924641-59-8

Basic information

• Product Name: [4-[[5-Fluoro-4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-2-pyrimidinyl]amino]phenyl][(3S)-3-(methylamino)-1-pyrrolidinyl]Methanone
• Synonyms: [4-[[5-Fluoro-4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-2-pyrimidinyl]amino]phenyl][(3S)-3-(methylamino)-1-pyrrolidinyl]Methanone;AZD 5597;(S)-(4-((5-Fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidin-2-yl)amino)phenyl)(3-(methyl;(S)-(4-((5-Fluoro-4-(1-isopropyl-2-Methyl-1H-iMidazol-5-yl)pyriMidin-2-yl)aMino)phenyl)(3-(MethylaMino)pyrrolidin-1-yl)Methanone;(3-(methylamino);-(4-((5-Fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl);pyrimidin-2-yl);(S)-(4-((5-Fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidin-2-yl)amino)phenyl)(3-(met
• CAS NO: 924641-59-8
• Molecular Formula: C23H28FN7O
• Molecular Weight: 437.52
• Mol File: 924641-59-8.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 679.0±65.0 °C(Predicted)
• Appearance: /
• Density: 1.32
• Storage Temp.: 2-8°C(protect from light)
• Solubility: ≥1.82 mg/mL in H2O with ultrasonic; ≥12.7 mg/mL in EtOH; ≥15.65 mg/mL in DMSO
• PKA: 9.66±0.20(Predicted)
• CAS DataBase Reference: [4-[[5-Fluoro-4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-2-pyrimidinyl]amino]phenyl][(3S)-3-(methylamino)-1-pyrrolidinyl]Methanone(CAS DataBase Reference)
• NIST Chemistry Reference: [4-[[5-Fluoro-4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-2-pyrimidinyl]amino]phenyl][(3S)-3-(methylamino)-1-pyrrolidinyl]Methanone(924641-59-8)
• EPA Substance Registry System: [4-[[5-Fluoro-4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-2-pyrimidinyl]amino]phenyl][(3S)-3-(methylamino)-1-pyrrolidinyl]Methanone(924641-59-8)

Safety Data

• Hazardous Substances Data: 924641-59-8(Hazardous Substances Data)

Usage

Biological Activity

azd-5597 is a potent cdk inhibitor with ic50 values of 2 nm for cdk1 and cdk2, respectively [1].the cyclin-dependent kinases (cdks) are serine-threonine protein kinases with roles in the regulation of the cell cycle, and also involved in regulating transcription, mrna processing, and the differentiation of nerve cells [1].azd-5597 is a potent imidazole pyrimidine amide cdk inhibitor. in lovo cells, azd-5597 exhibited high level of anti-proliferative activity with ic50 value of 0.039 μm. azd-5597 exhibited excellent aqueous solubility ( > 50 mg/ml), photostability (t1/2 > 24 h), hydrolytic stability (ph 4-10, t1/2 > 100 days), plasma stability ( > 18 h) and the lack of cyp inhibition. the overall profile of azd-5597 indicated that it was suitable for further development as an iv agent [1].in nude mouse and rat, azd-5597 possessed good pharmacokinetic parameters with moderate to low clearance. in nude mice implanted subcutaneously with sw620 human colon adenocarcinoma cells, azd-5597 (15 mg/kg, dosed intermittently for 3 weeks, ip) inhibited tumour volume by 55% [1].

references

jones cd, andrews dm, barker aj, et al. the discovery of azd5597, a potent imidazole pyrimidine amide cdk inhibitor suitable for intravenous dosing. bioorganic & medicinal chemistry letters, 2008, 18(24): 6369-6373.

Upstream product

• 893420-22-9 5-fluoro-4-(2-methyl-3-(propan-2-yl)-3H-imidazol-4-yl)pyrimidin-2-amine 
• 924643-04-9 [(3S)-3-(methylamino)pyrrolidin-1-yl]-(4-iodophenyl)methanone 

Relevant articles and documents

The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing

The development of a novel series of imidazole pyrimidine amides as cyclin-dependent kinase (CDK) inhibitors is described. Optimisation of inhibitory potency against multiple CDK's (1, 2 and 9) resulted in imidazole pyrimidine amides with potent in vitro anti-proliferative effects against a range of cancer cell lines. Excellent physiochemical properties and large margins against inhibition of CYP isoforms and the hERG ion channel were achieved by modification of lipophilicity and amine basicity. A candidate with disease model activity in human cancer cell line xenografts and with suitable physiochemical and pharmacokinetic profiles for intravenous (iv) dosing was selected for further development as AZD5597.