ritlecitinib   

GtoPdb Ligand ID: 9559

Synonyms: compound 11 [PMID: 28139931] | example 5 [WO2015083028] | PF-06651600 | PF06651600
Compound class: Synthetic organic
Comment: Ritlecitinib (PF-06651600) is a potent, orally active, selective covalent inhibitor of Janus kinase 3 (JAK3) [3], with anti-inflammatory activity in in vivo models [2]. 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 [3] with JAK3, but not for compound 11 (the PDB identifiers are 5TTV, 5TTU and 5TTS).
2D Structure
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Physico-chemical Properties
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
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. 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]
3. 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]