Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTN9D8E)

• DTT Name: Glutamate receptor ionotropic NMDA 2B (NMDAR2B)
• Synonyms: NR3; NR2B; NMDA receptor subunit 2B; NMDA receptor NR2B; NMDA NR2B receptor; N-methylD-aspartate receptor subtype 2B; N-methyl-D-aspartate receptor subunit 3; N-methyl D-aspartate receptor subtype 2B; HNR3; Glutamate receptor ionotropic, NMDA 2B; Glutamate receptor NR2B subunit; Glutamate [NMDA] receptor subunit epsilon-2; GluN2B
• Gene Name: GRIN2B
• DTT Type: Successful target; [1]
• BioChemical Class: Glutamate-gated ion channel
• UniProt ID: NMDE2_HUMAN
• TTD ID: T76414
• Sequence:
  MKPRAECCSPKFWLVLAVLAVSGSRARSQKSPPSIGIAVILVGTSDEVAIKDAHEKDDFH
  HLSVVPRVELVAMNETDPKSIITRICDLMSDRKIQGVVFADDTDQEAIAQILDFISAQTL
  TPILGIHGGSSMIMADKDESSMFFQFGPSIEQQASVMLNIMEEYDWYIFSIVTTYFPGYQ
  DFVNKIRSTIENSFVGWELEEVLLLDMSLDDGDSKIQNQLKKLQSPIILLYCTKEEATYI
  FEVANSVGLTGYGYTWIVPSLVAGDTDTVPAEFPTGLISVSYDEWDYGLPARVRDGIAII
  TTAASDMLSEHSFIPEPKSSCYNTHEKRIYQSNMLNRYLINVTFEGRNLSFSEDGYQMHP
  KLVIILLNKERKWERVGKWKDKSLQMKYYVWPRMCPETEEQEDDHLSIVTLEEAPFVIVE
  SVDPLSGTCMRNTVPCQKRIVTENKTDEEPGYIKKCCKGFCIDILKKISKSVKFTYDLYL
  VTNGKHGKKINGTWNGMIGEVVMKRAYMAVGSLTINEERSEVVDFSVPFIETGISVMVSR
  SNGTVSPSAFLEPFSADVWVMMFVMLLIVSAVAVFVFEYFSPVGYNRCLADGREPGGPSF
  TIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVWAFFAVIFLASYTANLAAFMIQEEYV
  DQVSGLSDKKFQRPNDFSPPFRFGTVPNGSTERNIRNNYAEMHAYMGKFNQRGVDDALLS
  LKTGKLDAFIYDAAVLNYMAGRDEGCKLVTIGSGKVFASTGYGIAIQKDSGWKRQVDLAI
  LQLFGDGEMEELEALWLTGICHNEKNEVMSSQLDIDNMAGVFYMLGAAMALSLITFICEH
  LFYWQFRHCFMGVCSGKPGMVFSISRGIYSCIHGVAIEERQSVMNSPTATMNNTHSNILR
  LLRTAKNMANLSGVNGSPQSALDFIRRESSVYDISEHRRSFTHSDCKSYNNPPCEENLFS
  DYISEVERTFGNLQLKDSNVYQDHYHHHHRPHSIGSASSIDGLYDCDNPPFTTQSRSISK
  KPLDIGLPSSKHSQLSDLYGKFSFKSDRYSGHDDLIRSDVSDISTHTVTYGNIEGNAAKR
  RKQQYKDSLKKRPASAKSRREFDEIELAYRRRPPRSPDHKRYFRDKEGLRDFYLDQFRTK
  ENSPHWEHVDLTDIYKERSDDFKRDSVSGGGPCTNRSHIKHGTGDKHGVVSGVPAPWEKN
  LTNVEWEDRSGGNFCRSCPSKLHNYSTTVTGQNSGRQACIRCEACKKAGNLYDISEDNSL
  QELDQPAAPVAVTSNASTTKYPQSPTNSKAQKKNRNKLRRQHSYDTFVDLQKEEAALAPR
  SVSLKDKGRFMDGSPYAHMFEMSAGESTFANNKSSVPTAGHHHHNNPGGGYMLSKSLYPD
  RVTQNPFIPTFGDDQCLLHGSKSYFFRQPTVAGASKARPDFRALVTNKPVVSALHGAVPA
  RFQKDICIGNQSNPCVPNNKNPRAFNGSSNGHVYEKLSSIESDV
• Function: Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death. Contributes to neural pattern formation in the developing brain. Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity. Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Circadian entrainment (hsa04713)
  Long-term potentiation (hsa04720)
  Glutamatergic synapse (hsa04724)
  Dopaminergic synapse (hsa04728)
  Alzheimer's disease (hsa05010)
