| Identification | Back Directory | [Name]
A971432 | [CAS]
1240308-45-5 | [Synonyms]
A971432
A971432,A 971432
A-971432 >=95% (HPLC)
1-(4-((3,4-dichlorobenzyl)oxy)benzyl)azetidine-3-carboxylic acid
1-[[4-[(3,4-Dichlorophenyl)methoxy]phenyl]methyl]-3-azetidinecarboxylic acid | [EINECS(EC#)]
827-461-8 | [Molecular Formula]
C18H17Cl2NO3 | [MDL Number]
MFCD30182357 | [MOL File]
1240308-45-5.mol | [Molecular Weight]
366.24 |
| Chemical Properties | Back Directory | [Boiling point ]
520.0±50.0 °C(Predicted) | [density ]
1.402±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
Slightly soluble in chloroform | [form ]
powder | [pka]
2.70±0.20(Predicted) | [color ]
white to beige |
| Hazard Information | Back Directory | [Uses]
A 971432 is used in the preparation of benzylazetidinecarboxylate derivatives as agonists and antagonists of the S1P5 receptor. | [Biochem/physiol Actions]
A-971432 is an orally bioavailable, non-clastogenic, azetidinecarboxylate compound that acts as a highly potent and selective sphingosine-1-phosphate receptor 5 agonist (IC50?= 6 nM/S1P5, 362 nM/S1P1 and >10 μM/S1P3 in a radio-ligand binding assay) without affect the activity of 129 protein kinases (IC50?>10 μM). A-971432 is shown to enhance blood-brain barrier integrity and reverse lipid accumulation and age-related cognitive decline in mice in vivo with good pharmacokinetics (t1/2??= 5.7 h; Cmax?= 2,500 ng/ml; AUC = 35,000 ng.h/ml at 10 mg/kg, p.o. in CD1 mice). Likewise, oral gavage showed good plasma exposure and no sign of lymphopenia in rats (10, 30, and 100 mg/kg. | [in vivo]
A-971432 (1, 2 mg/kg; p.o.) shows excellent PK characteristics and oral bioavailability[1].
A-971432 (0.1 mg/kg; P.o.; daily for 21 days) shows pro-cognitive impact in a dose-dependent manner[1].
A-971432 (11 weeks R6/2 mice; 0.1 mg/kg; i.p.) increases the phosphorylation of AKT and ERK and significantly incremented the levels of BDNF in the cortex[2].
A-971432 (0.1 mg/kg; i.p.) attenuates the classic progressive BBB leakage and therefore the FITC-albumin extravasation in striatal parenchyma, and protects blood–brain barrier (BBB) homeostasis and suppresses aggregation of mHtt in the CNS blood vessels[2].
A-971432 (0.1 mg/kg; i.p.; daily for 4 weeks) prevents the worsening of motor deficit in symptomatic R6/2 mice by chronic infusion[2].
Pharmacokinetic Parameters of A-971432 in Balb/C mice, SD rat, beagle dog, cyno monkey[1].
| | | | IV | PO | | species | dose (mg/kg) | sample analyzed) | protein binding (%) | t1/2 (h) | AUC (ng.h/mL) | VL (L/h/kg) | Vss(L/kg) | t1/2 (h) | tmax (h) | Cmax (ng/mL) | AUC (ng.h/mL) | F(%) | | BALB/C mouse | 2 | plasma | 93 | 7.6 | 8500 | 0.24 | 1.9 | 7.4 | 2.0 | 300 | 4800 | 57 | | BALB/C mouse | 2 | brain | nd | 9.8 | 3200 (Cmax=133 ng/nL) | nd | nd | 10 | 2-24 | 43 | 1600 | 56 | | SD rat | 1 | plasm | 93 | 9.0 | 6400 | 0.16 | 1.3 | 14 | 4.3 | 400 | 8700 | >100 | | SD rat | 2 | brain | 99.5 | nd | nd | nd | nd | 15 | 8 | 120 | 3100 | nd | | beagle dog | 1 | plasma | 96 | 9.3 | 12000 | 0.09 | 1.2 | 10 | 1.5 | 690 | 11000 | 92 | | cyno monkey | 1 | plasma | 97 | 3.5 | 6400 | 0.16 | 0.82 | 6.7 | 1.7 | 650 | 5500 | 86 |
Balb/C mice, SD rat, beagle dog, cyno monkey; p.o. or i.v.; 2 mg/kg for Balb/C mice, SD rat; 1mg/kg for SD rat, beagle dog, cyno monkey [1].
| Animal Model: | Balb/C mice, SD rat, beagle dog, cyno monkey[1] | | Dosage: | 1, 2 mg/kg | | Administration: | P.o. or i.v. | | Result: | Showed high oral bioavailability, high exposure, low clearance, a long half-life. |
| Animal Model: | Male C57BL6J mice[1] | | Dosage: | 0.1 mg/kg | | Administration: | P.o.; daily for 21 days | | Result: | Showed pro-cognitive impact in a dose-dependent manner. |
| Animal Model: | 7-week R6/2 mice[2] | | Dosage: | 0.1 mg/kg | | Administration: | I.p.; daily for 4 weeks | | Result: | Restored normal motor function within the first week of treatment, and preserved them from the gradual motor deficit, classically occurring during the disease, for the entire period of the treatment. |
| Animal Model: | 4-week R6/2 mice[2] | | Dosage: | 0.1 mg/kg | | Administration: | I.p., daily for 2 weeks | | Result: | Preserved BBB integrity and delayed the onset of motor symptoms in R6/2 mice and suppressed aggregation of mHtt in the CNS blood vessels. |
| [storage]
Store at RT |
|
| Company Name: |
BOC Sciences
|
| Tel: |
1-631-485-4226; 16314854226 |
| Website: |
https://www.bocsci.com |
| Company Name: |
Sigma-Aldrich
|
| Tel: |
021-61415566 800-8193336 |
| Website: |
https://www.sigmaaldrich.cn |
| Company Name: |
Energy Chemical
|
| Tel: |
021-58432009 400-005-6266 |
| Website: |
http://www.energy-chemical.com |
| Company Name: |
R&D Systems, Inc
|
| Tel: |
18003437475 18003437475 |
| Website: |
www.rndsystems.com |
| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
|