Patent NZ-514874-A (NZ)
Title: Substituted polycyclic aryl and heteroaryl pyrymidinones useful as anticoagulants
Inventor: SOUTH MICHAEL S
IPC: A61P9/10
Filed: 2000-05-17
Abstract: Substituted polycyclic aryl and heteroaryl pyrimidinones of formula (I) are described wherein: B is the compound of formula (II) wherein R32, R33, R34, R35, and R36 are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano or Qb; A is selected from a single covalent bond and (CH(R15))pa-(W7)rr where rr is 0-1; pa is 0-3; W7 is selected from (R7)NC(O) and N(R7); where R7 is hydrido, hydroxy and alkyl; and R15 is hydrido, halo, alkyl and haloalkyl; M is selected from N and R1-C; where R1 is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo; R2 is Z0-Q; where Z0 is a covalent single bond, O, S, NH or CH2; and Q is selected from aryl and heteroaryl where (a) a ring carbon in a first alpha position relative to the ring carbon at the point of attachment is optionally substituted by R9 (b) a ring carbon in a second alpha position relative to the ring carbon at the point of attachment is optionally substituted by R13 (c) a ring carbon in a first beta position relative to the ring carbon at the point of attachment and in an alpha position relative to the ring atom optionally substituted by R9, is optionally substituted by R10 (d) a ring carbon in a second beta position relative to the ring carbon at the point of attachment and in an alpha position relative to the ring atom optionally substituted by R13, is optionally substituted by R12 and (e) a ring carbon if present in the gamma position relative to the ring carbon at the point of attachment and in an alpha relative to each of the ring atoms optionally substituted by R10 and R12, respectively, is optionally substituted by R11; where R9, R11 and R13 hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano; R10 and R12 are selected from hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl and cyano; and Y0 is formula (IV): where D5, D6, J5 and J6 are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D5, D6, J5 and J6 is a covalent bond, no more than one is O, no more than one is S, one must be a covalent bond when two are O and S, and no more than four are N; R16, R17, R18, and R19 are selected from hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; Qb is selected from NR20R21, hydrido and C(NR25)NR23R24, with the proviso that no more than one of R20 and R21 is hydroxy and that no more than one of R23 and R24 is hydroxy; where R20, R21, R23, R24 and R25 are selected from hydrido, alkyl and hydroxy; and Qs is selected form single covalent bond, CH2 and CH2CH2. The compounds can be used in medicaments for inhibiting thrombotic conditions, formation of blood platelet aggregates and thrombus formation, and for treating or preventing venous thromboembolisms, pulmonary embolisms, deep vein thrombosis, cardiogenic thromboembolism, thromboembolic strokes, thrombus associated with cancer and cancer chemotherapy, unstable angina.