  Amyotrophic lateral sclerosis (ALS) (hsa05014)
  Huntington's disease (hsa05016)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Nicotine addiction (hsa05033)
  Alcoholism (hsa05034)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Unblocking of NMDA receptor, glutamate binding and activation (R-HSA-438066)
  CREB phosphorylation through the activation of CaMKII (R-HSA-442729)
  Ras activation uopn Ca2+ infux through NMDA receptor (R-HSA-442982)
  RAF/MAP kinase cascade (R-HSA-5673001)
  EPHB-mediated forward signaling (R-HSA-3928662)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alpha 1-PI	DMXC1K9	Alpha-1 antitrypsin deficiency	5C5A	Approved	[1]

8 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CERC-301	DMSABRI	Major depressive disorder	6A70.3	Phase 2	[2]
CP-101,606	DMIU19E	Parkinson disease	8A00.0	Phase 2	[3]
ELIPRODIL	DMIOGZM	Multiple sclerosis	8A40	Phase 2	[4]
MIJ821	DMN45RI	Major depressive disorder	6A70.3	Phase 2	[5]
RGH-896	DMCHZAN	Peripheral neuropathy	8C0Z	Phase 2	[6]
EVT100	DMAKWQD	Major depressive disorder	6A70.3	Phase 1	[7]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[8]
Neu-2000	DMNJTLC	Cardiac arrest	MC82	Phase 1	[9]

14 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
EVT-101	DMOYMGV	Neuropathic pain	8E43.0	Discontinued in Phase 2	[10]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[11]
Besonprodil	DMMAFQP	Parkinson disease	8A00.0	Discontinued in Phase 1	[10]
EVT-103	DM9450Z	Major depressive disorder	6A70.3	Discontinued in Phase 1	[12]
DIZOCILPINE	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[13]
L-687414	DM56VPY	N. A.	N. A.	Terminated	[14]
L-689560	DMCVY4U	Neurodegenerative disorder	8A20-8A23	Terminated	[15]
L-695902	DMT1DNS	N. A.	N. A.	Terminated	[14]
L-698532	DMO9HM7	Neurological disorder	6B60	Terminated	[16]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[14]
L-701324	DMAIJSX	Cerebrovascular ischaemia	8B1Z	Terminated	[16]
MDL-105519	DMHUJCI	N. A.	N. A.	Terminated	[17]
RO-25-6981	DM3H921	Cancer related pain	MG30	Terminated	[18]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[19]

101 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+)-HA966	DMKWEAJ	Discovery agent	N.A.	Investigative	[15]
(D)-Ala-Pro-Glu	DMGXTSB	Discovery agent	N.A.	Investigative	[20]
(R)-2-Amino-5-phosphono-pentanoic acid	DMSY4CK	Discovery agent	N.A.	Investigative	[21]
(R)-2-Amino-7-phosphono-heptanoic acid	DM4XEHR	Discovery agent	N.A.	Investigative	[21]
(RS)-(tetrazol-5-yl)glycine	DMYZCRF	Discovery agent	N.A.	Investigative	[15]
1,3-ditolylguanidine	DM04KS1	Discovery agent	N.A.	Investigative	[22]
