolone derivatives as muscarinic agents. US0216840; 2010
37. Acadia Corp. Benzimidazolone derivatives as muscarinic agents. US0205785; 2006
38. Acadia Corp. Muscarinic agonists. US0113357; 2005
39. Lundbeck Corp. Novel heterobicyclic carboxamides as M1 agonists. WO0106534; 2009
40. Sams AG, Hentzer M, Mikkelsen GK, et al. Discovery of N-{1-[3-(3-Oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl] piperidin-4-yl}-2- phenylacetamide (Lu AE51090): An allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. J Med Chem 2010;53:6386-97
41. Lundbeck Corp. Novel piperidinyl-1,3-dihydro-benzoimidazol-2-ones as M1 agonists. WO124882; 2009
42. Lundbeck Corp. Novel 1,3-dihydrobenzoimidazol-2-ones as M1 agonist. WO124883; 2009
43. Marlo JE, Niswender CM, Days EL, et al. Discovery and Characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity. Mol Pharm 2009;75:577-88
44. Vanderbilt University. Amidobipiperidinecarboxylate M1 allosteric agonists, analogs, and derivatives thereof, and methods of making and using same. WO096703; 2010
45. Lebois EP, Digby GJ, Sheffler DJ, et al. Development of a highly selective, orally bioavailable and CNS penetrant M1 agonist derived from the MLPCN probe ML071. Bioorg Med Chem Lett 2011;21:6451-5
46. Vanderbilt University. Alkyl 3-((2-amidoethyl)amino)-8-azabicyclo[3.2.1] octane-8-carboxylate analogs as selective M1 agonists and methods of making and using same. WO087812; 2011
47. Vanderbilt University. Heterocyclylazabicyclo[ 3.2.1]octane analogs as selective M1 agonists and methods of making and using same. WO112825; 2011
48. Conn PJ, Jones CK, Lindsley CW. Subtype-selective allosteric modulators of the muscarinic receptors for the treatment of CNS disorders. Trends Pharmacol Sci 2009;30:148-55
49. Bridges TM, Kennedy JP, Noetzel MJ, et al. Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: Development of a potent and highly selective M1 PAM. Bioorg Med Chem Lett 2010;20:1972-5
50. Vanderbilt University. Indole compounds as positive allosteric modulators of the muscarinic receptor. WO0163280; 2011
51. Reid PR, Bridges TM, Sheffler DJ, et al. Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): The development of ML169, an MLPCN probe. Bioorg Med Chem Lett 2011;21:2697-701
52. Merck & Co. Treatment of psychosis with a muscarinic M1 receptor ectopic activator. WO073639; 2004
53. Merck & Co. Benzyl-substituted quinolone M1 receptor positive allosteric modulators. WO002621; 2008
54. Merck & Co. Benzyl substituted quinolone M1 receptor positive allosteric modulators. WO002621; 2008
55. Ma L, Seager M, Wittmann M, et al. Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation. Proc Natl Acad Sci USA 2009;106:15950-5
56. Merck & Co. Quinolone M1 receptor positive allosteric modulators. TW40814; 2008
57. Merck & Co. Quinolone M1 receptor positive allosteric modulators. WO134668; 2009
58. Merck & Co. N-Heterocyclic M1 receptor positive allosteric modulators. EP2312949; 2008
59. Merck & Co. Fused heterocyclic M1 receptor positive allosteric modulators. EP2355659; 2008
60. Kuduk SD, Di Marco CN, Cofre V, et al. Pyridine containing M1 positive allosteric modulators with reduced plasma protein binding. Bioorg Med Chem Lett 2009;19:657-60
61. Kuduk SD, Di Marco CN, Cofre V, et al. N-heterocyclic derived M1 positive allosteric modulators. Bioorg Med Chem Lett 2010;20:1334-7
62. Kuduk SD, Di Marco CN, Chang RK, et al. Fused heterocyclic M1 positive allosteric modulators. Bioorg Med Chem Lett 2011;20:2769-72
63. Merck & Co. Fused Pyridone M1 receptor positive allosteric modulators. WO102588; 2009
64. Kuduk SD, DiPardo RM, Beshore DC, et al. Hydroxy cycloalkyl fused pyridone carboxylic acid M1 positive allosteric modulators. Bioorg Med Chem Lett 2010;20:2538-41
