rodatristat   Click here for help

GtoPdb Ligand ID: 10647

Synonyms: compound 15a [PMID: 28041831] | KAR-5417 | KAR5417
PDB Ligand
Compound class: Synthetic organic
Comment: Rodatristat (KAR5417) inhibits both isoforms of L-Tryptophan hydroxylase (TPH) [2]. The TPH enzymes are responsible for biosynthesis of 5-HT. TPH1 is expressed by intestinal enterochromaffin cells where most peripheral 5-HT is formed, and THP2 is exclusively expressed in the CNS and generates 5-HT in the brain. Rodatristat acts as a serotonin synthesis inhibitor. As rodatristat cannot cross the blood-brain-barrier its activity is restricted to inhibition of peripherally expressed TPH1 and it should not produce the undesirable psychiatric side-effects that are known to result from any reduction in central 5-HT level.
Inhibition of serotonin synthesis is being actively pursued as a mechanistic approach for application to the treatment of the expansive range of diseases that have been associated with a dysfunctional peripheral serotonin system (carcinoid syndrome, gastro-intestinal diseases, fibrotic diseases, NAFLD, atherothrombotic diseases, pulmonary arterial hypertension and some cancers and immune diseases [1,3]).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 113.6
Molecular weight 561.18
XLogP 4.93
No. Lipinski's rules broken 0
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Canonical SMILES Nc1nc(cc(n1)N1CCC2(CC1)CN[C@@H](C2)C(=O)O)O[C@@H](C(F)(F)F)c1ccc(cc1c1ccccc1)Cl
Isomeric SMILES Nc1nc(cc(n1)N1CCC2(CC1)CN[C@@H](C2)C(=O)O)O[C@@H](C(F)(F)F)c1ccc(cc1c1ccccc1)Cl
InChI InChI=1S/C27H27ClF3N5O3/c28-17-6-7-18(19(12-17)16-4-2-1-3-5-16)23(27(29,30)31)39-22-13-21(34-25(32)35-22)36-10-8-26(9-11-36)14-20(24(37)38)33-15-26/h1-7,12-13,20,23,33H,8-11,14-15H2,(H,37,38)(H2,32,34,35)/t20-,23+/m0/s1
Classification Click here for help
Compound class Synthetic organic
Prodrug rodatristat ethyl
IUPAC Name Click here for help
(3S)-8-[2-amino-6-[(1R)-1-(4-chloro-2-phenylphenyl)-2,2,2-trifluoroethoxy]pyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-3-carboxylic acid
International Nonproprietary Names Click here for help
INN number INN
10812 rodatristat
Synonyms Click here for help
compound 15a [PMID: 28041831] | KAR-5417 | KAR5417
Database Links Click here for help
CAS Registry No. 1673568-73-4 (source: WHO INN record)
ChEMBL Ligand CHEMBL4104957
GtoPdb PubChem SID 404859094
PubChem CID 117947705
RCSB PDB Ligand 6Z4
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UniChem Compound Search for chemical match using the InChIKey ZNSPHKJFQDEABI-NZQKXSOJSA-N
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