2-(4-benzyl-piperidin-1-ylmethyl)-1H-indol-6-ol	DMFGCS1	Discovery agent	N.A.	Investigative	[23]
2-(4-Phenoxy-benzyl)-1H-benzoimidazole	DM65IF1	Discovery agent	N.A.	Investigative	[24]
2-(4-Phenoxy-benzyl)-3H-benzoimidazol-4-ol	DM3HANW	Discovery agent	N.A.	Investigative	[24]
2-(4-Phenoxy-benzyl)-3H-benzoimidazol-5-ol	DMFO19B	Discovery agent	N.A.	Investigative	[24]
2-(4-Phenoxy-benzyl)-3H-benzoimidazol-5-ylamine	DMJSBFU	Discovery agent	N.A.	Investigative	[24]
2-Methylamino-succinic acid(NMDA)	DMKP6BM	Discovery agent	N.A.	Investigative	[15]
2-Pyridin-4-yl-1,2,3,4-tetrahydro-isoquinoline	DM5D09Q	Discovery agent	N.A.	Investigative	[25]
3-Benzoyl-7-chloro-4-hydroxy-1H-quinolin-2-one	DMAH4DG	Discovery agent	N.A.	Investigative	[14]
3-Hydroxy-1H-benzo[b]azepine-2,5-dione	DMZSOPU	Discovery agent	N.A.	Investigative	[26]
3-Hydroxy-6-methyl-1H-benzo[b]azepine-2,5-dione	DMYR350	Discovery agent	N.A.	Investigative	[26]
3-Hydroxy-7-nitro-1H-benzo[b]azepine-2,5-dione	DMTEJOY	Discovery agent	N.A.	Investigative	[26]
3-Hydroxy-8-methyl-1H-benzo[b]azepine-2,5-dione	DM7HKIF	Discovery agent	N.A.	Investigative	[26]
3-phenyl-4-hydroxyquinolin-2(1H)-one	DM2C9X8	Discovery agent	N.A.	Investigative	[16]
4,5,7-Trichloro-3-hydroxy-1H-quinolin-2-one	DMXZ9PI	Discovery agent	N.A.	Investigative	[27]
4,6-Dichloro-1H-indole-2-carboxylic acid	DM62XC3	Discovery agent	N.A.	Investigative	[28]
4-(3,4-Dihydro-1H-isoquinolin-2-yl)-quinoline	DMCOJIL	Discovery agent	N.A.	Investigative	[25]
4-Benzyl-1-(2-phenoxy-ethyl)-piperidine	DMQZ0D6	Discovery agent	N.A.	Investigative	[4]
4-Benzyl-1-phenethyl-piperidine hydrochloride	DMAI6X2	Discovery agent	N.A.	Investigative	[29]
4-Bromo-3-hydroxy-1H-quinolin-2-one	DMYOCFX	Discovery agent	N.A.	Investigative	[27]
4-Bromo-5,7-dichloro-3-hydroxy-1H-quinolin-2-one	DM2QJ5A	Discovery agent	N.A.	Investigative	[27]
4-Chloro-3-hydroxy-1H-quinolin-2-one	DMMALY3	Discovery agent	N.A.	Investigative	[27]
4-hydroxy-5-phenylthieno[2,3-b]pyridin-6(7H)-one	DMT3H2X	Discovery agent	N.A.	Investigative	[16]
4-[2-(3-Phenyl-propylamino)-ethyl]-phenol	DM64WSV	Discovery agent	N.A.	Investigative	[29]
4-[2-(4-Benzyl-piperidin-1-yl)-ethoxy]-phenol	DM74G6Q	Discovery agent	N.A.	Investigative	[4]
4-[2-(4-Phenyl-butoxy)-ethyl]-phenol	DML8B3T	Discovery agent	N.A.	Investigative	[29]
4-[2-(4-Phenyl-butylamino)-ethyl]-phenol	DMXLVJW	Discovery agent	N.A.	Investigative	[29]
4-[2-(4-Phenyl-piperidin-1-yl)-ethoxy]-phenol	DM8JM4Q	Discovery agent	N.A.	Investigative	[4]
4-[2-(5-Phenyl-pentylamino)-ethyl]-phenol	DM5J7O8	Discovery agent	N.A.	Investigative	[29]
4-[2-(6-Phenyl-hexylamino)-ethyl]-phenol	DMLCIJX	Discovery agent	N.A.	Investigative	[29]
