85375-15-1

85375-15-1 structure

Name: 1-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylicacidhydrochloride；SKF89976AHCl
Chemical Name: 1-(4,4-diphenylbut-3-enyl)piperidine-3-carboxylic acid,hydrochloride
CAS Number: 85375-15-1
Molecular Formula: C₂₂H₂₆ClNO₂
Molecular Weight: 371.90000
Catalog: Signaling Pathways Membrane Transporter/Ion Channel GABA Receptor
Create Date: 2018-12-25 22:48:40
Modify Date: 2024-01-31 18:23:28
SKF89976A hydrochloride is a selective GABA transporter (GAT-1) inhibitor with IC50s of 0.28 μM, 137.34 μM and 202.8 μM for GAT-1, GAT-2 and GAT-3 in CHO cells, respectively.

Name	1-(4,4-diphenylbut-3-enyl)piperidine-3-carboxylic acid,hydrochloride
Synonyms	S1589_Selleck 1-(4,4-Diphenylbut-3-en-1-yl)piperidine-3-carboxylic acid hydrochloride (1:1) 1-(4,4-Diphenyl-3-buten-1-yl)-3-piperidinecarboxylic acid hydrochloride (1:1) 3-Piperidinecarboxylic acid, 1-(4,4-diphenyl-3-buten-1-yl)-, hydrochloride (1:1) SKF 89976A SKF89976A (hydrochloride) 1-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylicacidhydrochloride；SKF89976AHCl

Description	SKF89976A hydrochloride is a selective GABA transporter (GAT-1) inhibitor with IC50s of 0.28 μM, 137.34 μM and 202.8 μM for GAT-1, GAT-2 and GAT-3 in CHO cells, respectively.
Related Catalog	Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor Signaling Pathways >> Neuronal Signaling >> GABA Receptor Research Areas >> Neurological Disease
Target	IC50: 0.28 μM (GAT-1), 137.34 μM (GAT-2), 202.8 μM (GAT-3)[1]
In Vitro	SKF89976A has a weak antiallodynic action. SKF89976A weakly inhibits serotonin transporter (SERT), noradrenaline transporter (NET), and dopamine transporter (DAT) in chinese hamster ovary (CHO) cells stably expressing each transporter using a substrate uptake assay, with IC50 values of 3514 , 202.13, and 728.8, respectively[1]. SKF89976A is a GABA-transport blocker. GABA (1 mM) elicited an inward current that is completely suppressed by the GABA transport inhibitors tiagabine (10 μM) and SKF89976A (100 μM), but is unaffected by 100 μM picrotoxin. 100 μM SKF 89976-A is known to block the transport of GABA into cells, completely eliminated the GABA-elicited current in a reversible fashion[2]. SKF89976A is a nontransportable blockers of GAT-1. SKF89976-A also suppresses baseline inward currents that likely result from tonic GAT activation by background GABA. SKF89976A (100 μM) reversibly reduces GAT currents in every studied cell by 67.9±4.4% (n=19). Intracellular perfusion of 20 μM SKF89976-A progressively reduced and blocked GABA-induced GAT currents without blocking GABAAR-mediated currents (n=4)[3].
In Vivo	SKF89976A produces a weak antiallodynic response when administered i.v. (0.3 mg/kg). The i.t. injection of SKF89976A dose-dependently ameliorates the reduction in the withdrawal threshold in PSL model mice[1].
Cell Assay	CHO cells stably expressing the mouse GAT subtypes, rat serotonin transporter (SERT), rat noradrenaline transporter (NET), and rat dopamine transporter (DAT) are incubated with 10 nM tritium-labeled GABA or monoamines for 10 min in the absence or presence of various concentrations of the GAT inhibitors (e.g., SKF89976A) tested. Values presented for SERT, NET, and DAT are the mean±S.E.M. for 3 experiments, with each being performed in duplicate[1].
Animal Admin	Mice[1] 5-week-old ddY male mice, weighing 25-30 g at the beginning of the study are used. Mice are administered NNC05-2090, SKF89976A (0.3 mg/kg, i.p.), (S)-SNAP5114, or amitriptyline. The composition of ACSF (in mM) is 142 mM NaCl, 5 mM KCl, 2 mM CaCl2, 2 mM MgCl2, 1.25 mM NaH2PO4, 10 mM d-glucose, 10 mM HEPES, and 0.05% fatty acid-free bovine serum albumin (pH 7.4). The intraperitoneal (i.p.) injection of drugs is administered in a volume of 0.1 mL/10 g body weight. When given intravenously (i.v.), solutions are injected into the tail vein in a volume of 0.1 mL/10 g body weight. The head of a mouse is placed into a plastic cap and the body is held with one hand for an intrathecal (i.t.) injection. A 27-gauge needle attached to a Hamilton microsyringe is inserted into the subarachnoid space between the L5 and L6 vertebrae of the conscious mouse and 5 mL of the drug solution is slowly injected[1].
References	[1]. Jinzenji A, et al. Antiallodynic action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a betaine/GABA transporter inhibitor. J Pharmacol Sci. 2014;125(2):217-26. [2]. Kreitzer MA, et al. Glutamate modulation of GABA transport in retinal horizontal cells of the skate. J Physiol. 2003 Feb 1;546(Pt 3):717-31. [3]. Barakat L, et al. GAT-1 and reversible GABA transport in Bergmann glia in slices. J Neurophysiol. 2002 Sep;88(3):1407-19.

Boiling Point	531.4ºC at 760 mmHg
Molecular Formula	C₂₂H₂₆ClNO₂
Molecular Weight	371.90000
Flash Point	275.2ºC
Exact Mass	371.16500
PSA	40.54000
LogP	5.04490
Storage condition	2-8℃

Personal Protective Equipment	Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
RIDADR	NONH for all modes of transport
HS Code	2933399090

85375-14-0

~65%

85375-15-1

Literature: Ali, Fadia E.; Bondinell, William E.; Dandridge, Penelope A.; Frazee, James S.; Garvey, Eleanor; et al. Journal of Medicinal Chemistry, 1985 , vol. 28, # 5 p. 653 - 660

Precursor 1
85375-14-0
DownStream 0

HS Code	2933399090
Summary	2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

1158522-08-7	940364-43-2
134104-43-1	131615-57-1
6906-52-1	930439-75-1
90056-53-4	1018584-77-4
1375289-11-4	1384805-69-9