Bitopertin

Bitopertin

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Systematic (IUPAC) name
{4-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}{5-(methylsulfonyl)-2-[(1S)-2,2,2-trifluoro-1-methylethoxy]phenyl}methanone
Identifiers
CAS Number	845614-11-1
ATC code	none
IUPHAR/BPS	7546
ChemSpider	25034798
UNII	Q8L6AN59YY
ChEMBL	CHEMBL1169880
Chemical data
Formula	C21H20F7N3O4S
Molecular mass	543.455022 g/mol
SMILES CC(C(F)(F)F)Oc1ccc(cc1C(=O)N2CCN(CC2)c3c(cc(cn3)C(F)(F)F)F)S(=O)(=O)C
InChI InChI=1S/C21H20F7N3O4S/c1-12(20(23,24)25)35-17-4-3-14(36(2,33)34)10-15(17)19(32)31-7-5-30(6-8-31)18-16(22)9-13(11-29-18)21(26,27)28/h3-4,9-12H,5-8H2,1-2H3/t12-/m0/s1 Key:YUUGYIUSCYNSQR-LBPRGKRZSA-N

Bitopertin (RG1678; RO-4917838) is a glycine reuptake inhibitor which was under development by Roche as an adjunct to antipsychotics for the treatment of persistent negative symptoms or suboptimally-controlled positive symptoms associated with schizophrenia. Research into this indication has been largely halted as a result of disappointing trial results, but Roche continues to develop bitopertin for the treatment of obsessive-compulsive disorder (OCD).

Bitopertin is a glycine transporter 1 (GlyT1) inhibitor that increases levels of the neurotransmitter glycine by inhibiting its reuptake from the synaptic cleft. Glycine acts as a required co-agonist along with glutamate at N-methyl-D-aspartate (NMDA) receptors. Dysfunction of NMDA receptors may play a key role in the pathogenesis of schizophrenia and modulation of glutamatergic signalling via increased concentrations of glycine in the synaptic cleft may help potentiate NMDA receptor function and improve the symptoms of schizophrenia.

In a phase II proof-of-concept study patients on bitopertin experienced a significant improvement in the change of the Negative Symptom Factor Score from baseline within 8 weeks (from −4.86 in the placebo group to −6.65 in the treatment group, p<0.05, per-protocol population). In addition, 83% of patients on bitopertin described an improvement of negative symptoms on the CGI-I1 vs 66% on placebo (p<0.05, per-protocol population).

In January 2014, Roche reported that bitopertin failed to meet its endpoints in two phase III trials assessing its efficacy in reducing negative symptoms of schizophrenia. Subsequently, in April 2014, Roche announced that it was discontinuing all of its phase III trials of bitopertin for schizophrenia except for one.

Though Roche has largely ceased its studies of bitopertin for schizophrenia, it is also investigating the drug in the treatment of obsessive-compulsive disorder (OCD), and is continuing its development for this indication. As of August 2014, bitopertin is in phase II clinical trials for OCD.

See also

• Org 25935