Conformationally restricted GABA with bicyclo[3.1.0]hexane backbone as the first highly selective BGT-1 inhibitor

ACS Medicinal Chemistry Letters

Volumn 5, Issue 8, 2014, Pages 889-893

  Kobayashi, Takaaki ^a   Suemasa, Akihiro ^a   Igawa, Arisa ^a   Ide, Soichiro ^a   Fukuda, Hayato ^a   Abe, Hiroshi ^a   Arisawa, Mitsuhiro ^a,b   Minami, Masabumi ^a   Shuto, Satoshi ^a  

^a HOKKAIDO UNIVERSITY   (Japan)

^b OSAKA UNIVERSITY   (Japan)

Author keywords

BGT 1; conformational restriction; cyclopropane; GABA; GAT

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID UPTAKE INHIBITOR; BICYCLO[3.1.0]HEXANE DERIVATIVE; CYCLOPROPANE; UNCLASSIFIED DRUG;

4 AMINOBUTYRIC ACID UPTAKE; ARTICLE; CONFORMATION; DENSITY FUNCTIONAL THEORY; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; IC 50; NONHUMAN; PRIORITY JOURNAL; STEREOISOMERISM;

EID: 84906282999     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml500134k     Document Type: Article

References (30)

1. Schousboe, A.; Sarup, A.; Larsson, O. M.; White, H. S. GABA transporters as drug targets for modulation of GABAergic activity Biochem. Pharmacol. 2004, 68, 1557-1563
2. Galvan, A.; Kuwajima, M.; Smith, Y. Glutamate and GABA receptors and transporters in the basal ganglia: What does their subsynaptic localization reveal about their function? Neuroscience 2006, 143, 351-375
3. Jin, X.-T.; Paré, J.-F.; Smith, Y. Differential localization and function of GABA transporters, GAT-1 and GAT-3, in the rat globus pallidus Eur. J. Neurosci. 2011, 33, 1504-1518
4. Madsen, K. K.; White, H. S.; Schousboe, A. Neuronal and non-neuronal GABA trasporters as targets for antiepileptic drugs Pharmacol. Ther. 2010, 125, 394-401
5. Soudijn, W.; Wijngaarden, I. V. The GABA transporter and its inhibitors Curr. Med. Chem. 2000, 7, 1063-1079
6. Dalby, N. O. Inhibition of γ-aminobutyric acid uptake: anatomy, physiology and effects against epileptic seizures Eur. J. Pharmacol. 2003, 479, 127-137
7. Høg, S.; Greenwood, J. R.; Madsen, K. B.; Larsson, O. M.; Frølund, B.; Schousboe, A.; Krogsgaard-Larsen, P.; Clausen, R. P. Structure-activity relationships of selective GABA uptake inhibitors Curr. Top. Med. Chem. 2006, 6, 1861-1882
8. Borden, L. A. GABA transporter heterogeneity: pharmacology and cellular localization Neurochem. Int. 1996, 29, 335-356
9. Andersen, K. E.; Braestrup, C.; Grønwald, F. C.; Jørgensen, A. S.; Nielsen, E. B.; Sonnewald, U.; Sørensen, P. O.; Suzdak, P. D.; Knutsen, L. J. The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl- 2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidate J. Med. Chem. 1993, 36, 1716-1725
10. Suzdak, P. D.; Jansen, J. A. A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor Epilepsia 1995, 36, 612-626
11. Clausen, R. P.; Moltzen, E. K.; Perregaard, J.; Lenz, S. M.; Sanchez, C.; Falch, E.; Frolund, B.; Bolvig, T.; Sarup, A.; Larsson, O. M.; Schousboe, A.; Krogsgaard-Larsen, P. Selective inhibitors of GABA uptake: synthesis and molecular pharmacology of 4- N -methylamino-4,5,6,7-tetrahydrobenzo[ d ]isoxazol-3-ol analogues Bioorg. Med. Chem. 2005, 13, 895-908
12. Clausen, R. P.; Frolund, B.; Larsson, O. M.; Schousboe, A.; Krogsgaard-Larsen, P.; White, H. S. A novel selective gamma-aminobutyric acid transport inhibitor demonstrates a functional role for GABA transporter subtype GAT2/BGT-1 in the CNS Neurochem. Int. 2006, 48, 637-42
13. White, H. S.; Watson, W. P.; Hansen, S. L.; Slough, S.; Perregaard, J.; Sarup, A.; Bolvig, T.; Petersen, G.; Larsson, O. M.; Clausen, R. P.; Frolund, B.; Falch, E.; Krogsgaard-Larsen, P.; Schousboe, A. First demonstration of a functional role for central nervous system betaine/{gamma}-aminobutyric acid transporter (mGAT2) based on synergistic anticonvulsant action among inhibitors of mGAT1 and mGAT2 J. Pharmacol. Exp. Ther. 2005, 312, 866-74
14. Dalby, N. O.; Thomsen, C.; Fink-Jensen, A.; Lundbeck, J.; Søkilde, B.; Man, C. M.; Sørensen, P. O.; Meldrum, B. Anticonvulsant properties of two GABA uptake inhibitors NNC 05-2045 and NNC 05-2090, not acting preferentially on GAT-1 Epilepsy Res. 1997, 28, 51-61
