SB-206606

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H22ClNO4
Molecular Weight	363.835
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H](CC1=CC=C(OCC(O)=O)C=C1)NC[C@H](O)C2=CC(Cl)=CC=C2

InChI

InChIKey=ZGGNJJJYUVRADP-ACJLOTCBSA-N

InChI=1S/C19H22ClNO4/c1-13(21-11-18(22)15-3-2-4-16(20)10-15)9-14-5-7-17(8-6-14)25-12-19(23)24/h2-8,10,13,18,21-22H,9,11-12H2,1H3,(H,23,24)/t13-,18+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C19H22ClNO4
Molecular Weight	363.835
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15684518 | https://www.rndsystems.com/products/brl-37344-sodium-salt_0948 | https://www.ncbi.nlm.nih.gov/pubmed/23955701 | https://www.ncbi.nlm.nih.gov/pubmed/25462854 | https://www.ncbi.nlm.nih.gov/pubmed/1345889 |https://www.ncbi.nlm.nih.gov/pubmed/23890664 | http://adisinsight.springer.com/drugs/800006890 | https://www.ncbi.nlm.nih.gov/pubmed/12237641 | https://www.ncbi.nlm.nih.gov/pubmed/8773403 | https://www.ncbi.nlm.nih.gov/pubmed/20930473

BRL-37344 is a selective β3-adrenergic receptor agonist originated by GlaxoSmithKline. Ki value is 287 nM for β3 receptor, 1750 nM for β1 receptor and 1120 nM for β2 receptor. BRL-37344 can decrease nerve-evoked contractions in human detrusor smooth muscle isolated strips, it can also stimulate fuel oxidation by soleus muscle in vitro. In fasted rabbits, BRL-37344 significantly increased plasma nonesterified fatty acids (NEFA) levels through β3-adrenoceptor. However, BRL-37344 had no effect on plasma glucose levels. In mice, BRL-37344 increased circulating transaminase levels through activation of β3-adrenoceptor. BRL-37344 increases glucose transport into L6 myocytes through a mechanism different from that of insulin. But preclinical for Diabetes mellitus was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-3 adrenergic receptor 49 Target ID: CHEMBL246 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8719421 \| https://www.ncbi.nlm.nih.gov/pubmed/7912272 \| https://www.ncbi.nlm.nih.gov/pubmed/14730417 \| https://www.ncbi.nlm.nih.gov/pubmed/12237641	Agonist 2678		430.0 nM [Ki]
Beta-3 adrenergic receptor 49 Target ID: P13945 Gene ID: 155.0 Gene Symbol: ADRB3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15684518	Agonist 2678		17.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Diabetes mellitus 91 Sources: http://adisinsight.springer.com/drugs/800006890 https://www.ncbi.nlm.nih.gov/pubmed/8696421	Primary	Preclinical	Unknown Approved Use Unknown
Diabetes mellitus 91 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1345889	Primary	Preclinical	Unknown Approved Use Unknown
Alcoholism 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23955701	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Atypical beta-adrenergic receptor in 3T3-F442A adipocytes. Pharmacological and molecular relationship with the human beta 3-adrenergic receptor.	1991 Oct 25	1682311
Effects of beta-adrenoceptor subtype stimulation on obese gene messenger ribonucleic acid and on leptin secretion in mouse brown adipocytes differentiated in culture.	1997 Feb	9002984
Adrenergic stimulation of lipoprotein lipase gene expression in rat brown adipocytes differentiated in culture: mediation via beta3- and alpha1-adrenergic receptors.	1997 Feb 1	9032464
Selective activation of beta3-adrenoceptors by octopamine: comparative studies in mammalian fat cells.	1999 Apr	10344530
beta1 to beta3 switch in control of cyclic adenosine monophosphate during brown adipocyte development explains distinct beta-adrenoceptor subtype mediation of proliferation and differentiation.	1999 Sep	10465291
Norepinephrine induces vascular endothelial growth factor gene expression in brown adipocytes through a beta -adrenoreceptor/cAMP/protein kinase A pathway involving Src but independently of Erk1/2.	2000 May 5	10788502
5-HT(7) receptor and beta(2)-adrenoceptor share in the inhibition of porcine uterine contractility in a muscle layer-dependent manner.	2001 Dec 21	11755152
Enhancement of memory consolidation in chicks by beta(3)-adrenoceptor agonists.	2001 Feb 16	11226398
Beta2-adrenoceptor-mediated inhibition of field stimulation induced contractile responses of the smooth muscle of the rat prostate gland.	2001 Nov 9	11716846
Metabolic markers following beta-adrenoceptor agonist infusion in footshock-stressed rats.	2001 Sep	11514845
Comparative pharmacology of human beta-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cells.	2004 Feb	14730417
[Effect of beta3-adrenoreceptors agonist on beta3-adrenoreceptors expression and myocyte apoptosis in a rat model of heart failure].	2004 Mar	15009959
Induction of beta3-adrenergic receptor functional expression following chronic stimulation with noradrenaline in neonatal rat cardiomyocytes.	2006 Jan	16183708
Role of beta-3-adrenoceptor in catecholamine-induced relaxations in gastric fundus from control and diabetic rats.	2007	17622774
The effects and selectivity of beta-adrenoceptor agonists in rat myometrium and urinary bladder.	2007 Nov 14	17632099
Metabolic responses to BRL37344 and clenbuterol in soleus muscle and C2C12 cells via different atypical pharmacologies and beta2-adrenoceptor mechanisms.	2008 Oct	18552870
β3-adrenoceptor-mediated increased circulating transaminase levels in mice treated with its agonist BRL 37344.	2010 Oct	20930473