4-[3-(4-Phenyl-butylamino)-propyl]-phenol	DMOF9YN	Discovery agent	N.A.	Investigative	[30]
4-[3-(5-Phenyl-pentylamino)-propyl]-phenol	DMKDBHN	Discovery agent	N.A.	Investigative	[29]
4-{2-[Ethyl-(4-phenyl-butyl)-amino]-ethyl}-phenol	DMA21GM	Discovery agent	N.A.	Investigative	[29]
5,7-Dichloro-3-hydroxy-1H-quinazoline-2,4-dione	DMUADN4	Discovery agent	N.A.	Investigative	[31]
5,7-Dichloro-4-hydroxy-3-phenyl-1H-quinolin-2-one	DMZJKIU	Discovery agent	N.A.	Investigative	[14]
5,7-Dinitro-1,4-dihydro-quinoxaline-2,3-dione	DMG4UCX	Discovery agent	N.A.	Investigative	[14]
6,7-Dichloro-3-hydroxy-1H-quinazoline-2,4-dione	DMNEJ8W	Discovery agent	N.A.	Investigative	[31]
6-Chloro-1,4-dihydro-quinoxaline-2,3-dione	DMURJ34	Discovery agent	N.A.	Investigative	[32]
6-Methoxy-2-(4-phenoxy-benzyl)-1H-benzoimidazole	DMZP3XJ	Discovery agent	N.A.	Investigative	[24]
6-Nitro-1,4-dihydro-quinoxaline-2,3-dione	DM84CTA	Discovery agent	N.A.	Investigative	[32]
6-Nitro-2-(4-phenoxy-benzyl)-1H-benzoimidazole	DMZTXDV	Discovery agent	N.A.	Investigative	[24]
7-chloro-3-hydroxyquinazoline-2,4-dione	DM3OMLU	Discovery agent	N.A.	Investigative	[33]
8-Bromo-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DMPVU7H	Discovery agent	N.A.	Investigative	[26]
8-Chloro-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DM842L6	Discovery agent	N.A.	Investigative	[26]
8-Ethyl-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DMY8W0K	Discovery agent	N.A.	Investigative	[26]
8-Fluoro-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DMBZSAO	Discovery agent	N.A.	Investigative	[26]
Ala-Pro-Glu	DMTWB54	Discovery agent	N.A.	Investigative	[20]
AP-7	DMBU942	Discovery agent	N.A.	Investigative	[34]
Benzyl 4-aminobutyl(3-aminopropyl)carbamate	DMOKVAT	Discovery agent	N.A.	Investigative	[35]
CGP61594	DM8KFZH	Discovery agent	N.A.	Investigative	[15]
CN-2097	DMJA8I4	Neurological disorder	6B60	Investigative	[15]
Conantokin-G	DMC2IYH	Discovery agent	N.A.	Investigative	[36]
Conantokin-R	DMN4KJI	Discovery agent	N.A.	Investigative	[36]
Conantokins G	DMLHF3E	Discovery agent	N.A.	Investigative	[37]
Conantokins T	DMV6H5S	Discovery agent	N.A.	Investigative	[37]
d-AP5	DMY5OTN	Discovery agent	N.A.	Investigative	[15]
D-aspartic acid	DM7Z892	Discovery agent	N.A.	Investigative	[15]
d-CCPene	DM36D0F	Discovery agent	N.A.	Investigative	[15]
DNQX	DMQXPA5	Discovery agent	N.A.	Investigative	[38]
DQP-1105	DMQLJ3Y	Discovery agent	N.A.	Investigative	[39]
Gly-Amp-Glu	DMO8LAC	Discovery agent	N.A.	Investigative	[20]
Gly-b7Pro-Glu	DM8L09J	Discovery agent	N.A.	Investigative	[20]
Gly-Hyp-Glu	DM8XR4Y	Discovery agent	N.A.	Investigative	[20]