65. Kuduk SD, Di Marco CN, Chang RK, et al. Heterocyclic Fused Pyridone Carboxylic Acid M1 Positive Allosteric Modulators. Bioorg Med Chem Lett 2010;20:533-2537
66. Merck & Co. Quinolizidinone M1 receptor positive allosteric modulators. WO042347; 2010
67. Merck & Co. Quinolizidinone M1 receptor positive allosteric modulators. US0112077; 2011
68. Kuduk SD, Chang RK, Di Marco CN, et al. Quinolizidinone Carboxylic Acids as CNS Penetrant, Selective M1 Allosteric Muscarinic Receptor Modulators. ACS Med Chem Lett 2010;1:263-7
69. Merck & Co. Quinolizidinone M1 receptor positive allosteric modulators. US046145; 2011
70. Merck & Co. Quinolizidinone M1 receptor positive allosteric modulators. (US or WO117283); 2009
71. Kuduk SD, Chang RK, Di Marco CN, et al. Quinolizidinone carboxylic acid selective M1 allosteric moduators: SAR in the piperidine series. 059773; Bioorg Med Chem Lett 2011;21:1710-15
72. Merck & Co. Quinolizidinone M1 receptor positive allosteric modulators. WO051715; 2009
73. Kuduk SD, Chang RK, Di Marco CN, et al. Discovery of a selective allosteric M1 receptor modulator with suitable development properties based on a quinolizidinone carboxylic acid scaffold. J Med Chem 2011;13:4773-80
74. Merck & Co. Quinolizidinone carboxamide M1 receptor positive allosteric modulators. WO062853; 2011
75. Merck & Co. Naphthalene carboxamide M1 receptor positive allosteric modulators. WO149801; 2011
76. Merck & Co. Aryl methyl benzoquinazoline M1 receptor positive allosteric modulators. WO059773; 2010
77. Merck & Co. Pyranyl aryl methyl benzoquinazoline M1 receptor positive allosteric modulators. WO025851; 2011
78. Merck & Co. Amino benzoquinazoline M1 receptor positive allosteric modulators. WO084371; 2011
79. Merck & Co. Pyridobenzoquinazoline M1 receptor positive allosteric modulators. WO075371; 2011
80. Merck & Co. Isoindolone M1 receptor positive allosteric modulators. WO003147; 2012
81. Merck & Co. Isoindolone M1 receptor positive allosteric modulators. WO096338; 2010
82. Merck & Co. Isoindolone M1 receptor positive allosteric modulators. WO123716; 2010
83. Merck & Co. Isoindolone M1 receptor positive allosteric modulators. WO049731; 2011
84. Langmead CJ, Austin NE, Branch CL, et al. Characterization of a CNS penetrant, selective M1 muscarinic receptor agonist, 77-LH-28-1. Br J Pharm 2008;154:1104-15
85. Budzik B, Garzya V, Shi D, et al. Novel N-substituted benzimidazolones as potent, selective, CNS-penetrant, and orally active M1 mAChR agonists. ACS Med Chem Lett 2010;1:244-8
86. GSK. Compounds which have activity at M1 receptor and their uses in medicine. WO036718; 2007
87. GSK. Benzimidazolones which have activity at M1 receptor and their uses in medicine. WO107567; 2007
88. Huiban M, Pampols-Maso S, Passchier J. Fully automated synthesis of the M1 receptor agonist [11C] GSK1034702 for clinical use on an Eckert & Ziegler Modular Lab system. Appl Radiat Isot 2011;69:1390-4
89. GSK. Compounds which have activity at M1 receptor and their uses in medicine. WO036715; 2007
90. GSK. Benzoimidazolone derivatives which have activity at M1 receptor and their uses in medicine. WO1197712; 2008
91. GSK. 1-(1-Cyclobutyl-4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one derivatives which have activity on the ML receptor and their uses as medicine. WO119720; 2008
92. GSK. 1-(1-Cyclohexyl-4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one derivatives which have activity on the M1 receptor and their uses in medicine. WO119716; 2008
93. Johnson DJ, Forbes IT, Watson SP. The discovery of a series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles as highly brain penetrant, selective muscarinic M1 agonists. Bioorg Med Chem Lett 2010;20:5434-8
94. GSK. Compounds which have activity at the M1 receptor and their uses in medicine. WO037294; 2009