6-amino-1,3-dimethyl-4-(4-(trifluoromethyl)phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile Property

Boiling point:

493.4±45.0 °C(Predicted)

Density 

1.43±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

insoluble in H2O; ≥16.55 mg/mL in DMSO; ≥9.2 mg/mL in EtOH

form 

solid

pka

2.92±0.40(Predicted)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H312Harmful in contact with skin

H315Causes skin irritation

H319Causes serious eye irritation

H332Harmful if inhaled

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

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

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P321Specific treatment (see … on this label).

P322Specific measures (see …on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P363Wash contaminated clothing before reuse.

P501Dispose of contents/container to..…

6-amino-1,3-dimethyl-4-(4-(trifluoromethyl)phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile Chemical Properties,Usage,Production

Uses

BQU57 ia a novel blocker of Ral function.

Biological Activity

bqu57 is a derivative of rbc8. it show selectivity for ral relative to the gtpases ras and rhoa and inhibit tumour xenograft growth. the binding of bqu57 to ralb–gdp was with a dissociation constant (kd) of 7.760.6 mm by using isothermal titration calorimetry (itc). it was similar to the results from surface plasmon resonance (spr), which had a kd value of 4.761.5 mm 1.rbc8 or bqu57 can effectively inhibited the colony formation in soft agar of the ral-dependent lines h2122 and h358, but not h460 or calu-6. the ic50 value of rbc8 was 3.5 mm in h2122 cells and 3.4 mm in h358 cells; and the ic50 value of bqu57 was 2.0 mm in h2122 cells and 1.3 mm in h358 cells. rbc8 or bqu57 treatment showed no further inhibition of colony formation after ral knockdown 1.rbc8 and bqu57 acted specifically through the gdp-bound form of ral proteins. rbc8 and bqu57 inhibited both ral a and ral b activation in both the h2122 and h358 cell lines by a ral pull-down assay using ralbp1-bound agarose beads 1.the inhibition of ral activity and tumour growth by these compounds were evaluated in human lung cancer xenografts in mice. rbc8 and bqu57 showed good properties in vivo. rbc8 and bqu57 entry into tumour tissue 3 h after dosing, and were detectable in tumour tissue 1. bqu57 (10, 20 and 50mg per kg bodyweight) was intraperitoneal injected into h2122 tumour xenografts, and the activation of ral in tumour extracts was analysed in ralbp1 pull-down assays. both rala and ralb were inhibited by rbc8 and bqu57. but no inhibition of ras or rhoa activity was happened 1.

References

1. yan c, liu d, li l et al. discovery and characterization of small molecules that target the gtpase ral. nature. 2014 nov 20;515(7527):443-7.