Gly-Pip-Glu	DMM0JA4	Discovery agent	N.A.	Investigative	[20]
H-Gly-D-dmP-Glu-OH	DMX2TGD	Discovery agent	N.A.	Investigative	[40]
H-Gly-dmP-Glu-OH	DMOYQPM	Discovery agent	N.A.	Investigative	[40]
homoquinolinic acid	DMBW5DU	Discovery agent	N.A.	Investigative	[15]
L-aspartic acid	DMWGPO6	Hypokalemia	5C77	Investigative	[15]
LY233053	DMC82DA	Discovery agent	N.A.	Investigative	[15]
N,N'-Bis-(4-butoxy-phenyl)-guanidine	DMLOP2B	Discovery agent	N.A.	Investigative	[22]
N,N'-Bis-(4-butyl-phenyl)-guanidine	DMOS2GH	Discovery agent	N.A.	Investigative	[22]
N,N'-Bis-(4-ethyl-phenyl)-guanidine	DM0CTG7	Discovery agent	N.A.	Investigative	[22]
N,N'-Bis-(4-hexyl-phenyl)-guanidine	DM0RQGU	Discovery agent	N.A.	Investigative	[22]
N,N'-Bis-(4-isopropyl-phenyl)-guanidine	DMM38BC	Discovery agent	N.A.	Investigative	[22]
N,N'-Bis-(4-sec-butyl-phenyl)-guanidine	DMFDXLB	Discovery agent	N.A.	Investigative	[22]
N-(2-methoxybenzyl)cinnamamidine	DM06S5Z	Discovery agent	N.A.	Investigative	[41]
N-(3-phenethoxybenzyl)-4-hydroxybenzamide	DMHZU8K	Discovery agent	N.A.	Investigative	[42]
N-(4-(benzyloxy)phenethyl)pyridin-4-amine	DMIPKNQ	Discovery agent	N.A.	Investigative	[43]
N1-dansyl-spermine	DM76CLF	Discovery agent	N.A.	Investigative	[15]
Nle-Pro-Glu	DM0FA6B	Discovery agent	N.A.	Investigative	[20]
NP93-31	DMMZXRT	Brain injury	NA07.Z	Investigative	[15]
NVP-AAM077	DM9DURZ	Discovery agent	N.A.	Investigative	[44]
Phe-Pro-Glu	DMJMLKA	Discovery agent	N.A.	Investigative	[20]
PHENCYCLIDINE	DMQBEYX	Discovery agent	N.A.	Investigative	[45]
Phenethyl-(3-phenyl-propyl)-amine	DMQWFO1	Discovery agent	N.A.	Investigative	[29]
Phenethyl-(4-phenyl-butyl)-amine	DMFQMHK	Discovery agent	N.A.	Investigative	[29]
Ro 63-1908	DMYVQF5	N. A.	N. A.	Investigative	[46]
RPR-118723	DMLDWCB	Discovery agent	N.A.	Investigative	[19]
Tenocyclidine	DMRM1QV	Discovery agent	N.A.	Investigative	[47]
TRANSTORINE	DMP4T87	Discovery agent	N.A.	Investigative	[28]
UBP141	DM6IG5J	Discovery agent	N.A.	Investigative	[21]
[3H]CGP39653	DMITR7A	Discovery agent	N.A.	Investigative	[15]
[3H]CGS19755	DM7H3JN	Discovery agent	N.A.	Investigative	[15]
[3H]CPP	DMR5UBF	Discovery agent	N.A.	Investigative	[15]
[3H]dizocilpine	DMEC2PF	Discovery agent	N.A.	Investigative	[15]
[3H]MDL105519	DMPKGHB	Discovery agent	N.A.	Investigative	[15]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Parkinson's disease	8A00.0	Substantia nigra tissue	7.51E-01	-0.06	-0.32
Major depressive disorder	6A20	Pre-frontal cortex	1.23E-01	0.14	0.29

References

• [1] NMDA receptor stimulation induces reversible fission of the neuronal endoplasmic reticulum. PLoS One. 2009;4(4):e5250.
