845616-83-3

Upstream product

• 247569-56-8 2-fluoro-5-(methylsulfonyl)benzoic acid 
• 374-01-6 (S)-1,1,1-trifluoro-2-propanol 
• 37098-75-2 2-fluoro-5-chlorosulfonylbenzoic acid 
• 445-29-4 o-fluoro-benzoic acid 
• 865663-98-5 2-fluoro-5-methanesulfonylbenzoic acid methyl ester 
• 374-01-6 1,1,1-trifluoroisopropanol 
• 845617-20-1 5-Methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzoic acid methyl ester 

Downstream Products

• 1421936-37-9 C₂₀H₂₁F₃N₂O₅S 
• 1421936-36-8 C₂₀H₂₁F₃N₂O₅S 
• 1421937-86-1 C₂₁H₂₀F₆N₂O₅S 
• 1421937-87-2 C₂₁H₂₀F₆N₂O₅S 
• 1421937-45-2 C₂₂H₂₄F₃N₃O₆S 
• 1421937-46-3 C₂₂H₂₄F₃N₃O₆S 
• 845614-11-1 Bitopertin 

Relevant academic research and scientific papers

Bitopertin synthetic method and intermediate

The present invention discloses a new synthesis method and intermediates of Bitopertin. According to the Bitopertin synthesis method, 5-methylsulfonyl-2-[(1S)-2,2,2-trifluoro-1-methylethoxy]benzoic acid is adopted as a raw material, and continuous multi-step operations such as chlorination, acylation, deprotection, condensation and re-crystallization are subjected to performed to obtain the Bitopertin, wherein the intermediates in each step do not require further purification, and the total yield can achieve more than or equal to 80%.

Design and Synthesis of Novel and Selective Glycine Transporter-1 (GlyT1) Inhibitors with Memory Enhancing Properties

We report here the identification and optimization of a novel series of potent GlyT1 inhibitors. A ligand design campaign that utilized known GlyT1 inhibitors as starting points led to the identification of a novel series of pyrrolo[3,4-c]pyrazoles amides

Development of a Scalable, Chromatography-Free Synthesis of t-Bu-SMS-Phos and Application to the Synthesis of an Important Chiral CF3-Alcohol Derivative with High Enantioselectivity Using Rh-Catalyzed Asymmetric Hydrogenation

A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach in five steps from the chiral auxiliary in 36% overall yield. Separtion and recovery of the auxiliary were achieved with good yield (97%) to enable recycling of the chiral auxiliary. An air-stable crystalline form of the final ligand was identified to enable isolation of the final ligand by crystallization to avoid chromatography. This synthetic route was applied to prepare up to 4 kg of the final ligand. The utility of this material was demonstrated in the asymmetric hydrogenation of trifluoromethyl vinyl acetate at 0.1 mol % Rh loading to access a surrogate for the pharmaceutically relavent chiral trifluoroisopropanol fragment in excellent yield and enantiomeric excess (98.6%).

Discovery of 4-benzoylpiperidine and 3-(piperidin-4-yl)benzo[d]isoxazole derivatives as potential and selective GlyT1 inhibitors

Regulation of glycine transporter 1 (GlyT1) activity is a currently investigated strategy in drug discovery for schizophrenia. This study developed a series of new 4-benzoylpiperidine derivatives as GlyT1 inhibitors by bioisosteric replacement and mimicking of the pyridine ring of RG1678. Among the 4-benzoylpiperidine derivatives, 23q showed an IC50 of 30 nM. Preliminary optimization of the blood-brain barrier penetration led to the discovery of 3-(piperidin-4-yl)benzo[d]isoxazole derivatives. Both series showed good selectivity over GlyT2, D1, D2, D3, 5-HT1A and 5-HT2A receptors. Moreover, behavioral testing showed 23q (40 mg kg-1, intragastric) can inhibit the hyperlocomotion induced by acute treatment of phencyclidine, and improve the impaired negative and cognitive symptoms in chronic phencyclidine-induced C57BL/6J mice. An interesting finding showed that 3-(piperidin-4-yl)benzo[d]isoxazole was a privileged scaffold of atypical antipsychotic agents but exhibited high selectivity and potency as a GlyT1 inhibitor.

Selective GlyT1 inhibitors: Discovery of [4-(3-fluoro-5- trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2, 2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia

The GlyT1 transporter has emerged as a key novel target for the treatment of schizophrenia. Herein, we report on the optimization of the 2-alkoxy-5-methylsulfonebenzoylpiperazine class of GlyT1 inhibitors to improve hERG channel selectivity and brain penetration. This effort culminated in the discovery of compound 10a (RG1678), the first potent and selective GlyT1 inhibitor to have a beneficial effect in schizophrenic patients in a phase II clinical trial.

Preparation of dihydropyrrol derivatives as intermediates

The invention is concerned with a new scalable process for the preparation of compounds of formula I comprising a new process for the preparation of the key intermediate, a dihydropyrrole derivative formula II or a salt thereof.

SYNTHESIS OF GLYT-1 INHIBITORS

The present invention relates to a process for preparation of a compound of formula I wherein Het, R1, R2, R3, and n are as defined herein and pharmaceutically acceptable acid addition salts thereof, which comprises reacting a compound of formula 21 with a compound of formula 8 to obtain a compound of formula 11 and coupling the compound of formula 11 in the presence of a coupling reagent or the corresponding acid halogenide with a compound of formula 15 to obtain a compound of formula I.

[4-(HETEROARYL) PIPERAZIN-1-YL]-(2,5-SUBSTITUTED -PHENYL)METHANONE DERIVATIVES AS GLYCINE TRANSPORTER 1 (GLYT-1) INHIBITORS FOR THE TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS

The present invention relates to compounds of the general formula (I) wherein R1 is-OR1’,-SR1’ or is a heterocycloalkyl group; R1’ is lower alkyl, lower alkyl substituted by halogen or is -(CH2)n

Substituted phenyl methanone derivatives

The present invention relates to compounds of formula I wherein R1, R2, R3, n, and m, are as defined in the specification and to pharmaceutically acceptable acid addition salts thereof. These compounds are good inhibitors

Substituted phenyl methanones

The present invention relates to compounds of general formula IA or IB wherein X1 and X2 are each independently N or C—R″ and R1, R2,R3, R4, R5, and R6 are as defined