LE300 | CAS#274694-98-3 | D1-like receptor antagonist

MedKoo Cat#: 462138 | Name: LE300

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

LE300 is a novel type of a nanomolar dopamine receptor antagonist combining structural core elements of dopamine and serotonin, and may become useful as positrone emission tomography ligand. LE300 shows nanomolar affinities to the hD1 receptor family, suppresses in vivo spontanous locomotor activity and attenuates locomotor activity induced by cocaine.

Chemical Structure

LE300

CAS#274694-98-3

Theoretical Analysis

MedKoo Cat#: 462138

Name: LE300

CAS#: 274694-98-3

Chemical Formula: C20H22N2

Exact Mass: 290.1783

Molecular Weight: 290.41

Elemental Analysis: C, 82.72; H, 7.64; N, 9.65

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 550.00	2 Weeks

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Related CAS #

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Synonym

LE300; LE-300; LE 300;

IUPAC/Chemical Name

6,7,8,9,14,15-hexahydro-7-methyl-5H-indolo[3,2-f][3]benzazecine

InChi Key

YEWGIGCYIAMFMA-UHFFFAOYSA-N

InChi Code

InChI=1S/C20H22N2/c1-22-12-10-15-6-2-3-7-16(15)14-20-18(11-13-22)17-8-4-5-9-19(17)21-20/h2-9,21H,10-14H2,1H3

SMILES Code

CN1CCC2=C(CC3=C(C=CC=C3)CC1)NC4=C2C=CC=C4

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

LE 300 is a potent and selective dopamine D1-like receptor antagonist with Kis of 1.9 nM and 7.5 nM in CHO cell membranes expressing human dopamine D1 and D5 receptors, respectively.

In vitro activity:

LE300 was the most potent compound with a 10- to 20-fold selectivity for D1 over D2L receptors as measured in equilibrium binding experiments [competition radioligand binding: K(i)(D1)=1.9 nM, K(i)(D2L)=44.7 nM; [(35)S]GTPgammaS-binding: K(i)(D1)=1.8 nM, K(i)(D2L)=21.5 nM]. LE300 is currently under investigation for usefulness as positrone emission tomography ligand. Reference: Naunyn Schmiedebergs Arch Pharmacol. 2002 Dec;366(6):543-50. https://pubmed.ncbi.nlm.nih.gov/12444495/

In vivo activity:

In binding assays with rat striatal receptors, 7-methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2, 3-g]azecine (LE 300) proved to be of high affinity for the D(1) binding site (K(i) = 0.08 nmol for displacement of [(3)H]SCH23390), being superior in this assay to standards such as butaclamol and SCH23390. This compound was characterized as a dopamine antagonist by conditioned avoidance response test with mice. Reference: J Med Chem. 2000 May 18;43(10):2079-81. https://pubmed.ncbi.nlm.nih.gov/10821720/

	Solvent	mg/mL	mM
Solubility
	DMSO	29.0	100.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 290.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Xu P, Gildea JJ, Zhang C, Konkalmatt P, Cuevas S, Bigler Wang D, Tran HT, Jose PA, Felder RA. Stomach gastrin is regulated by sodium via PPAR-α and dopamine D1 receptor. J Mol Endocrinol. 2020 Feb;64(2):53-65. doi: 10.1530/JME-19-0053. PMID: 31794424; PMCID: PMC7654719. 2. Kassack MU, Höfgen B, Decker M, Eckstein N, Lehmann J. Pharmacological characterization of the benz[d]indolo[2,3-g]azecine LE300, a novel type of a nanomolar dopamine receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol. 2002 Dec;366(6):543-50. doi: 10.1007/s00210-002-0641-z. Epub 2002 Oct 11. PMID: 12444495. 3. Hefnawy M, Mohamed M, Abunassif M, Alanazi A, Al-Majed A, Jochen L, Mostafa GA. Spectrofluorimetric determination of dopamine receptor antagonist LE 300 in mice plasma. Luminescence. 2016 Feb;31(1):63-6. doi: 10.1002/bio.2923. Epub 2015 Apr 19. PMID: 25892547. 4. Witt T, Hock FJ, Lehmann J. 7-Methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2,3-g]azecine: a new heterocyclic system and a new lead compound for dopamine receptor antagonists. J Med Chem. 2000 May 18;43(10):2079-81. doi: 10.1021/jm9911478. PMID: 10821720.

