924416-43-3

Basic information

• Product Name: SC-396658
• Synonyms: SC-396658;AdipoRon;2-(4-benzoylphenoxy)-N-(1-benzylpiperidin-4-yl)acetaMide;2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]acetamide;2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]acetamide AdipoRon;AdipoR agonist;AdipiRon
• CAS NO: 924416-43-3
• Molecular Formula: C₂₇H₂₈N₂O₃
• Molecular Weight: 428.52282
• Product Categories: Inhibitors
• Mol File: 924416-43-3.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 645.3±55.0 °C(Predicted)
• Appearance: white to beige/
• Density: 1.21±0.1 g/cm3(Predicted)
• Storage Temp.: room temp
• Solubility: DMSO: soluble10mg/mL, clear
• PKA: 13.92±0.20(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 2 months.
• CAS DataBase Reference: SC-396658(CAS DataBase Reference)
• NIST Chemistry Reference: SC-396658(924416-43-3)
• EPA Substance Registry System: SC-396658(924416-43-3)

Safety Data

• Hazard Codes: Xn,N
• Statements: 22-50/53
• Safety Statements: 60-61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 924416-43-3(Hazardous Substances Data)

Usage

Description

SC-396658 is an orally active small molecule AdipoR agonist that binds to adiponectin receptors AdipoR1 and AdipoR2 with KD values of 1.8 and 3.1 μM, respectively. It activates AMPK and PPARα pathways, exerting antidiabetic effects and reducing insulin resistance and glucose intolerance.

Uses

Used in Pharmaceutical Industry:
SC-396658 is used as a therapeutic approach for the treatment of obesity-related diseases such as type 2 diabetes. It activates AMPK and PPARα pathways, ameliorating diabetes and prolonging the lifespan of genetically obese db/db mice on a high-fat diet.

Biochem/physiol Actions

AdipoRon is an adiponectin agonist that binds to and activates adiponectin receptors AdipoR1 and AdipoR2, activating AMPK and PPAR-α pathways, and ameliorating insulin resistance and glucose intolerance in mice fed a high-fat diet in a manner similar to adiponectin itself. AdipoRon did not affect body weight, but did increase the expression of genes involved in fatty-acid oxidation, decreased tissue triglyceride content, and prolonged the shortened lifespan of db/db mice.

References

1) Okada-Iwabu?et al. (2013),?A small-molecule AdipoR agonist for type 2 diabetes and short life obesity; Nature 503?493 2) Fairaq?et al.?(2017),?AdipoRon, an adiponectin receptor agonist, attenuates PDGF-induced VSMC proliferation through inhibition of mTOR signaling independent of AMPK: Implications toward suppression of neointimal hyperplasia; Pharmacol. Res.?119?289

Synthetic route

4-amino-1-benzylpiperidine (50541-93-0) + 2-(4-benzoylphenoxy)-acetic acid (6322-83-4) → 2-(4-benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide (924416-43-3)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine	49%
Stage #1: 2-(4-benzoylphenoxy)-acetic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 60℃; for 3h; Stage #2: 4-amino-1-benzylpiperidine In N,N-dimethyl-formamide at 100℃; for 1h; Sealed tube;

4-Hydroxybenzophenone (1137-42-4) → 2-(4-benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide (924416-43-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium methylate / methanol 2: sodium hydroxide; water / methanol 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine View Scheme
Multi-step reaction with 3 steps 1.1: potassium carbonate / acetone / Reflux 2.1: sodium hydroxide / water 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 3 h / 60 °C 3.2: 1 h / 100 °C / Sealed tube View Scheme

methyl 2-(4-benzoylphenoxy)acetate (57682-09-4) → 2-(4-benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide (924416-43-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide; water / methanol 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydroxide / water 2.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 3 h / 60 °C 2.2: 1 h / 100 °C / Sealed tube View Scheme

2-(4-benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide (924416-43-3) → C27H27(2)HN2O3

Conditions	Yield
With water-d2 at 20℃; for 3h;

Upstream product

• 50541-93-0 4-amino-1-benzylpiperidine 
• 6322-83-4 2-(4-benzoylphenoxy)-acetic acid 
• 1137-42-4 4-Hydroxybenzophenone 
• 57682-09-4 methyl 2-(4-benzoylphenoxy)acetate 

Relevant articles and documents

ACTIVATOR OF ADIPONECTIN RECEPTOR

An AdipoR activator for activating both AdipoR1 and AdipoR2 is provided. A compound represented by the following formula (1), wherein A is a substituted or unsubstituted aryl group or the like, Y1 is (CHR2)a— or the like, X is CH or N, R1 is a C1-7 alkyl group, m is an integer of 0-4, Y2 is *—O—CH2—CONH—, *—CONH—(CH2)b—CO— or the like, Z is a cyclic group, B may be a substituent of the cyclic group represented by Z, and n is an integer of 0-3.