The first structure-activity relationship studies for designer receptors exclusively activated by designer drugs

ACS Chemical Neuroscience

Volumn 6, Issue 3, 2015, Pages 476-484

  Chen, Xin ^a   Choo, Hyunah ^b,c   Huang, Xi Ping ^b   Yang, Xiaobao ^a   Stone, Orrin ^b   Roth, Bryan L ^b   Jin, Jian ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^c Korea Institute of Science and Technology   (South Korea)

Author keywords

CNO; DREADD; hM3Dq; neuronal activation; perlapine; SAR

Indexed keywords

1 (4 (8 CHLORO 5H DIBENZO[B,E][1,4]DIAZEPIN 11 YL)PIPERAZIN 1YL)ETHANONE; 11 (4 ETHYLPIPERAZIN 1 YL) 5H DIBENZO[B,E][1,4]DIAZEPINE; 11 (PIPERAZIN 1 YL) 5H DIBENZO[B,E][1,4]DIAZEPINE; 4 (5H DIBENZO[B,E][1,4]DIAZEPIN 11 YL) 1 ETHYLPIPERAZINE N OXIDE; 4 (8 CHLORO 5H DIBENZO[B,E][1,4]DIAZEPIN 11 YL) 1 ETHYLPIPERAZINE N OXIDE; 4 (8 CHLORO 5H DIBENZO[B,E][1,4]DIAZEPIN 11 YL) 1 ISOPROPYLPIPERAZINE N OXIDE; 4 (8 CHLORO 5H DIBENZO[B,E][1,4]DIAZEPIN 11 YL) 1 PROPYLPIPERAZINE N OXIDE; 4 (8 CHLORO 5H DIBENZO[B,E][1,4]DIAZEPIN 11 YL) 1,1 DIMETHYLPIPERAZIN 1 IUM IODIDE; 4 (8 CHLORO 5H DIBENZO[B,E][1,4]DIAZEPIN 11 YL) 1,3,8 TRIAZASPIRO[4,5]DECANE 2,4 DIONE; 4 (8 CHLORO 5H DIBENZO[B,E][1,4]DIAZEPIN 11 YL)PIPERAZIN 2 ONE; 4 AMINO 1 (8 CHLORO 5H DIBENZO[B,E][1,4]DIAZEPIN 11 YL)PIPERIDINE 4 CARBOXYLIC ACID; 8 CHLORO 11 (4 (METHYLSULFONYL)PIPERAZIN 1 YL] 5H DIBENZO[B,E][1,4]DIAZEPINE; 8 CHLORO 11 (4 ISOPROPYLPIPERAZIN 1 YL) 5H DIBENZO[B,E][1,4]DIAZEPINE; 8 CHLORO 11 (4 PROPYLPIPERAZIN 1 YL) 5H DIBENZO[B,E][1,4]DIAZEPINE; 8 CHLORO 11 [4 (1,1 DIDEUTRIOETHYL)PIPERAZIN 1 YL] 5H DIBENZO[B,E][1,4]DIAZEPINE; CLOZAPINE N OXIDE; DESIGNER RECEPTORS EXCLUSIVELY ACTIVATED BY DESIGNER DRUG; G PROTEIN COUPLED RECEPTOR; PERLAPINE; UNCLASSIFIED DRUG; ACETYLCHOLINE; CHOLINERGIC RECEPTOR STIMULATING AGENT; CLOZAPINE; CLOZAPINE N-OXIDE; DESIGNER DRUG; DIBENZAZEPINE DERIVATIVE; LIGAND; MUSCARINIC M3 RECEPTOR; SEROTONIN ANTAGONIST;

ARTICLE; DRUG DESIGN; DRUG SYNTHESIS; EC50; GUINEA PIG; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; ANALOGS AND DERIVATIVES; ANIMAL; CHEMISTRY; DRUG EFFECTS; SIGNAL TRANSDUCTION;

CAVIA; MUS; RODENTIA;

