Journal of Medicinal Chemistry
Page 6 of 16
anxiety in metabotropic glutamate receptor 7-deficient
isoxazolopyridone derivatives as allosteric metabotropic
1
2
3
4
5
6
7
8
mice. J. Neurosci. 2006, 26, 6573-6582.
glutamate receptor 7 antagonists. J. Pharmacol. Exp. Ther.
2007, 323, 147–156.
(17) Nakamura, M.; Kurihara, H.; Suzuki, G.; Mitsuya, M.;
Ohkubo, M.; Ohta, H. Isoxazolopyridone derivatives as
allosteric metabotropic glutamate receptor 7 antagonists.
Bioorg. Med. Chem. Lett. 2010, 20, 726–729.
(8) Mitsukawa, K.; Mombereau, C.; Lötscher, E.; Uzunov,
D.P.; van der Putten, H.; Flor, P.J.; Cryan, J.F.
Metabotropic glutamate receptor subtype 7 ablation causes
dysregulation of the HPA axis and increases hippocampal
BDNF protein levels: implications for stress-related
psychiatric disorders. Neuropsychopharmacology 2006,
31, 1112-1122.
(9) Hölscher, C.; Schmid, S.; Pilz, P.K.; Sansig, G.; van der
Putten, H.; Plappert, C.F. Lack of the metabotropic
glutamate receptor subtype 7 selectively modulates Theta
rhythm and working memory. Learn. Mem 2005, 12, 450-
455.
(10) Hölscher, C.; Schmid, S.; Pilz, P.K.; Sansig, G.; van der
Putten, H.; Plappert, C.F. Lack of the metabotropic
glutamate receptor subtype 7 selectively impairs short-term
working memory but not long-term memory. Behav. Brain
Res. 2004, 154, 473-481.
(11) Bushell, T.J.; Sansig, G.; Collett, V.J.; van der Putten, H.;
Collingridge, G.L. Altered short-term synaptic plasticity in
mice lacking the metabotropic glutamate receptor mGlu7.
ScientificWorldJournal 2002, 2, 730-737.
(12) Masugi, M.; Yokoi, M.; Shigemoto, R.; Muguruma, K.;
Watanabe, Y.; Sansig, G.; van der Putten, H.; Nakanishi, S.
Metabotropic glutamate receptor subtype 7 ablation causes
deficit in fear response and conditioned taste aversion. J.
Neurosci. 1999, 19, 955-963.
(13) Gogliotti R.G.; Senter R.K.; Fisher N;, Adams J.;
Zamorano R.; Walker A.G.; Blobaum A.L.; Engers D.W.;
Hopkins C.R.; Daniels J.S.; Jones, C.K.; Lindsley C.W.;
Xiang Z.; Conn P.J.; and Niswender C.M.. mGlu7
potentiation rescues cognitive, social, and respiratory
phenotypes in a mouse model of Rett syndrome. Sci. Trans.
Med. 2017, 9, eaai7459.
(14) Jalan-Sakrikar, N.; Field, J.R.; Klar, R.; Mattmann, M.E.;
Gregory, K.J.; Zamorano, R.; Engers, D.W.; Bollinger,
S.R.; Weaver, C.D.; Days, E.L.; Lewis, L.M.; Utley, T.J.;
Hurtado, M.; Rigault, D.; Acher, F.; Walker, A.G.;
Melancon, B.J.; Wood, M.R.; Lindsley, C.W.; Conn, P.J.;
Xiang, Z.; Hopkins, C.R.; Niswender, C.M. Identification
of positive allosteric modulators VU0155094 (ML397) and
VU0422288 (ML396) reveals new insights into the biology
of metabotropic glutamate receptor 7. ACS Chem.
Neurosci. 2014, 5, 1221-1237.
(15) Abe, M.; Seto, M.; Gogliotti, R.G.; Loch, M.T.; Bollinger,
K.A.; Chang, S.; Engelberg, E.M.; Luscombe, V.B.; Harp,
J.M.; Bubser, M.; Engers, D.W.; Jones, C.K.; Rodriguez,
A.L.; Blobaum, A.L.; Conn, P.J.; Niswender, C.M.;
Lindsley, C.W. Discovery of VU6005649, a CNS penetrant
(18) Kalinichev, M.; Rouillier, M.; Girard, F.; Royer-Urios, I.;
Bournique, B.; Finn, T.; Charvin, D.; Campo, B.; Le Poul,
E.; Mutel, V.; Poli, S.; Neale, S.A.; Salt, T.E.; Lutjens, R.
