Milciclib

Base Information

• Chemical Name: Milciclib
• CAS No.: 802539-81-7
• Molecular Formula: C₂₅H₃₂N₈O
• Molecular Weight: 460.582
• UNII: 688000M8S8
• ChEMBL ID: CHEMBL564829
• DSSTox Substance ID: DTXSID80230186
• NCI Thesaurus Code: C148410
• Pharos Ligand ID: F18LUCB1FLDK
• Wikidata: Q27086363
• Mol file: 802539-81-7.mol

Synonyms:miliciclib;N,1,4,4-tetramethyl-8-((4-(4-methylpiperazin-1-yl)phenyl)amino)-4,5-dihydro-1H-pyrazolo(4,3-h)quinazoline-3-carboxamide;PHA 848125;PHA-848125;PHA-848125AC;PHA848125

Chemical Property of Milciclib

Chemical Property:

• Melting Point: 190 °C
• PKA: 14.44±0.40(Predicted)
• PSA: 94.70000
• Density: 1.33 g/cm³
• LogP: 3.21650
• Solubility.: ≥23.05 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
• XLogP3: 2.8
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 4
• Exact Mass: 460.26990767
• Heavy Atom Count: 34
• Complexity: 718

Purity/Quality:

99% ^*data from raw suppliers

PHA-848125 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1(CC2=CN=C(N=C2C3=C1C(=NN3C)C(=O)NC)NC4=CC=C(C=C4)N5CCN(CC5)C)C
• Recent EU Clinical Trials: Phase IIA Exploratory Study of Oral Milciclib Maleate in Patients with Unresectable or Metastatic Hepatocellular Carcinoma
• Description: PHA-848125 is an ATP-competitive inhibitor of cyclin-dependent kinases (Cdks) that potently inhibits Cdk2/cyclin A (IC50 = 45 nM). It is at least 3-fold less potent at Cdks 1, 3, 4, 5, and 7. PHA-848125 is orally available and displays efficacy in suppressing the growth of cancer cells or tumor xenografts in animals.
• Uses: PHA-848125 is a cyclin dependent kinase (CDK) inhibitor. Oral PHA-848125 showed antitumor activity via dual targeting of cyclin-dependent kinase and tropomyosin receptor kinase families in human carcinoma cell and xenografted mouse model of carcinoma.

Technology Process of Milciclib

There total 5 articles about Milciclib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 92.0%

8-[4-(4-methyl-piperazin-1-yl)phenylamino]-1,4,4-trimethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid potassium salt + methylamine (74-89-5) → PHA-848125 (802539-81-7)

Guidance literature:

With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; DMF (N,N-dimethyl-formamide); at 20 ℃; for 18h;

Reference yield: 65.0%

8-iodo-N,1,4,4-tetramethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide + 4-(4-Methyl-piperazino)-anilin (16153-81-4) → PHA-848125 (802539-81-7)

Guidance literature:

With palladium diacetate; potassium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 80 ℃; for 3h; Inert atmosphere;

DOI:10.1021/jm9006559

Reference yield:

4-(4-Methyl-piperazino)-anilin (16153-81-4) → PHA-848125 (802539-81-7)

Guidance literature:

Multi-step reaction with 3 steps

1: potassium carbonate / palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / DMF (N,N-dimethyl-formamide) / 4 h / 20 - 80 °C

2: potassium hydroxide / ethanol / 3 h / Heating / reflux

3: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran; DMF (N,N-dimethyl-formamide) / 18 h / 20 °C

With potassium hydroxide; potassium carbonate; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In tetrahydrofuran; DMF (N,N-dimethyl-formamide); ethanol;

upstream raw materials:

methylamine

4-(4-Methyl-piperazino)-anilin

Downstream raw materials:

8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-1,4,4-trimethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid methylamide glycolate

Refernces

• 1、 -. "PYRAZOLO-QUINAZOLINE DERIVATIVES,PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS". Page 179-180; 187. . Retrieved 2008/06/13.