DB-07268 Property

Boiling point:

641.6±65.0 °C(Predicted)

Density 

1.427±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

insoluble in EtOH; insoluble in H2O; ≥15.2 mg/mL in DMSO

form 

solid

pka

9.66±0.10(Predicted)

color 

White to yellow

Safety

HS Code 

2933998090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

DB-07268 Chemical Properties,Usage,Production

Uses

2-[[2-[(3-Hydroxyphenyl)amino]-4-pyrimidinyl]amino]benzamide is an intermediate used in the preparation of pyrido-pyrimidinone derivatives with potential as an antidiabetic agent.

Definition

ChEBI: 2-({2-[(3-hydroxyphenyl)amino]pyrimidin-4-yl}amino)benzamide is an aminopyrimidine and a member of benzamides. It has a role as a protein kinase inhibitor.

Biological Activity

db07268 is a jnk1 inhibitor. the c-jun n-terminal kinases (jnks) are members of the mitogen-activated protein kinase family. three jnk isoforms (jnk1, 2 and 3) have been identified. there is growing evidences indicating that activation of the jnk activity is involved in a number of human disease settings. therefore, considerable efforts have been directed toward the identification of jnk inhibitors suitable for clinical development.

in vitro

the selectivity data of db07268 against a panel of kinases has been tested. results showed that db07268 had some degree of selectivity over quite a few kinases with the exceptions of plk, chk1, and ck2. although d db07268 showed submicromolar potency against these three kinases, it still appeared to exhibit at least 70- to 90-fold greater potency against jnk1 than plk, chk1, and ck2 [1].

in vivo

several analogs of db07268 were profiled in vivo. these compounds had a range of exposure in rats and mice. some had excellent brain penetration despite having poor rat pharmacokinetics, while others had a more balanced profile. unfortunately, the most potent analog exhibited poor rat pk demonstrated by a short half-life, low oral absorption and poor brain penetration. one db07268 analog likely exhibited modest rat pk with low clearance and decent oral absorption. this analog also showed modest brain penetration [1].

IC 50

9 nm for jnk1

References

[1] liu m,wang s,clampit je,gum rj,haasch dl,rondinone cm,trevillyan jm,abad-zapatero c,fry eh,sham hl,liu g. discovery of a new class of 4-anilinopyrimidines as potent c-jun n-terminal kinase inhibitors: synthesis and sar studies. bioorg med chem lett.2007 feb 1;17(3):668-72. epub 2006 nov 2.
[2] romain nol, youseung shin, xinyi song, yuanjun he, marcel koenig, weimin chen, yuan yuan ling, li lin, claudia h. ruiz, phil lograsso, michael d. cameron, derek r. duckett, theodore m. kamenecka. synthesis and sar of 4-(pyrazol-3-yl)-pyridines as novel c-jun n-terminal kinase inhibitors.bioorg med chem lett. 2011 may 1; 21(9): 2732–2735.