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170151-24-3 molecular structure
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5-(aminomethyl)-1-[(2S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-2,3-dihydro-1H-imidazole-2-thione hydrochloride

ChemBase ID: 73199
Molecular Formular: C14H16ClF2N3S
Molecular Mass: 331.8117464
Monoisotopic Mass: 331.07215265
SMILES and InChIs

SMILES:
c1(cc(c2c(c1)C[C@H](CC2)n1c(c[nH]c1=S)CN)F)F.Cl
Canonical SMILES:
NCc1c[nH]c(=S)n1[C@H]1CCc2c(C1)cc(cc2F)F.Cl
InChI:
InChI=1S/C14H15F2N3S.ClH/c15-9-3-8-4-10(1-2-12(8)13(16)5-9)19-11(6-17)7-18-14(19)20;/h3,5,7,10H,1-2,4,6,17H2,(H,18,20);1H/t10-;/m0./s1
InChIKey:
DIPDUAJWNBEVOY-PPHPATTJSA-N

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CBID:73199 http://www.chembase.cn/molecule-73199.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
5-(aminomethyl)-1-[(2S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-2,3-dihydro-1H-imidazole-2-thione hydrochloride
IUPAC Traditional name
nepicastat hydrochloride
Synonyms
SYN117
Nepicastat hydrochloride
CAS Number
170151-24-3
PubChem SID
162038119
PubChem CID
9840545

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID Price
Selleck Chemicals
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Data Source Data ID
PubChem 9840545 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Rotatable Bonds Lipinski's Rule of Five true 
Acid pKa 10.299601  H Acceptors
H Donor LogD (pH = 5.5) 0.047576632 
LogD (pH = 7.4) 1.7038869  Log P 2.6367137 
Molar Refractivity 79.6337 cm3 Polarizability 29.921957 Å3
Polar Surface Area 41.29 Å2

PROPERTIES

PROPERTIES

Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Storage Condition
-20°C expand Show data source
Target
Dopamine receptor expand Show data source
Salt Data
HCL expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals
Selleck Chemicals - S2695 external link
Research Area
Description Cancer
Biological Activity
Description Nepicastat hydrochloride is a novel, potent and selective inhibitor of both bovine and human dopamine-β-hydroxylase with IC50 of 8.5 nM and 9 nM, respectively.
Targets Bovine dopamine-beta-hydroxylase Human dopamine-beta-hydroxylase
IC50 8.5 nM [1] 9 nM [1]
In Vitro In vitro, Nepicastat hydrochloride shows the selective and concentration-dependent inhibition effects on bovine and human dopamine-beta-hydroxylase activity with IC50 of 8.5 nM and 9.0 nM, respectively. While Nepicastat hydrochloride has negligible affinity for twelve other enzymes and thirteen neurotransmitter receptors. [1]
In Vivo In the artery, left ventricle and cerebral cortex of spontaneously hypertensive rats (SHRs), Nepicastat hydrochloride reduces noradrenaline content, and increases dopamine content and dopamine/noradrenaline ratio in a dose-dependent manner. In addition, Nepicastat hydrochloride also produces the similar effects on noradrenaline, dopamine and dopamine/noradrenaline ratio in tissues and plasma of beagle dogs. [1] In inactin-anesthetized SHRs, Nepicastat hydrochloride (3 mg/kg, i.v.) produces the antihypertensive effects and causes a significant decrease in renal vascular resistance (38%) and an increase in renal blood flow (22%). [2] In dogs with chronic heart failure, low-dose Nepicastat hydrochloride (0.5 mg/kg) prevents left ventricular (LV) dysfunction and remodeling, and combination therapy of Nepicastat hydrochloride and enalapril results in additional improvements in all morphological features. [3] In rat brain, Nepicastat hydrochloride at a dose of 50 mg/kg ( i.p.) leads to the reduction of norepinephrine (NE) and blocks cocaine-primed reinstatement of cocaine seeking. [4]
Clinical Trials Nepicastat hydrochloride is currently in Phase II clinical trials in patients with Posttraumatic Stress Disorder.
Features
Protocol
Kinase Assay [1]
In vitro studies Bovine and human dopamine-beta-hydroxylase activity are assayed by measuring the conversion of tyramine to octopamine. Human dopamine-beta-hydroxylase is purified from the culture medium of the neuroblastoma cell line SK-N-SH. The assay is performed at pH 5.2 and 32°C in a medium containing 0.125 M sodium acetate, 10 mM fumarate, 0.5 ± 2 μM CuSO4, 0.1 mg/mL catalase, 0.1 mM tyramine and 4 mM ascorbate. In a typical assay, 0.5 ± 1 mu of enzyme are added to the reaction mixture and, subsequently, a substrate mixture containing catalase, tyramine and ascorbate is added to initiate the reaction (final volume of 0.2 mL). Samples are incubated with or without the appropriate concentration of nepicastat (RS-25560-197, S-enantiomer) or RS-25560-198 (R-enantiomer) at 37 °C for 30-40 minutes. The reaction is quenched by the stop solution containing 25 mM EDTA and 240 μM 3-hydroxytyramine (internal standard). The samples are analysed for octopamine by reverse phase high pressure liquid chromatography (h.p.l.c.) with ultraviolet (u.v.)-detection at 280 nM. The h.p.l.c. run is carried out at a flow rate of 1 mL/min with a LiChroCART 125-4 RP-18 column and isocratic elution with 10 mM acetic acid, 10 mM 1-heptane sulphonic acid, 12 mM tetrabutyl ammonium phosphate and 10% methanol. The remaining % activity is calculated based on controls (without RS 25560), corrected with internal standards and fitted to a non-linear four-parameter concentration-response curve. The activity of nepicastat at twelve selected enzymes and receptors is determined by use of established assays. Binding data are analysed by iterative curve-fitting to a four parameter logistic equation. Ki values are calculated from IC50 values by the Cheng-Pruso? equation. Enzyme inhibitory activity is expressed as IC50 (concentration required to produce 50% inhibition of enzyme activity).
Animal Study [1]
Animal Models Spontaneously hypertensive rats (SHRs).
Formulation Nepicastat hydrochloride is dissolved in distilled water.
Doses ≤100 mg/kg
Administration Administered via p.o.
References
[1] Stanley WC, et al. Br J Pharmacol. 1997, 121(8), 1803-1809.
[2] Stanley WC, et al. J Cardiovasc Pharmacol. 1998, 31(6), 963-970.
[3] Sabbah HN, et al. Circulation. 2000, 102(16), 1990-1995.
[4] Schroeder JP, et al. Neuropsychopharmacology. 2010, 35(12), 2440-2449.

PATENTS

PATENTS

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INTERNET

INTERNET

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