ADX71743, a potent and selective negative allosteric
modulator of metabotropic glutamate receptor 7: in vitro
and in vivo characterization. J. Pharmacol. Exp. Ther.
2013, 344, 624-636.
(19) Gee, C.E.; Peterlik, D.; Neuhäuser, C.; Bouhelal, R.;
Kaupmann, K.; Laue, G.; Uschold-Schmidt, N.;
Feuerbach, D.; Zimmermann, K.; Ofner, S.; Cryan, J.F.;
van der Putten, H.; Fendt, M.; Vranesic, I.; Glatthar, R.;
Flor, P.J. Blocking metabotropic glutamate receptor
subtype 7 (mGlu7) via the Venus fly trap domain (VFTD)
inhibits amygdala plasticity, stress, and anxiety-related
behaviors. J. Biol. Chem. 2014, 289, 10975-10987.
(20) Niswender, C.M.; Johnson, K.A.; Miller, N.R.; Ayala, J.E.;
Luo, Q.; Williams, R.; Saleh, S.; Orton, D.; Weaver, C.D.;
Conn, P.J. Context-dependent pharmacology exhibited by
negative allosteric modulators of metabotropic glutamate
receptor 7. Mol. Pharmacol. 2010, 77, 459–468.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(21) Reed, C.W.; McGowan, K.M.; Spearing, P.K.; Stansley,
B.J.; Roenfanz, H.F.; Engers, D.W.; Rodriguez, A.L.;
Engelberg, E.M.; Luscombe, V.B.; Loch, M.T.; Remke
D.H.; Rook, J.M.; Blobaum, A.L.; Conn, P.J.; Niswender,
C.M.; Lindsley, C.W. VU6010608, a novel mGlu7 NAM
from
a
series of N-(2-(1H-1,2,4-triazol-1-yl)-5-
(trifluoromethoxy)phenyl)benzamides. ACS Med. Chem.
Lett. 2017, 8, 1326-1330.
(22) See Supporting Information for full experimental details.
Grannan, M.; Noetzel, M.J.; Lamsal, A.; Niswender, C.M.;
Daniels, J.S.; Poslusney, M.S.; Melancon, B.J.; Tarr, J.C.;
Byers, F.W.; Wess, J.; Duggan, M.E.; Dunlop, J.; Wood,
P.J.; Jones C.K. Selective activation of M4 muscarinic
acetylcholine receptors reverses MK-801-induced
behavioral impairments and enhances associative learning
in rodents. ACS Chem. Neurosci. 2014, 5, 920-942.
(24) Engers, D.W.; Blobaum, A.L.; Gogliotti, R.D.; Cheung, Y-
Y.; Salovich, J.M.; Garcia-Barrantes, P.M.; Daniels, J.S.;
Morrison, R.; Jones, C.K.; Soars, M.G.; Zhuo, X.; Hurley,
J.; Macor, J.E.; Bronson, J.J.; Conn, P.J.; Lindsley, C.W.;
Niswender, C.M.; Hopkins, C.R. Discovery, synthesis and
mGlu7/8 receptor PAM derived from
pyrazolo[1,5-a]pyrimidines. ACS Med. Chem. Lett. 2017,
8, 1110-1115.
a series of
preclinical
characterization
of
N-(3-chloro-4-
fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine
(VU0418506), a novel positive allosteric modulator of the
metabotropic glutamate receptor 4 (mGlu4). ACS Chem.
Neurosci. 2016, 7, 1192-1200.
(16) Suzuki, G; Tsukamoto, N; Fushiki, H.; Kawagishi, A.;
Nakamura, M.; Kurihara, H.; Mitsuya, M.; Ohkubo, M.;
Ohta, H. In vitro pharmacological characterization of novel
ACS Paragon Plus Environment