In vitro protocol:

In vivo protocol:

1. Hefnawy M, Mohamed M, Abunassif M, Alanazi A, Al-Majed A, Jochen L, Mostafa GA. Spectrofluorimetric determination of dopamine receptor antagonist LE 300 in mice plasma. Luminescence. 2016 Feb;31(1):63-6. doi: 10.1002/bio.2923. Epub 2015 Apr 19. PMID: 25892547. 2. Witt T, Hock FJ, Lehmann J. 7-Methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2,3-g]azecine: a new heterocyclic system and a new lead compound for dopamine receptor antagonists. J Med Chem. 2000 May 18;43(10):2079-81. doi: 10.1021/jm9911478. PMID: 10821720.

1: Hefnawy MM, Attwa MW, Alzamil AA, El-Gendy MA, El-Azab AS, Jardan YAB, El- Gamal AA. A Liquid Chromatography Tandem Mass Spectrometry Method for the Simultaneous Estimation of the Dopamine Receptor Antagonist LE300 and Its N-methyl Metabolite in Plasma: Application to a Pharmacokinetic Study. Molecules. 2023 Feb 6;28(4):1553. doi: 10.3390/molecules28041553. PMID: 36838539; PMCID: PMC9964957. 2: Dai F, Song JH, Hong YP, Bai X, Sohn WM, Hong SJ. Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production. PLoS Negl Trop Dis. 2020 Mar 30;14(3):e0008220. doi: 10.1371/journal.pntd.0008220. PMID: 32226018; PMCID: PMC7145267. 3: Xu P, Gildea JJ, Zhang C, Konkalmatt P, Cuevas S, Bigler Wang D, Tran HT, Jose PA, Felder RA. Stomach gastrin is regulated by sodium via PPAR-α and dopamine D1 receptor. J Mol Endocrinol. 2020 Feb;64(2):53-65. doi: 10.1530/JME-19-0053. PMID: 31794424; PMCID: PMC7654719. 4: Moriya T, Nakayama K, Nakamura S, Mochizuki A, Ofuji T, Shirota T, Inoue T. Enhancement of swallowing motor activity by the ACE inhibitor imidapril in an arterially perfused rat preparation. Eur J Pharmacol. 2019 Oct 15;861:172601. doi: 10.1016/j.ejphar.2019.172601. Epub 2019 Aug 14. PMID: 31421086. 5: Li S, Song JH, Kim TI, Yoo WG, Won MH, Dai F, Hong SJ. Chemotactic migration of newly excysted juvenile Clonorchis sinensis is suppressed by neuro- antagonists. PLoS Negl Trop Dis. 2019 Aug 13;13(8):e0007573. doi: 10.1371/journal.pntd.0007573. PMID: 31408466; PMCID: PMC6691982. 6: Hefnawy M, Mohamed M, Abunassif M, Alanazi A, Al-Majed A, Jochen L, Mostafa GA. Spectrofluorimetric determination of dopamine receptor antagonist LE 300 in mice plasma. Luminescence. 2016 Feb;31(1):63-6. doi: 10.1002/bio.2923. Epub 2015 Apr 19. PMID: 25892547. 7: Al-Majed AA, Hefnawy MM, Mohammed MS, Attia SM, Lehmann J. Selective microemulsion liquid chromatography analysis of dopamine receptor antagonist LE300 and its N-methyl metabolite in mouse sera by using a monolithic silica column. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 May 1;989:104-11. doi: 10.1016/j.jchromb.2015.03.005. Epub 2015 Mar 14. PMID: 25817262. 