ACETYLCHOLINE; ANIMALS; CHOLINERGIC AGONISTS; CLOZAPINE; DESIGNER DRUGS; DIBENZAZEPINES; HUMANS; LIGANDS; RECEPTOR, MUSCARINIC M3; SEROTONIN ANTAGONISTS; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84925136303     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn500325v     Document Type: Article

References (51)

1. Sternson, S. M. and Roth, B. L. (2014) Chemogenetic Tools to Interrogate Brain Functions Annu. Rev. Neurosci. 37, 387-407
2. Urban, D. J. and Roth, B. L. (2015) DREADDs (Designer Receptors Exclusively Activated by Designer Drugs): Chemogenetic Tools with Therapeutic Utility Annu. Rev. Pharmacol. Toxicol. 55, 399-417
3. Penfield, W. and Jasper, H. H. (1954) Epilepsy and the Functional Anatomy of the Human Brain (First ed.), Little Brown, Boston.
4. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., and Deisseroth, K. (2005) Millisecond-timescale, genetically targeted optical control of neural activity Nat. Neurosci. 8, 1263-1268
5. Armbruster, B. N. and Roth, B. L. (2005) Mining the receptorome J. Biol. Chem. 280, 5129-5132
6. Zhang, F., Wang, L. P., Brauner, M., Liewald, J. F., Kay, K., Watzke, N., Wood, P. G., Bamberg, E., Nagel, G., Gottschalk, A., and Deisseroth, K. (2007) Multimodal fast optical interrogation of neural circuitry Nature 446, 633-639
7. Airan, R. D., Thompson, K. R., Fenno, L. E., Bernstein, H., and Deisseroth, K. (2009) Temporally precise in vivo control of intracellular signalling Nature 458, 1025-1029
8. Berndt, A., Yizhar, O., Gunaydin, L. A., Hegemann, P., and Deisseroth, K. (2009) Bi-stable neural state switches Nat. Neurosci. 12, 229-234
9. Li, X., Gutierrez, D. V., Hanson, M. G., Han, J., Mark, M. D., Chiel, H., Hegemann, P., Landmesser, L. T., and Herlitze, S. (2005) Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin Proc. Natl. Acad. Sci. U. S. A. 102, 17816-17821
10. Zhang, F., Prigge, M., Beyriere, F., Tsunoda, S. P., Mattis, J., Yizhar, O., Hegemann, P., and Deisseroth, K. (2008) Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri Nat. Neurosci. 11, 631-633
11. Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S., and Roth, B. L. (2007) Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand Proc. Natl. Acad. Sci. U. S. A. 104, 5163-5168
12. Alexander, G. M., Rogan, S. C., Abbas, A. I., Armbruster, B. N., Pei, Y., Allen, J. A., Nonneman, R. J., Hartmann, J., Moy, S. S., Nicolelis, M. A., McNamara, J. O., and Roth, B. L. (2009) Remote Control of Neuronal Activity in Transgenic Mice Expressing Evolved G Protein-Coupled Receptors Neuron 63, 27-39
13. Rogan, S. C. and Roth, B. L. (2011) Remote control of neuronal signaling Pharmacol. Rev. 63, 291-315
14. Farrell, M. S. and Roth, B. L. (2012) Pharmacosynthetics: Reimagining the pharmacogenetic approach Brain Res. 1511, 6-20
15. Jennings, J. H. and Stuber, G. D. (2014) Tools for Resolving Functional Activity and Connectivity within Intact Neural Circuits Curr. Biol. 24, R41-50
16. Lee, H. M., Giguere, P. M., and Roth, B. L. (2013) DREADDs: Novel tools for drug discovery and development Drug Discovery Today 19, 469-473
17. Giguere, P. M., Kroeze, W. K., and Roth, B. L. (2014) Tuning up the right signal: Chemical and genetic approaches to study GPCR functions Curr. Opin. Cell Biol. 27, 51-55
18. Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S., and Roth, B. L. (2007) Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand Proc. Natl. Acad. Sci. U. S. A. 104, 5163-5168
19. Ray, R. S., Corcoran, A. E., Brust, R. D., Kim, J. C., Richerson, G. B., Nattie, E., and Dymecki, S. M. (2011) Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition Science 333, 637-642
20. Garner, A. R., Rowland, D. C., Hwang, S. Y., Baumgaertel, K., Roth, B. L., Kentros, C., and Mayford, M. (2012) Generation of a synthetic memory trace Science 335, 1513-1516
21. Atasoy, D., Betley, J. N., Su, H. H., and Sternson, S. M. (2012) Deconstruction of a neural circuit for hunger Nature 488, 172-177
22. Krashes, M. J., Shah, B. P., Madara, J. C., Olson, D. P., Strochlic, D. E., Garfield, A. S., Vong, L., Pei, H., Watabe-Uchida, M., Uchida, N., Liberles, S. D., and Lowell, B. B. (2014) An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger Nature 507, 238-242
23. Kuhlman, S. J., Olivas, N. D., Tring, E., Ikrar, T., Xu, X., and Trachtenberg, J. T. (2013) A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex Nature 501, 543-546
24. Carter, M. E., Soden, M. E., Zweifel, L. S., and Palmiter, R. D. (2013) Genetic identification of a neural circuit that suppresses appetite Nature 503, 111-114
25. Vrontou, S., Wong, A. M., Rau, K. K., Koerber, H. R., and Anderson, D. J. (2013) Genetic identification of C fibres that detect massage-like stroking of hairy skin in vivo Nature 493, 669-673
26. Kozorovitskiy, Y., Saunders, A., Johnson, C. A., Lowell, B. B., and Sabatini, B. L. (2012) Recurrent network activity drives striatal synaptogenesis Nature 485, 646-650
27. Ferguson, S. M., Eskenazi, D., Ishikawa, M., Wanat, M. J., Phillips, P. E., Dong, Y., Roth, B. L., and Neumaier, J. F. (2011) Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization Nat. Neurosci. 14, 22-24
28. Silva, B. A., Mattucci, C., Krzywkowski, P., Murana, E., Illarionova, A., Grinevich, V., Canteras, N. S., Ragozzino, D., and Gross, C. T. (2013) Independent hypothalamic circuits for social and predator fear Nat. Neurosci. 16, 1731-1733
29. Bock, R., Shin, J. H., Kaplan, A. R., Dobi, A., Markey, E., Kramer, P. F., Gremel, C. M., Christensen, C. H., Adrover, M. F., and Alvarez, V. A. (2013) Strengthening the accumbal indirect pathway promotes resilience to compulsive cocaine use Nat. Neurosci. 16, 632-638
30. Parnaudeau, S., ONeill, P. K., Bolkan, S. S., Ward, R. D., Abbas, A. I., Roth, B. L., Balsam, P. D., Gordon, J. A., and Kellendonk, C. (2013) Inhibition of mediodorsal thalamus disrupts thalamofrontal connectivity and cognition Neuron 77, 1151-1162
31. 2+ axis controls circuit-level encoding of circadian time in the suprachiasmatic nucleus Neuron 78, 714-728
32. Kong, D., Tong, Q., Ye, C., Koda, S., Fuller, P. M., Krashes, M. J., Vong, L., Ray, R. S., Olson, D. P., and Lowell, B. B. (2012) GABAergic RIP-Cre neurons in the arcuate nucleus selectively regulate energy expenditure Cell 151, 645-657
33. Bender, D., Holschbach, M., and Stocklin, G. (1994) Synthesis of n.c.a. carbon-11 labelled clozapine and its major metabolite clozapine-N-oxide and comparison of their biodistribution in mice Nucl. Med. Biol. 21, 921-925