15. Thomsen, C.; Sørensen, P. O.; Egebjerg, J. 1-(3-(9 H -Carbazol-9-yl)-1-propyl)-4-(2-methoxyphenyl)-4-piperidinol a novel subtype selective inhibitor of the mouse type II GABA-transporter Br. J. Pharmacol. 1997, 120, 983-985
16. Vogensen, S. B.; Jørgensen, L.; Madsen, K. K.; Borkar, N.; Wellendorph, P.; Skovgaard-Petersen, J.; Schousboe, A.; White, H. S.; Krogsgaard-Larsen, P.; Clausen, R. P. Selective mGAT2 (BGT-1) GABA uptake inhibitors: Design, synthesis, and pharmacological characterization J. Med. Chem. 2013, 56, 2160-2164
17. Kazuta, Y.; Matsuda, A.; Shuto, S. Development of versatile cis- and trans- dicarbon-substituted chiral cyclopropane units: synthesis of (1 S,2 R)- and (1 R,2 R)-2-aminomethyl-1-(1 H -imidazol-4-yl)cyclopropanes and their enantiomers as conformationally restricted analogs of histamine J. Org. Chem. 2002, 67, 1669-1677
18. 3 receptor antagonists by the cyclopropylic strain-based conformational restriction strategy J. Med. Chem. 2010, 53, 3585-3593 and references cited therein
19. Nakada, K.; Yoshikawa, M.; Ide, S.; Suemasa, A.; Kawamura, S.; Kobayashi, T.; Masuda, E.; Ito, Y.; Hayakawa, W.; Katayama, T.; Yamada, S.; Arisawa, M.; Minami, M.; Shuto, S. Cyclopropane-based conformational restriction of GABA by a stereochemical diversity-oriented strategy: Identification of an efficient lead for potent inhibitors of GABA transports Bioorg. Med. Chem. 2013, 21, 4938-4950
20. Morikawa, T.; Sasaki, H.; Hanai, R.; Shibuya, A.; Taguchi, T. Synthesis of optically active cis-and trans -1,2-disubstituted cyclopropane derivatives by the Simmons-Smith reaction of allyl alcohol derivatives derived from (R)-2,3- O -isopropylideneglyceraldehyde J. Org. Chem. 1994, 59, 97-103
21. Duke, R. K.; Allan, R. D.; Chebib, M.; Greenwood, J. R.; Johnston, G. A. R. Resolution and conformational analysis of diastereoisomeric esters of cis-and trans -2-(aminomethyl)-1-carboxycyclopropanes Tetrahedron: Asymmetry 1998, 9, 2533
22. Soria, V. R.; Quintero, L.; Piscil, F. S. A novel stereoselective tin-free radical protocol for the enantioselective synthesis of pyrrolidinones and its application to the synthesis of biologically active GABA-derivatives Tetrahedron 2008, 64, 2750-2754
23. Aitken, D. J.; Bull, S. D.; Davies, I. R.; Drouin, L.; Ollivier, J.; Peed, J. An expedient asymmetric synthesis of N-protected (S, S)-2-aminomethyl-1-cyclopropanecarboxylic acid Synlett 2010, 18, 2729-2732
24. Aitken, D. J.; Drouin, L.; Goretta, S.; Guillot, R.; Ollivier, J.; Spiga, M. Stereoselective preparation of β,γ-methano-GABA derivatives Org. Biomol. Chem. 2011, 9, 7517-7524
25. Levandovskiy, I. A.; Sharapa, D. I.; Shamota, T. V.; Rodionov, V. N.; Shubina, T. E. Conformationally restricted GABA analogs: from rigid carbocycles to cage hydrocarbons Future Med. Chem. 2011, 3, 223-241
26. Gajcy, K.; Lochyński, S.; Librowski, T. A role of GABA analogues in the treatment of neurological diseases Curr. Med. Chem. 2010, 17, 2338-2347
27. Kawamura, S.; Unno, Y.; Tanaka, M.; Sasaki, T.; Yamano, A.; Hirokawa, T.; Kameda, T.; Asai, A.; Arisawa, M.; Shuto, S. Investigation of the non-covalent binding mode of covalent proteasome inhibitors around the transition state by combined use of cyclopropylic strain-based conformational restriction and computational modeling J. Med. Chem. 2013, 56, 5829-5842 and references cited therein
28. Ark, A.-Y.; Moon, H. R.; Kim, K. R.; Chun, M. W.; Jeong, L. S. Synthesis of novel l-N -MCd4T as a potent anti-HIV agent Org. Biomol. Chem. 2006, 4, 4065-4067
29. Singh, G. S.; Mollet, K.; D'hooghe, M.; De Kimpe, N. Ephilalohydrins in organic synthesis Chem. Rev. 2013, 113, 1441-1498
30. Similar determination of configuration in a bicyclo[3.1.0]hexanes ring system, see: Shuto, S.; Ono, S.; Hase, Y.; Kamiyama, N.; Takada, H.; Yamashita, K.; Matsuda, A. Conformational restriction by repulsion between adjacent substituents on a cyclopropane ring: Design and enantioselective synthesis of 1-phenyl-2-(1-aminoalkyl)cyclopropane- N, N -diethylcarboxamides as potent NMDA receptor antagonists J. Org. Chem. 1996, 61, 915-923