[CAS NO. 862309-06-6] MK-0249

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PRODUCTS SPECIFICATIONS [862309-06-6]

Catalog

HY-U00076

Brand

MCE

CAS

862309-06-6

DESCRIPTION [862309-06-6]

Overview

MDL	-
Molecular Weight	431.45
Molecular Formula	C₂₃H₂₄F₃N₃O₂
SMILES	-

For research use only. We do not sell to patients.

Summary

MK-0249 (Compound 1) is a potent, selective and orally active histamine H ₃ receptor antagonist, with an IC ₅₀ of 1.7 nM for human H3 ^[1] .

IC50 & Target

human H ₃ receptor

1.7 nM (IC ₅₀ )

rhesus H ₃ receptor

4.3 nM (Ki)

human H ₃ receptor

6.8 nM (Ki)

rat H ₃ receptor

33 nM (Ki)

In Vitro

MK-0249 (Compound 1) shows very good hepatic clearance values (CLh e 11 mL/min/kg), and is a substrate for rat P-gp but not for human P-gp ^[1] .
MK-0249 displays potent binding affinity to human, rat, and rhesus H ₃ receptors with K _i values of 6.8 ± 1.3 nM, 33 ± 3 nM, and 4.3 ± 1.2 nM, respectively ^[1] .
MK-0249 shows high intrinsic activity ^[1] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

MK-0249 (Compound 1) (0-30 mg/kg; p.o.; once) elevates histamine levels in the rat brain in a dose-dependent manner ^[1] .
MK-0249 (10 mg/kg; p.o.; once) shows markedly higher brain penetrability and a lower plasma Occ90 value in mdr1a (-/-) mice than in mdr1a (+/+) mice ^[1] .
MK-0249 shows rodent brain permeability and is significantly limited by P-gp mediated efflux in rodents, whereas the extent of P-gp mediated efflux in humans should be very small or negligible ^[1] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	SD rats ^[1]
Dosage:	3, 10 and 30 mg/kg
Administration:	Oral administration, once
Result:	Showed a statistically significant increase in tele-methylhistamine levels at 30 mg/kg.

Animal Model:	P-gp-deficient mdr1a (-/-) and wild type mdr1a (+/+) CF-1 mice ^[1]
Dosage:	10 mg/kg
Administration:	Oral administration, once
Result:	The brain-to-plasma ratio in mdr1a (-/-) mice (b/p = 14) was remarkably higher than that in SD rats (b/p = 1.1) and mdr1a (+/+) mice (b/p = 0.8).

Animal Model:

Male Sprague-Dawley rats, male Beagle dogs, and male rhesus monkeys ^[1]

Dosage:

1 or 3 mg/kg

Administration:

IV or PO (Pharmacokinetic Analysis)

Result:

Pharmacokinetic Parameters of 1 in Rats, Dogs, and Rhesus Monkeys ^a ^[1]

iv (1 mg/kg)

po (3 mg/kg)

CL _p
(mL/min/kg)

V _dss
(L/kg)

t _1/2
(h)

C _max
(µM)

AUC _0-∞
(µM h)

F ^b
(%)

rat

4.4

5.5

1.01

6.35

dog

9.7

9.9

1.8

11.8

>100

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase
NCT00620659	Merck Sharp & Dohme LLC	Sleep Apnea, Obstructive\|Hypopnea Syndrome\|Excessive Daytime Sleepiness	February 2008	Phase 2
NCT00420420	Merck Sharp & Dohme LLC	Alzheimer´s Disease	November 2006	Phase 2
NCT00506077	Merck Sharp & Dohme LLC	Paranoid Schizophrenia	December 2007	Phase 2
NCT00874939	Merck Sharp & Dohme LLC	Alzheimer´s Disease\|Dementia	April 6, 2009	Phase 1
NCT00475735	Merck Sharp & Dohme LLC	Attention-Deficit+Hyperactivity Disorder (ADHD)	July 2007	Phase 2

Molecular Weight

431.45

Appearance

Solid

Formula

C ₂₃ H ₂₄ F ₃ N ₃ O ₂

CAS No.

862309-06-6

SMILES

O=C1N(C2=CC=C(OCCCN3CCCC3)C=C2)C(C)=NC4=C1C(C(F)(F)F)=CC=C4

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : 50 mg/mL ( 115.89 mM ; Need ultrasonic)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.3178 mL	11.5888 mL	23.1777 mL
5 mM	0.4636 mL	2.3178 mL	4.6355 mL
10 mM	0.2318 mL	1.1589 mL	2.3178 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline

Solubility: ≥ 1.25 mg/mL (2.90 mM); Clear solution
2.

Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)

Solubility: ≥ 1.25 mg/mL (2.90 mM); Clear solution
3.

Add each solvent one by one: 10% DMSO >> 90% corn oil

Solubility: ≥ 1.25 mg/mL (2.90 mM); Clear solution