34. Chang, W. H., Lin, S. K., Lane, H. Y., Wei, F. C., Hu, W. H., Lam, Y. W. F., and Jann, M. W. (1998) Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients Prog. Neuro-Psychopharmacol. 22, 723-739
35. Massey, C. A., Kim, G., Corcoran, A. E., Haynes, R. L., Paterson, D. S., Cummings, K. J., Dymecki, S. M., Richerson, G. B., Nattie, E. E., Kinney, H. C., and Commons, K. G. (2013) Development of brainstem 5HT(1A) receptor-binding sites in serotonin-deficient mice J. Neurochem. 126, 749-757
36. Jann, M. W., Lam, Y. W., and Chang, W. H. (1994) Rapid formation of clozapine in guinea-pigs and man following clozapine-N-oxide administration Arch. Int. Pharmacodyn. Ther. 328, 243-250
37. Loffler, S., Korber, J., Nubbemeyer, U., and Fehsel, K. (2012) Comment on Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition Science 337, 646
38. Roth, B. L., Sheffler, D. J., and Kroeze, W. K. (2004) Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia Nat. Rev. Drug Discovery 3, 353-359
39. Hunziker, F., Kuenzle, F., and Schmutz, J. (1966) Helv. Chim. Acta 49, 1433-1439
40. Schmutz, J. (1975) Neuroleptic piperazinyl-dibenzo-azepines. Chemistry and structure-activity relationships Arzneimittelforschung 25, 712-720
41. Steiner, G., Franke, A., Hadicke, E., Lenke, D., Teschendorf, H. J., Hofmann, H. P., Kreiskott, H., and Worstmann, W. (1986) Tricyclic epines. Novel (E)- and (Z)-11 H -dibenz[ b, e ]azepines as potential central nervous system agents. Variation of the basic side chain J. Med. Chem. 29, 1877-1888
42. Hunziker, F., Fischer, E., and Schmutz, J. (1967) 11-Amino-5 H -Dibenzo[ b, e ]-1,4-diazepine 0.10. Mitteilung Uber Siebengliedrige Heterocyclen Helv. Chim. Acta 50, 1588-1599
43. Wenthur, C. J. and Lindsley, C. W. (2013) Classics in Chemical Neuroscience: Clozapine ACS Chem. Neurosci. 4, 1018-1025
44. Kalhapure, R. S., Patil, B. P., Jadhav, M. N., Kawle, L. A., and Wagh, S. B. (2011) Synthesis of 11-(Piperazin-1-yl)-5 H -dibenzo[ b, e ] [1,4]diazepine on Kilo Scale E-J. Chem. 8, 1747-1749
45. Ullmann, F. and Bielecki, J. (1901) Synthesis in the Biphenyl series. (I. Announcement) Ber. Dtsch. Chem. Ges. 34, 2174-2185
46. Davies, M. A., Compton-Toth, B. A., Hufeisen, S. J., Meltzer, H. Y., and Roth, B. L. (2005) The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M1 agonism a pre-requisite for mimicking clozapines actions? Psychopharmacology 178, 451-460
47. Besnard, J., Ruda, G. F., Setola, V., Abecassis, K., Rodriguiz, R. M., Huang, X. P., Norval, S., Sassano, M. F., Shin, A. I., Webster, L. A., Simeons, F. R., Stojanovski, L., Prat, A., Seidah, N. G., Constam, D. B., Bickerton, G. R., Read, K. D., Wetsel, W. C., Gilbert, I. H., Roth, B. L., and Hopkins, A. L. (2012) Automated design of ligands to polypharmacological profiles Nature 492, 215-220
48. Wiberg, K. B. (1955) The Deuterium Isotope Effect Chem. Rev. 55, 713-743
49. 3 Group on Potency and Enzymatic N-Demethylation of Morphine Science 134, 1078-1079
50. Shao, L., Abolin, C., Hewitt, M. C., Koch, P., and Varney, M. (2006) Derivatives of tramadol for increased duration of effect Bioorg. Med. Chem. Lett. 16, 691-694
51. Korber, J., Loffler, S., Schollmeyer, D., and Nubbemeyer, U. (2013) Synthesis and Oxidant Properties of Phase 1 Benzepine N-Oxides of Common Antipsychotic Drugs Synthesis 45, 2875-2887