218301-68-9

Upstream product

• 148-24-3 8-quinolinol 
• 29632-74-4 2-fluro-4-iodoaniline 
• 54534-78-0 (1H-Imidazol-2-ylmethyl)-dimethylamine 
• 218301-69-0 2-fluoro-4-[(2'-dimethylaminomethyl)imidazol-1'-yl]nitrobenzene 
• 367-24-8 4-bromo-2-fluoroaniline 

Downstream Products

• 863015-64-9 5-Chloro-thiophene-2-carboxylic acid {2-[4-(2-dimethylaminomethyl-imidazol-1-yl)-2-fluoro-phenylcarbamoyl]-ethyl}-amide 
• 218299-40-2 1-(3'-aminobenzisoxazol-5'-yl)-3-trifluoromethyl-5-[[4-[(2'-dimethylaminomethyl)imidazol-1'-yl]-2-fluorophenyl]aminocarbonyl]pyrazole TFA salt 
• 553652-21-4 C₂₁H₂₈FN₅O₃ 
• 405940-74-1 1-(3'-cyano-4'-fluorophenyl)-3-trifluoromethyl-N-[2-fluoro-4-[(2'-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide 

Relevant academic research and scientific papers

Structure and property based design of factor Xa inhibitors: Biaryl pyrrolidin-2-ones incorporating basic heterocyclic motifs

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating basic biaryl P4 groups, producing highly potent inhibitors with significant anticoagulant activities and encouraging oral pharmacokinetic profiles.

Heteroarylacetamide inhibitors of factor Xa

The invention is concerned with novel heteroarylacetamides of formula (I) [in-line-formulae]Rd—C(O)—N(Re)—Rc—CH2—C(O)—N(Ra)(Rb) ??(I) [/in-line-formulae] wherein Ra to Re /

TETRAHYDROISOQUINOLINES AS FACTOR XA INHIBITORS

The present invention is directed to compounds represented by Formula I and pharmaceutically acceptable salts, solvates, hydrates, and prodrugs thereof which are inhibitors of Factor Xa. The present invention is also directed to and intermediates used in making such compounds, pharmaceutical compositions containing such compounds, methods to prevent or treat a number of conditions characterized by undesired thrombosis and methods of inhibiting the coagulation of a blood sample.

UREAS AS FACTOR XA INHIBITORS

The present invention is directed to compounds represented by Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, and prodrugs thereof which are inhibitors of Factor Xa. The present invention is also directed to and intermediates used in making such compounds, pharmaceutical compositions containing such compounds, methods to prevent or treat a number of conditions characterized by undesired thrombosis and methods of inhibiting the coagulation of a blood sample.

Discovery of 1-(3′-aminobenzisoxazol-5′-yl)-3-trifluoromethyl- N-[2-fluoro-4-[(2′-dimethylaminomethyl)imidazol-1-yl]phenyl] -1H-pyrazole-5-carboxyamide hydrochloride (razaxaban), a highly potent, selective, and orally bioavailable factor Xa inhibitor

Modification of a series of pyrazole factor Xa inhibitors to incorporate an aminobenzisoxazole as the P1 ligand resulted in compounds with improved selectivity for factor Xa relative to trypsin and plasma kallikrein. Further optimization of the P4 moiety led to compounds with enhanced permeability and reduced protein binding. The SAR and pharmacokinetic profile of this series of compounds is described herein. These efforts culminated in 1-(3′-aminobenzisoxazol-5′-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2′-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide (11d), a potent, selective, and orally bioavailable inhibitor of factor Xa. On the basis of its excellent in vitro potency and selectivity profile, high free fraction in human plasma, good oral bioavailability, and in vivo efficacy in antithrombotic models, the HCl salt of this compound was selected for clinical development as razaxaban (DPC 906, BMS-561389).

Beta-aminoacid-derivatives as factor Xa inhibitors

The present invention relates to compounds of the formula I, in which R0 ; R1 ; R2 ; R3 ; R4; R5, R6, Q; V, G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is 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.

NOVEL GUANIDINE MIMICS AS FACTOR Xa INHIBITORS

The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula (I) or pharmaceutically acceptable salt forms thereof, wherein rings D-E represent guanidine mimics, which are useful as inhibitors of factor Xa.

1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 2: A survey of P4 motifs

A variety of P4 motifs have been examined to increase the binding affinity and in vitro anticoagulant potency of our biphenyl 1-(2-naphthyl)-1H-pyrazole-5- carboxylamide-based fXa inhibitors. Highly potent 2-naphthyl-P1 fXa inhibitors (Ki≤2 nM) with improved in vitro anticoagulant activity (2×TG≤1 μM) and respectable pharmacokinetic properties have been discovered.

Novel N-[4- (1H-imidazol-1-yl) -2-fluorophenyl ] -3- (trifluoromethyl) -1H-pyrazole-5-carboxamides as factor Xa inhibitors

The present application describes N-[4-(1H-imidazol-1-yl)-2-fluorophenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamides and derivatives thereof of, which are useful as inhibitors of factor Xa.

Efficient ligand-mediated ullmann coupling of anilnies and azoles

The present invention provides of method of preparing phenyl-substituted azoles. This method uses an efficient ligand-accelerated Ullmann coupling reaction of anilines with azoles. The coupling products are useful for preparing factor Xa inhibitors.