Patents

Sample Use Guides

In Vivo Use Guide

The effect of SB-206606 on the liver uptake of Brown Adipose Tissue in the Liver (BAT/L) was examined in mice. Obese mice and mice with Diabetes Mellitus (DM) received an intraperitoneal injection of SB-206606 (2.5 mg/kg) three times per week for two weeks. After two weeks of treatment with SB-206606, there was a significant increase in BAT/L for both obese mice (6.64±1.97) and DM mice (5.25±1.50) compared with the controls without SB-206606 treatment (4.20±1.13 in obese control mice, P = 0.010; 2.32±1.01 in DM control mice, P = 0.004). In normal control mice, even a single-dose of SB-206606 would significantly increase BAT/L compared with the untreated controls (31.74±21.39 versus 7.61±1.44, P = 0.002).

Route of Administration: Intraperitoneal

In Vitro Use Guide

Human B3-AR cDNA was cloned from total RNA extracted from human neuroblastoma cell SK-N-MC (ATCC HTB 10), and inserted into a pKCN1 plasmid, which was subsequently transformed into Chinese Hamster Ovary Cell line (CHO-K1). B3-AR agonistic activity was assessed by measurement of cAMP accumulation level in CHO cells expressing human b3-AR. Cells were treated with varying concentrations of SB-206606 and the EC50 value was determined as the concentration required to achieve 50% of cAMP accumulation. BRL 37344 exhibited agonistic activity with EC50 17 nM.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:48:44 GMT 2023` Edited by `admin` on `Sat Dec 16 10:48:44 GMT 2023`
Record UNII	42FZ27IZLV
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SB-206606

Common Name

English

ACETIC ACID, 2-(4-((2R)-2-(((2R)-2-(3-CHLOROPHENYL)-2-HYDROXYETHYL)AMINO)PROPYL)PHENOXY)-

Common Name

English

BRL-44092

Common Name

English

(4-((2R)-2-(((2R)-2-(3-CHLOROPHENYL)-2-HYDROXYETHYL)AMINO)PROPYL)PHENOXY)ACETIC ACID

Systematic Name

English

2-(4-((2R)-2-(((2R)-2-(3-CHLOROPHENYL)-2-HYDROXYETHYL)AMINO)PROPYL)PHENOXY)ACETIC ACID

Systematic Name

English

ACETIC ACID, (4-((2R)-2-(((2R)-2-(3-CHLOROPHENYL)-2-HYDROXYETHYL)AMINO)PROPYL)PHENOXY)-

Systematic Name

English

Code System Code Type Description

FDA UNII

42FZ27IZLV