R1487 free base | CAS#449811-92-1 | p38α inhibitor

MedKoo Cat#: 555669 | Name: R1487 free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

R-1487 is an orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase. Pyruvate dehydrogenase (PDH) plays an important role in regulating carbohydrate oxidation in skeletal muscle. PDH is deactivated by a set of PDH kinases (PDK1, PDK2, PDK3, PDK4), with PDK2 and PDK4 being the most predominant isoforms in skeletal muscle.

Chemical Structure

R1487 free base

CAS#449811-92-1 (free base)

Theoretical Analysis

MedKoo Cat#: 555669

Name: R1487 free base

CAS#: 449811-92-1 (free base)

Chemical Formula: C19H18F2N4O3

Exact Mass: 388.1347

Molecular Weight: 388.37

Elemental Analysis: C, 58.76; H, 4.67; F, 9.78; N, 14.43; O, 12.36

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 weeks
100mg	USD 750.00	2 weeks
200mg	USD 1,250.00	2 weeks
500mg	USD 2,850.00	2 weeks
1g	USD 3,950.00	2 weeks
2g	USD 6,450.00	2 weeks

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Related CAS #

449811-92-1 (free base) 449808-64-4 (HCl)

Synonym

R-1487; R 1487; R1487;

IUPAC/Chemical Name

6-(2,4-Difluorophenoxy)-8-methyl-2-(tetrahydropyran-4-ylamino)pyrido(2,3-d)pyrimidin-7-one

InChi Key

KKKRKRMVJRHDMG-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H18F2N4O3/c1-25-17-11(10-22-19(24-17)23-13-4-6-27-7-5-13)8-16(18(25)26)28-15-3-2-12(20)9-14(15)21/h2-3,8-10,13H,4-7H2,1H3,(H,22,23,24)

SMILES Code

O=C1C(OC2=CC=C(F)C=C2F)=CC3=CN=C(NC4CCOCC4)N=C3N1C

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMF

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMF

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

R1487 is an orally bioavailable and highly selective inhibitor of p38α with an ic50 value of 10 nM.

In vitro activity:

To be determined

In vivo activity:

The development of a new series of p38α inhibitors (one compound being R1487) resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. Reference: . J Med Chem. 2011 Apr 14;54(7):2255-65. https://pubmed.ncbi.nlm.nih.gov/21375264/

	Solvent	mg/mL	mM
Solubility
	DMF	42.0	98.86

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 388.37 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Goldstein DM, Soth M, Gabriel T, Dewdney N, Kuglstatter A, Arzeno H, Chen J, Bingenheimer W, Dalrymple SA, Dunn J, Farrell R, Frauchiger S, La Fargue J, Ghate M, Graves B, Hill RJ, Li F, Litman R, Loe B, McIntosh J, McWeeney D, Papp E, Park J, Reese HF, Roberts RT, Rotstein D, San Pablo B, Sarma K, Stahl M, Sung ML, Suttman RT, Sjogren EB, Tan Y, Trejo A, Welch M, Weller P, Wong BR, Zecic H. Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase. J Med Chem. 2011 Apr 14;54(7):2255-65. doi: 10.1021/jm101423y. Epub 2011 Mar 4. PMID: 21375264.

In vitro protocol:

To be determined

In vivo protocol:

1: Hashimoto T, Kondo N, Makino A, Kiyono Y, Temma T. Radiobrominated probe targeting activated p38α in inflammatory diseases. Ann Nucl Med. 2022 Oct;36(10):845-852. doi: 10.1007/s12149-022-01764-2. Epub 2022 Jun 27. PMID: 35760973. 2: Royle SR, Young JJ. Developmental biology: A 5'Hoxd-Gli3 balance in tetrapod axial polarity. Curr Biol. 2021 Nov 22;31(22):R1487-R1490. doi: 10.1016/j.cub.2021.10.031. PMID: 34813756. 3: Hashimoto T, Kondo N, Hirata M, Temma T. Development of radioiodinated pyrimidinopyridone derivatives as targeted imaging probes of activated p38α for single photon emission computed tomography. Ann Nucl Med. 2021 Dec;35(12):1293-1304. doi: 10.1007/s12149-021-01669-6. Epub 2021 Aug 19. PMID: 34410619. 4: Dunford EC, Herbst EA, Jeoung NH, Gittings W, Inglis JG, Vandenboom R, LeBlanc PJ, Harris RA, Peters SJ. PDH activation during in vitro muscle contractions in PDH kinase 2 knockout mice: effect of PDH kinase 1 compensation. Am J Physiol Regul Integr Comp Physiol. 2011 Jun;300(6):R1487-93. doi: 10.1152/ajpregu.00498.2010. Epub 2011 Mar 16. PMID: 21411764. 5: Goldstein DM, Soth M, Gabriel T, Dewdney N, Kuglstatter A, Arzeno H, Chen J, Bingenheimer W, Dalrymple SA, Dunn J, Farrell R, Frauchiger S, La Fargue J, Ghate M, Graves B, Hill RJ, Li F, Litman R, Loe B, McIntosh J, McWeeney D, Papp E, Park J, Reese HF, Roberts RT, Rotstein D, San Pablo B, Sarma K, Stahl M, Sung ML, Suttman RT, Sjogren EB, Tan Y, Trejo A, Welch M, Weller P, Wong BR, Zecic H. Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino] -8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy )-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen- activated protein kinase. J Med Chem. 2011 Apr 14;54(7):2255-65. doi: 10.1021/jm101423y. Epub 2011 Mar 4. PMID: 21375264.