| Identification | Back Directory | [Name]
3-CHLORO-5-HYDROXY-BENZOIC ACID | [CAS]
53984-36-4 | [Synonyms]
3-chloro-5-hydroxy BA
GPR81 Agonist, 3Cl-5OH-BA
5-Chloro-m-salicylic Acid
3-CHLORO-5-HYDROXY-BENZOIC ACID
5-(hydroxy)-3-chlorobenzoic acid
Benzoic acid, 3-chloro-5-hydroxy-
GPR81 Agonist, 3Cl-5OH-BA - CAS 53984-36-4 - Calbiochem | [Molecular Formula]
C7H5ClO3 | [MDL Number]
MFCD04114327 | [MOL File]
53984-36-4.mol | [Molecular Weight]
172.57 |
| Chemical Properties | Back Directory | [Melting point ]
244.0 to 248.0 °C | [Boiling point ]
364.8±27.0 °C(Predicted) | [density ]
1.536±0.06 g/cm3(Predicted) | [storage temp. ]
room temp | [solubility ]
DMSO: soluble15mg/mL (clear solution) | [form ]
powder | [pka]
3.71±0.10(Predicted) | [color ]
white to beige | [InChI]
InChI=1S/C7H5ClO3/c8-5-1-4(7(10)11)2-6(9)3-5/h1-3,9H,(H,10,11) | [InChIKey]
RJOLIYHZZKAIET-UHFFFAOYSA-N | [SMILES]
C(O)(=O)C1=CC(O)=CC(Cl)=C1 | [CAS DataBase Reference]
53984-36-4 |
| Hazard Information | Back Directory | [Uses]
5-Chloro-m-salicylic Acid was studied as a potential selective lactate receptor (GPR81) agonists with antilipolytic effects. | [Uses]
GPR81, also known as hydroxycarboxylic acid receptor 1 (HCAR1), is a recently de-orphanized receptor that is activated by lactic acid (EC50 ~ 1.5 mM) but not by other hydroxycarboxylic acids. 3-chloro-5-hydroxy Benzoic Acid (3-chloro-5-hydroxy BA) is an agonist of GPR81 (EC50 = 16 μM) that is inactive against the related GPR109a (HCAR2) receptor. It is similarly effective at GPR81 receptors from a variety of mammalian species and is bioavailable, stimulating lipolysis (increased serum free fatty acids) in mice fed high fat chow for 10 weeks. 3-chloro-5-hydroxy BA, like lactate, blocks basal ghrelin secretion by primary gastric mucosal cells.[Cayman Chemical] | [Biological Activity]
3-chloro-5-hydroxy ba is a gpr81 agonist.gpr81 (hca1) is a member of g-protein-coupled receptors (gpcrs). gpr81 is predominantly expressed on adipocytes and is activated by the endogenous ligands 2-hydroxypropanoate (lactate). stimulation of gpr81 in adipose tissue lead to a decrease in the lipolysis of triglycerides by hormone-sensitive lipase, which resulted in reduced transport of fatty acids to the liver and a decrease in hepatic triglycerides [1]. | [Synthesis]
The general procedure for the synthesis of 3-chloro-5-hydroxybenzoic acid from 3-chloro-5-methoxybenzoic acid was as follows: alumina (1.65 g, 60 mmol) and iodine (21 g, 82 mmol) were refluxed in toluene (200 mL) for 2 hours. Subsequently, 3-chloro-5-methoxybenzoic acid (11.2 g, 60.2 mmol) and tetrabutylammonium iodide (1.5 g, 4 mmol) dissolved in toluene (50 mL) were added and the mixture continued to reflux for 2 hours. After completion of the reaction, the mixture was cooled to room temperature and post-extraction treatment afforded 8.7 g, 50 mmol of 3-chloro-5-hydroxybenzoic acid (yield: 83%). The product was characterized by 1H-NMR (300 MHz; acetone-d6): δ 9.27 (s, 1H), 7.48 (m, 1H), 7.44 (m, 1H), 7.11 (m, 1H). | [in vitro]
in the hgpr81 assay, 3-chloro-5-hydroxybenzoic acid showed the potency against gpr81 with an ec50 of 16 μm. the ec50 of 3-chloro-5-hydroxybenzoic acid against monkey gpr81, dog gpr81, rat gpr81, mouse gpr81, and hamster gpr81 was 17 μm, 67 μm, 7 μm, 22 μm and 27 μm, respectively [1]. 3-chloro-5-hydroxy ba blocked basal ghrelin secretion by primary gastric mucosal cells [2]. | [in vivo]
in mice, oral administration of 3-chloro-5-hydroxybenzoic acid at 30 mg/kg provided a cmax of 67 μm at approximately 3-fold over the in vitro ec50 with an aucinf of 54 h μm and a short t1/2 of 1.5 h, and the 100 mg/kg p.o dose attained a cmax of 342 μm at greater than 15-fold over the observed in vitro ec50 [1]. | [storage]
Store at RT | [References]
[1]. dvorak c a, liu c, shelton j, et al. identification of hydroxybenzoic acids as selective lactate receptor (gpr81) agonists with antilipolytic effects[j]. acs medicinal chemistry letters, 2012, 3(8): 637-639.
[2]. engelstoft m s, park w, sakata i, et al. seven transmembrane g protein-coupled receptor repertoire of gastric ghrelin cells[j]. molecular metabolism, 2013, 2(4): 376-392. |
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