8: Arimitsu E, Ogasawara T, Takeda H, Sawasaki T, Ikeda Y, Hiasa Y, Maeyama K. The ligand binding ability of dopamine D1 receptors synthesized using a wheat germ cell-free protein synthesis system with liposomes. Eur J Pharmacol. 2014 Dec 15;745:117-22. doi: 10.1016/j.ejphar.2014.10.011. Epub 2014 Oct 16. PMID: 25446930. 9: Robaa D, Kretschmer R, Siol O, Abulazm SE, Elkhawass E, Lehmann J, Enzensperger C. Residues at the indole-NH of LE300 modulate affinities and selectivities for dopamine receptors. Arch Pharm (Weinheim). 2011 Jan;344(1):28-36. doi: 10.1002/ardp.201000121. Epub 2010 Nov 11. PMID: 21213349. 10: Han P, Whelan PJ. Modulation of AMPA currents by D(1)-like but not D(2)-like receptors in spinal motoneurons. Neuroscience. 2009 Feb 18;158(4):1699-707. doi: 10.1016/j.neuroscience.2008.11.040. Epub 2008 Dec 7. PMID: 19110039. 11: Decker M, Lehmann J. LE300--new results on its ability to antagonize the discriminative stimulus effects of cocaine. Pharmazie. 2006 Mar;61(3):248-50. PMID: 16599272. 12: Hoefgen B, Decker M, Mohr P, Schramm AM, Rostom SA, El-Subbagh H, Schweikert PM, Rudolf DR, Kassack MU, Lehmann J. Dopamine/serotonin receptor ligands. 10: SAR Studies on azecine-type dopamine receptor ligands by functional screening at human cloned D1, D2L, and D5 receptors with a microplate reader based calcium assay lead to a novel potent D1/D5 selective antagonist. J Med Chem. 2006 Jan 26;49(2):760-9. doi: 10.1021/jm050846j. PMID: 16420061. 13: Decker M, Schleifer KJ, Nieger M, Lehmann J. Dopamine/serotonin receptor ligands. Part VIII: the dopamine receptor antagonist LE300 - modelled and X-ray structure plus further pharmacological characterization, including serotonin receptor binding, biogenic amine transporter testing and in vivo testings. Eur J Med Chem. 2004 Jun;39(6):481-9. doi: 10.1016/j.ejmech.2004.02.001. PMID: 15183906. 14: Kassack MU, Höfgen B, Decker M, Eckstein N, Lehmann J. Pharmacological characterization of the benz[d]indolo[2,3-g]azecine LE300, a novel type of a nanomolar dopamine receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol. 2002 Dec;366(6):543-50. doi: 10.1007/s00210-002-0641-z. Epub 2002 Oct 11. PMID: 12444495. 15: Abadi AH, Lankow S, Hoefgen B, Decker M, Kassack MU, Lehmann J. Dopamine/serotonin receptor ligands, part III [1]: synthesis and biological activities of 7, 7'-alkylene-bis-6, 7, 8, 9, 14, 15-hexahydro-5H-benz[d]indolo[2, 3-g]azecines -- application of the bivalent ligand approach to a novel type of dopamine receptor antagonist. Arch Pharm (Weinheim). 2002 Aug;335(8):367-73. doi: 10.1002/1521-4184(200211)335:8<367::AID-ARDP367>3.0.CO;2-C. PMID: 12397620. 16: Kassack MU, Höfgen B, Lehmann J, Eckstein N, Quillan JM, Sadée W. Functional screening of G protein-coupled receptors by measuring intracellular calcium with a fluorescence microplate reader. J Biomol Screen. 2002 Jun;7(3):233-46. doi: 10.1177/108705710200700307. PMID: 12097186.