• [2] Inhibition of in vivo [(3)H]MK-801 binding by NMDA receptor open channel blockers and GluN2B antagonists in rats and mice. Eur J Pharmacol. 2015 Nov 5;766:1-8.
• [3] NMDA receptors as targets for drug action in neuropathic pain. Eur J Pharmacol. 2001 Oct 19;429(1-3):71-8.
• [4] 4-Hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine: a novel, potent, and selective NR1/2B NMDA receptor antagonist. J Med Chem. 1999 Jul 29;42(15):2993-3000.
• [5] Clinical pipeline report, company report or official report of Cadent Therapeutics.
• [6] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Synthesis, ionotropic glutamate receptor binding affinity, and structure-activity relationships of a new set of 4,5-dihydro-8-heteroaryl-4-oxo-1,2,... J Med Chem. 2001 Sep 13;44(19):3157-65.
• [9] Neu2000, an NR2B-selective, moderate NMDA receptor antagonist and potent spin trapping molecule for stroke. Drug News Perspect. 2010 Nov;23(9):549-56.
• [10] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [11] 4,10-Dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-carboxylic acid derivatives: highly potent and selective AMPA receptors antagonists with... Bioorg Med Chem Lett. 2000 May 15;10(10):1133-7.
• [12] Clinical pipeline report, company report or official report of Evotec.
• [13] Synthesis and evaluation of 6,11-ethanohexahydrobenzo[b]quinolizidines: a new class of noncompetitive N-methyl-D-aspartate antagonists. J Med Chem. 1995 Jun 23;38(13):2483-9.
• [14] Amino acid bioisosteres: design of 2-quinolone derivatives as glycine-site N-methyl-D-aspartate receptor antagonists, Bioorg. Med. Chem. Lett. 3(2):299-304 (1993).
• [15] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 457).
• [16] Synthesis of thieno[2,3-b]pyridinones acting as cytoprotectants and as inhibitors of [3H]glycine binding to the N-methyl-D-aspartate (NMDA) receptor. J Med Chem. 2006 Feb 9;49(3):864-71.
• [17] CoMFA, synthesis, and pharmacological evaluation of (E)-3-(2-carboxy-2-arylvinyl)-4,6-dichloro-1H-indole-2-carboxylic acids: 3-[2-(3-aminophenyl)-2... J Med Chem. 2005 Feb 24;48(4):995-1018.
• [18] Emerging analgesics in cancer pain management. Expert Opin Emerg Drugs. 2005 Feb;10(1):151-71.
• [19] Indeno[1,2-b]pyrazin-2,3-diones: a new class of antagonists at the glycine site of the NMDA receptor with potent in vivo activity. J Med Chem. 2000 Jun 15;43(12):2371-81.
• [20] New Gly-Pro-Glu (GPE) analogues: expedite solid-phase synthesis and biological activity. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1392-6.
• [21] Synthesis and pharmacology of N1-substituted piperazine-2,3-dicarboxylic acid derivatives acting as NMDA receptor antagonists. J Med Chem. 2005 Apr 7;48(7):2627-37.
• [22] Synthesis and pharmacological evaluation of N,N'-diarylguanidines as potent sodium channel blockers and anticonvulsant agents. J Med Chem. 1998 Aug 13;41(17):3298-302.
• [23] Selective NR1/2B N-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides. J Med Chem. 2007 Mar 8;50(5):901-14.
• [24] NR2B-selective N-methyl-D-aspartate antagonists: synthesis and evaluation of 5-substituted benzimidazoles. J Med Chem. 2004 Apr 8;47(8):2089-96.
• [25] 4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and 4-(3,4-dihydro-1H-isoquinolin-2-yl)-quinolines as potent NR1/2B subtype selective NMDA receptor an... Bioorg Med Chem Lett. 2003 May 19;13(10):1759-62.
• [26] Analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione: structure-activity relationship at N-methyl-D-aspartate receptor glycine sites. J Med Chem. 1996 Nov 8;39(23):4643-53.
