553653-11-5Relevant academic research and scientific papers
Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with monoaryl P4 motifs
Kleanthous, Savvas,Borthwick, Alan D.,Brown, David,Burns-Kurtis, Cynthia L.,Campbell, Matthew,Chaudry, Laiq,Chan, Chuen,Clarte, Marie-Olive,Convery, Maire A.,Harling, John D.,Hortense, Eric,Irving, Wendy R.,Irvine, Stephanie,Pateman, Anthony J.,Patikis, Angela N.,Pinto, Ivan L.,Pollard, Derek R.,Roethka, Theresa J.,Senger, Stefan,Shah, Gita P.,Stelman, Gary J.,Toomey, John R.,Watson, Nigel S.,West, Robert I.,Whittaker, Caroline,Zhou, Ping,Young, Robert J.
scheme or table, p. 618 - 622 (2010/06/12)
Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa inhibitors, incorporating neutral and basic monoaryl P4 groups, ultimately producing potent inhibitors with effective levels of anticoagulant activity and extended oral pharmacokinetic profiles. However, time dependant inhibition of Cytochrome P450 3A4 was a particular issue with this series.
1-PHENYL-2-OXO-3-SULFONYLAMINO-PYRROLIDINE DERIVATIVES AND RELATED COMPOUNDS AS FACTOR XA INHIBITORS FOR THE TREATMENT OF ACUTE VASCULAR DISEASES
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Page/Page column 29, (2010/02/09)
The invention relates to compounds of formula (I) wherein: R1 represents a group selected from: formula (II) each ring of which optionally contains a further heteroatom N, Z represents an optional substituent halogen, alk represents alkylene or alkenylene, T represents S, O or NH; R2 represents -C1-6alkyl, -C1-3alkylCN, -C0-3alkylRc, -C1-3alkylRf, -C2-3alkylNRaRb, -C2-3alkylOC1-6alkyl, -C2-3alkylOC1-3alkylCONRaRb, with the proviso that R2 does not represent C2-3alkylmorpholino; X represents phenyl or a 5- or 6- membered aromatic heterocyclic group containing at least one heteroatom selected from O, N or S, each of which is optionally substituted by 0-2 groups selected from: halogen, -C1-4alkyl, -C2-4alkenyl, -CN, -CF3, -NRaRb, -C0-4alkylORe, -C(O)Rd and -C(O)NRaRb; Y represents a substituent selected from hydrogen, halogen, -C1-4alkyl, -C2-4alkenyl, -NRaRb, -NO2, -C(O)NRaRb, -N(C1-4alkyl)(CHO), -NHCOC1-4alkyl, -NHSO2Rd, -C0-4alkylORe, -C(O)Rd, -S(O)nRd, or -S(O)2NRaRb; The other substituents are as defined in claim 1.
