- Phosphinanes and Azaphosphinanes as Potent and Selective Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa)
-
Selective and potent inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa) have the potential to increase endogenous and therapeutic fibrinolysis and to behave like profibrinolytic agents without the risk of major hemorrhage, since they do not interfere either with platelet activation or with coagulation during blood hemostasis. Therefore, TAFIa inhibitors could be used in at-risk patients for the treatment, prevention, and secondary prevention of stroke, venous thrombosis, and pulmonary embolisms. In this paper, we describe the design, the structure-activity relationship (SAR), and the synthesis of novel, potent, and selective phosphinanes and azaphosphinanes as TAFIa inhibitors. Several highly active azaphosphinanes display attractive properties suitable for further in vivo efficacy studies in thrombosis models.
- Schaffner, Arnaud-Pierre,Sansilvestri-Morel, Patricia,Despaux, Nicole,Ruano, Elisabeth,Persigand, Thierry,Rupin, Alain,Mennecier, Philippe,Vallez, Marie-Odile,Raimbaud, Eric,Desos, Patrice,Gloanec, Philippe
-
supporting information
p. 3897 - 3910
(2021/05/04)
-
- COMPOUNDS OF PHOSPHINANES AND AZAPHOSPHINANES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
-
Compounds of formula (I) wherein: Ak1 represents an alkyl chain, X represents —(CH2)m—, —CH(R)—, —N(R)—, —CH2—N(R)—, —N(R)—CH2— or —CH2—N(R)—CH2—, m and R are as defined in the description, R1 and R2 each represent H when X represents —(CH2)m—, —CH(R)—, —N(R)—, —CH2—N(R)— or —N(R)—CH2—, or together form a bond when X represents —CH2—N(R)—CH2—, R3 represents NH2, Cy-NH2, Cy-Ak3-NH2 or piperidin-4-yl, Cy and Ak3 are as defined in the description, R4 and R5, which may be identical or different, each represent H or F, their optical isomers, and addition salts thereof with a pharmaceutically acceptable acid. Medicinal products containing the same which are useful in treating conditions requiring a TAFIa inhibitor.
- -
-
Paragraph 0251; 0252; 0253; 0254; 0255; 0256
(2018/02/27)
-
- Insertion of Arynes into P-O Bonds: One-Step Simultaneous Construction of C-P and C-O Bonds
-
The insertion of arynes into P-O bonds for the preparation of o-hydroxy-substituted arylphosphine oxides, -phosphinates, and -phosphonates is described. This novel reaction leads to the simultaneous formation of C-P and C-O bonds in one step with good yie
- Qi, Na,Zhang, Ning,Allu, Srinivasa Rao,Gao, Jiangsheng,Guo, Jian,He, Yun
-
supporting information
p. 6204 - 6207
(2016/12/09)
-
- Diastereoselective ring-closing metathesis: Synthesis of P-stereogenic phosphinates from prochiral phosphinic acid derivatives
-
The preparation of phosphorus-containing trienes featuring two diastereotopic vinyl moieties followed by a diastereoselective ring-closing metathesis is described. This methodology allowed for the synthesis of novel highly functionalized P-stereogenic het
- Dunne, Katherine S.,Bisaro, Fabrice,Odell, Barbara,Paris, Jean-Marc,Gouverneur, Veronique
-
p. 10803 - 10809
(2007/10/03)
-