1182728-22-8

Basic information

• Product Name: 4-(3-benzylsulfanyl-2-chlorophenyl)morpholin-3-one
• Synonyms: 4-(3-benzylsulfanyl-2-chlorophenyl)morpholin-3-one
• CAS NO: 1182728-22-8
• Molecular Weight: 333.839
• Mol File: 1182728-22-8.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: 4-(3-benzylsulfanyl-2-chlorophenyl)morpholin-3-one(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(3-benzylsulfanyl-2-chlorophenyl)morpholin-3-one(1182728-22-8)
• EPA Substance Registry System: 4-(3-benzylsulfanyl-2-chlorophenyl)morpholin-3-one(1182728-22-8)

Safety Data

• Hazardous Substances Data: 1182728-22-8(Hazardous Substances Data)

Upstream product

• 100-53-8 phenylmethanethiol 
• 109-11-5 morpholine-3-one 
• 1182728-20-6 1-benzylsulfanyl-3-bromo-2-chlorobenzene 
• 883499-24-9 1-bromo-2-chloro-3-fluoro benzene 

Downstream Products

• 1182728-24-0 2-chloro-3-(3-oxomorpholin-4-yl)benzenesulfonyl chloride 

Relevant articles and documents

5-chlorothiophene-2-carboxylic acid [(S)-2-[2-Methyl-3-(2-oxopyrrolidin-1- yl)benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amide (SAR107375), a selective and potent orally active dual thrombin and factor Xa inhibitor

Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC 50's of 3.5 and 0.39 μM, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene P1 fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with Ki's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 μM) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a.

CHLOROTHIOPHENE-AMIDES AS INHIBITORS OF COAGULATION FACTORS XA AND THROMBIN

The present invention relates to compounds of the formula I wherein R1; R2; R3; R4; R5, R13, R16, X and M have the meanings indicated in the claims. The compounds of formula I are valuable pharmacologically active compounds. They exhibit a strong anti-thrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and thrombin and can in general be applied in conditions in which an undesired activity of factor Xa and/or thrombin are present or for the cure or prevention of which an inhibition of factor Xa and thrombin are intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.