• [27] 3-Hydroxy-quinolin-2-ones: Inhibitors of [3H]-glycine binding to the site associated with the NMDA receptor, Bioorg. Med. Chem. Lett. 6(5):499-504 (1996).
• [28] 3-(2-carboxyindol-3-yl)propionic acid derivatives: antagonists of the strychnine-insensitive glycine receptor associated with the N-methyl-D-aspart... J Med Chem. 1990 Nov;33(11):2944-6.
• [29] Structure-activity relationships for a series of bis(phenylalkyl)amines: potent subtype-selective inhibitors of N-methyl-D-aspartate receptors. J Med Chem. 1998 Aug 27;41(18):3499-506.
• [30] Structure-activity relationship for a series of 2-substituted 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indoles: potent subtype-selective inhibitors of N-... Bioorg Med Chem Lett. 1999 Jun 7;9(11):1619-24.
• [31] 3-hydroxy-quinazoline-2,4-dione as a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists. Bioorg Med Chem Lett. 2004 May 3;14(9):2345-9.
• [32] 5-(N-oxyaza)-7-substituted-1,4-dihydroquinoxaline-2,3-diones: novel, systemically active and broad spectrum antagonists for NMDA/glycine, AMPA, and... J Med Chem. 1997 Oct 24;40(22):3679-86.
• [33] Structural investigation of the 7-chloro-3-hydroxy-1H-quinazoline-2,4-dione scaffold to obtain AMPA and kainate receptor selective antagonists. Syn... J Med Chem. 2006 Oct 5;49(20):6015-26.
• [34] Bioisosteric replacement of the alpha-amino carboxylic acid functionality in 2-amino-5-phosphonopentanoic acid yields unique 3,4-diamino-3-cyclobut... J Med Chem. 1992 Dec 11;35(25):4720-6.
• [35] Polyamines and the NMDA receptor: modifying intrinsic activities with aromatic substituents. Bioorg Med Chem Lett. 2006 Jun 1;16(11):2837-41.
• [36] Novel conantokins from Conus parius venom are specific antagonists of N-methyl-D-aspartate receptors. J Biol Chem. 2007 Dec 21;282(51):36905-13.
• [37] Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and T. Pain. 2003 Jan;101(1-2):109-16.
• [38] Kynurenic acid derivatives. Structure-activity relationships for excitatory amino acid antagonism and identification of potent and selective antago... J Med Chem. 1991 Apr;34(4):1243-52.
• [39] Mechanism for noncompetitive inhibition by novel GluN2C/D N-methyl-D-aspartate receptor subunit-selective modulators. Mol Pharmacol. 2011 Nov;80(5):782-95.
• [40] The neuroprotective activity of GPE tripeptide analogues does not correlate with glutamate receptor binding affinity. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3396-400.
• [41] Indole-2-carboxamidines as novel NR2B selective NMDA receptor antagonists. Bioorg Med Chem Lett. 2005 Dec 15;15(24):5439-41.
• [42] Structure-activity relationship study of novel NR2B-selective antagonists with arylamides to avoid reactive metabolites formation. Bioorg Med Chem Lett. 2007 Oct 15;17(20):5537-42.
• [43] Identification and characterization of 4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]piperidine-1-carboxylate, an orally bioavailable, brain penetr... J Med Chem. 2007 Feb 22;50(4):807-19.
• [44] Relating NMDA receptor function to receptor subunit composition: limitations of the pharmacological approach. J Neurosci. 2006 Feb 1;26(5):1331-3.
• [45] Synthesis and biological activity of conformationally restricted analogs of milnacipran: (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopro... J Med Chem. 1996 Nov 22;39(24):4844-52.
• [46] Pharmacological characterization of Ro 63-1908 (1-[2-(4-hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol), a novel subtype-selective N-methyl-D-aspartate antagonist. J Pharmacol Exp Ther. 2002 Sep;302(3):940-8.
• [47] The binding of [3H]thienyl cyclohexylpiperidine ([3H]TCP) to the NMDA-phencyclidine receptor complex. Neuropharmacology. 1989 Jan;28(1):1-7.