ritlecitinib   Click here for help

GtoPdb Ligand ID: 9559

Synonyms: compound 11 [PMID: 28139931] | example 5 [WO2015083028] | PF-06651600 | PF06651600
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Ritlecitinib (PF-06651600) is a potent, orally active, selective covalent inhibitor of Janus kinase 3 (JAK3) [5], with anti-inflammatory activity in in vivo models [4]. It is example 5 in a Pfizer patent that provides SAR for 343 analogues [1]. There are three crystal structures available for compounds reported in [5] with JAK3, but not for compound 11 (the PDB identifiers are 5TTV, 5TTU and 5TTS). Pfizer's pipeline webpage indicates that the ritlecitinib program has been discontinued.
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 73.91
Molecular weight 285.16
XLogP 1.92
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help
Canonical SMILES C=CC(=O)N1CC(CCC1C)Nc1ncnc2c1cc[nH]2
Isomeric SMILES C=CC(=O)N1C[C@@H](CC[C@@H]1C)Nc1ncnc2c1cc[nH]2
InChI InChI=1S/C15H19N5O/c1-3-13(21)20-8-11(5-4-10(20)2)19-15-12-6-7-16-14(12)17-9-18-15/h3,6-7,9-11H,1,4-5,8H2,2H3,(H2,16,17,18,19)/t10-,11+/m0/s1
InChI Key CBRJPFGIXUFMTM-WDEREUQCSA-N
References
1. Brown MF, Casimiro-Garcia A, Che Y, Coe JW, Flanagen ME, Gilbert AM, Hayward MM, Langille JD, Montgomery JI, Telliez J-B et al.. (2015)
Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides.
Patent number: WO2015083028. Assignee: Pfizer Inc.. Priority date: 05/12/2013. Publication date: 11/06/2015.
2. King B, Guttman-Yassky E, Peeva E, Banerjee A, Sinclair R, Pavel AB, Zhu L, Cox LA, Craiglow B, Chen L et al.. (2021)
A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results.
J Am Acad Dermatol, 85 (2): 379-387. [PMID:33757798]
3. Robinson MF, Damjanov N, Stamenkovic B, Radunovic G, Kivitz A, Cox L, Manukyan Z, Banfield C, Saunders M, Chandra D et al.. (2020)
Efficacy and Safety of PF-06651600 (Ritlecitinib), a Novel JAK3/TEC Inhibitor, in Patients With Moderate-to-Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate.
Arthritis Rheumatol, 72 (10): 1621-1631. [PMID:32419304]
4. Telliez JB, Dowty ME, Wang L, Jussif J, Lin T, Li L, Moy E, Balbo P, Li W, Zhao Y et al.. (2016)
Discovery of a JAK3-Selective Inhibitor: Functional Differentiation of JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition.
ACS Chem Biol, 11 (12): 3442-3451. [PMID:27791347]
5. Thorarensen A, Dowty ME, Banker ME, Juba B, Jussif J, Lin T, Vincent F, Czerwinski RM, Casimiro-Garcia A, Unwalla R et al.. (2017)
Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans.
J Med Chem, 60 (5): 1971-1993. [PMID:28139931]