Leniolisib manufacturers
- Leniolisib
-
- $72.00
-
2026-05-11
- CAS:1354690-24-6
- Purity: 99.97%
- Supply Ability: 10g
|
| | Leniolisib Basic information |
| Product Name: | Leniolisib | | Synonyms: | Leniolisib;CDZ173;CDZ-173;CDZ 173;CS-2818;leniolisib(CDZ 173);1-Propanone, 1-[(3S)-3-[[5,6,7,8-tetrahydro-6-[6-methoxy-5-(trifluoromethyl)-3-pyridinyl]pyrido[4,3-d]pyrimidin-4-yl]amino]-1-pyrrolidinyl]-;(S)-1-(3-((6-(6-Methoxy-5-(trifluoromethyl)pyridin-3-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)propan-1-one;inhibit,Inhibitor,Phosphoinositide 3-kinase,Leniolisib,PI3K,CDZ-173,CDZ 173;Rupatadine Impurity 2-d8 | | CAS: | 1354690-24-6 | | MF: | C21H25F3N6O2 | | MW: | 450.46 | | EINECS: | | | Product Categories: | | | Mol File: | 1354690-24-6.mol |  |
| | Leniolisib Chemical Properties |
| storage temp. | Store at -20°C | | solubility | DMF:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);1.11(Max Conc. mM)
DMSO:71.67(Max Conc. mg/mL);159.09(Max Conc. mM)
Ethanol:16.5(Max Conc. mg/mL);36.63(Max Conc. mM) | | form | A crystalline solid | | color | White to off-white |
| | Leniolisib Usage And Synthesis |
| Uses | Leniolisib (CDZ173) is a potent and selective PI3Kδ inhibitor. Leniolisib has the potential for immunodeficiency disorders treatment. | | Biological Activity | Leniolisib (CDZ 173) is a potent and selective PI3Kδ inhibitor with IC50s of 0.244, 0.424, 2.23 and 0.011 μM for PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ, respectively. | | Synthesis |
The synthesis of leniolisib starts with compound 1 as shown in Scheme 1 (Hoegenauer et al., 2016; Hoegenauer et al., 2017).
6-Benzyl-4-chloro-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (compound 1) is coupled with (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (compound 2) in the presence of triethylamine at 120 °C for 42 h to give compound 3 a 93% yield. The benzyl group is deprotected with 20% palladium hydroxide on carbon and ammonium formate in methanol at 65 °C for 2 h to give compound 4 a 66% yield. Compound 4 is coupled with 5-bromo-2-methoxy-3-(trifluoromethyl)pyridine (compound 5) in the presence of sodium -tert-butoxide, tris(dibenzylideneacetone)dipalladium(0), 2-di-t-butylphosphino-2'-(N,N-dimethylamino)biphenyl in tert-butanol at 100 °C for 5 h to give compound 6 a 74% yield. Deprotection of the Boc group in DCM/TFA, followed by coupling with propionyl chloride in the presence of sodium bicarbonate in DCM at room temperature for 1 h gives the final compound 7 (leniolisib) a 76% yield.
| | in vivo | Oral leniolisib lead to a dose-dependent reduction in PI3K/AKT pathway activity and resolve the immune dysregulation with normalization of circulating transitional and nave B cells and reduction in PD-1+CD4+ and senescent CD57+CD8+ T cells. After 12 weeks of treatment, all patients show amelioration of lymphoproliferation with lymph node sizes and spleen volumes reduced by 39% (mean, range 26-57%) and 40% (mean, range: 13-65%), respectively[1]. | | target | | Target | Value | PI3Kδ
(Cell-free assay) | 0.011 μM | PI3Kα
(Cell-free assay) | 0.244 μM | < td style="border-bottom: 1px dotted #ccc;padding: 5px;"> PI3Kβ
(Cell-free assay) 0.424 μM | DNA-PK
() | 0.88 μM | DNA-PK
(Cell-free assay) | 0.88 μM |
| | IC 50 | PI3Kδ: 11 nM (IC50); PI3Kα: 280 nM (IC50); PI3Kβ: 480 nM (IC50); PI3Kγ: 2.57 μM (IC50); DNA-PK: 880 nM (IC50) | | References | [1] Rao V, et al. Effective 'Activated PI3Kd Syndrome' -targeted therapy with PI3Kd inhibitor leniolisib. The New England journal of medicine: NEJM. ISSN 0028-4793; 1533-4406 DOI:10.1182/blood-2017-08-801191
[2] Hoegenauer K, et al. Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors. ACS Med Chem Lett. 2017 Aug 25;8(9):975-980. DOI:10.1021/acsmedchemlett.7b00293 |
| | Leniolisib Preparation Products And Raw materials |
| Raw materials | 1-Pyrrolidinecarboxylic acid, 3-[[5,6,7,8-tetrahydro-6-[6-methoxy-5-(trifluoromethyl)-3-pyridinyl]pyrido[4,3-d]pyrimidin-4-yl]amino]-, 1,1-dimethylethyl ester, (3S)--->1-Pyrrolidinecarboxylic acid, 3-[[5,6,7,8-tetrahydro-6-(phenylmethyl)pyrido[4,3-d]pyrimidin-4-yl]amino]-, 1,1-dimethylethyl ester, (3S)--->1-Pyrrolidinecarboxylic acid, 3-[(5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)amino]-, 1,1-dimethylethyl ester, (3S)--->6-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-->5-bromo-2-methoxy-3-(trifluoromethyl)pyridine-->2-Methoxy-3-(trifluoromethyl)pyridine-->(S)-(-)-1-tert-Butoxycarbonyl-3-aminopyrrolidine-->2-Chloro-3-(trifluoromethyl)pyridine-->Propionyl chloride |
|