NEW ANTIFIBRINOLYTIC COMPOUNDS

摘要

It relates to spirocyclic compounds of formula (I), or pharmaceutically or veterinary acceptable salts thereof, or any stereoisomers either of the compounds of formula (I) or of their pharmaceutically or veterinary acceptable salts, wherein A and B form a spirocyclic ring system wherein the spiro atom connecting A and B is a carbon atom and wherein A is a known 3- to 8-membered carbocyclic or heterocyclic monocyclic ring or a known 6- to 18-membered carbocyclic or heterocyclic polycyclic ring system; B is a known 4- to 7-membered carbocyclic or heterocyclic monocyclic ring; C is phenyl or a known 5- to 6-membered heteroaromatic ring; and R1-R7 are as defined herein. It also relates to a process for their preparation, as well as to the intermediates used in this process; to pharmaceutical or veterinary compositions containing them, and to their use in medicine, in particular as antifibrinolytic and antihemorragic agents.;

主权项

1. A compound of formula (I), or a pharmaceutically or veterinary acceptable salt thereof, or any stereoisomer either of the compound of formula (I) or of its pharmaceutically or veterinary acceptable saltwherein
A and B form a spirocyclic ring system wherein the spiro atom connecting A and B is a carbon atom and wherein A is a known 3- to 8-membered carbocyclic or heterocyclic monocyclic ring, saturated or partially unsaturated; or alternatively A is a known 6- to 18-membered carbocyclic or heterocyclic polycyclic ring system, saturated, partially unsaturated, or partially aromatic; and B is a known 4- to 7-membered carbocyclic or heterocyclic monocyclic ring, saturated or partially unsaturated; C is phenyl or a known 5- to 6-membered heteroaromatic ring; R1-R3 are independently selected from H, halogen, —NO2, —CN, Ra, —ORa′, —OC(Y)Ra′, —OC(Y)ORa′, —OC(Y)NRbRa′, —OSO2ORa′, —NRbRa′, —NRbC(Y)Ra′, —NRbC(Y)ORa′, —NRbC(Y)NRbRa′, —NRbS(O)2Ra′, —NRbSO2NRbRa′, —SRa′, —S(O)Ra′, —S(O)ORa′, —SO2Ra′, —SO2(ORa′), —SO2NRbRa′, —SC(Y)NRbRa′, —C(Y)Ra′, —C(Y)ORa′, —C(Y)NRbRa′, —C(Y)NRbORa′, and —C(O)NRbSO2Ra′; R4-R7 are independently selected from halogen, —NO2, —CN, Rc, —ORc, —NRdRc, —NRdC(Y)Rc, —NRdC(Y)ORc, —NRdC(Y)NRdRc, —NRdS(O)2Rc, —NRdSO2NRdRc, —SRc, —S(O)Rc, —S(O)ORc, —SO2Rc, —SO2R(ORc), —SO2NRdRc, —SC(Y)NRdRc, —C(Y)Rc, —C(Y)ORc, —C(Y)NRdRc, —C(Y)NRdORc, and —C(O)NRdSO2Rc; Ra is a saturated or unsaturated (C1-C12)alkyl optionally substituted with one or more substituents Re and/or one Cy1; or alternatively Ra is Cy2; wherein Cy1 and Cy2 are independently optionally substituted with: one Cy3 and/or one or more substituents Re, and/or one or more saturated or unsaturated (C1-C6)alkyl groups optionally substituted with one or more substituents Re and/or one Cy3; and wherein any Cy3 is optionally substituted with one or more substituents independently selected from Re and saturated or unsaturated (C1-C6)alkyl optionally substituted with one or more substituents Re; each Ra′ and Rb are independently H or Ra; Rc and each Rd are independently selected from H, Cy4, and saturated or unsaturated (C1-C6)alkyl optionally substituted with one or more substituents Rh and/or one Cy5; wherein Cy4 is optionally substituted with one or more substituents independently selected from Rh and saturated or unsaturated (C1-C6)alkyl optionally substituted with one or more substituents Rh; and wherein Cy5 is optionally substituted with one or more substituents independently selected from Rh and saturated or unsaturated (C1-C6)alkyl optionally substituted with one or more substituents Rh; each Re is independently selected from halogen, —NO2, —CN, —ORf, —OC(Y)Rf, —OC(Y)ORf, —OC(Y)NRgRf, —NRgRf, —NRgC(Y)Rf, —NRgC(Y)ORf, —NRgC(Y)NRgRf, —NRgS(O)2Rf, —NRgSO2NRgRf, —SRf, —S(O)Rf, —S(O)ORf, —SO2Rf, —SO2(ORf), —SO2NRgRf, —SC(Y)NRgRf, —C(Y)Rf, —C(Y)ORf, —C(Y)NRgRf, —C(Y)NRgORf, and —C(O)NRgSO2Rf; Rf and each Rg are independently selected from H, Cy6, and saturated or unsaturated (C1-C6)alkyl optionally substituted with one or more substituents Rh and/or one Cy7; wherein Cy6 is optionally substituted with: one Cy7, and/or one or more substituents Rh, and/or one or more saturated or unsaturated (C1-C6)alkyl groups optionally substituted with one or more substituents Rh and/or one Cy7; and wherein any Cy7 is optionally substituted with one or more substituents independently selected from Rh and (C1-C4)alkyl optionally substituted with one or more substituents Rh; each Rh is independently selected from halogen, —NO2, —CN, —ORi, —OC(O)Ri, —OC(O)ORi, —OC(O)NRiRi, —NRiRi, —NRiC(O)Ri, —NRiC(O)ORi, —NRiC(O)NRiRi, —NRiS(O)2Ri, —NRiSO2NRiRi, —SRi, —S(O)Ri, —SO2Ri, —SO2(ORi), —SO2NRiRi, —C(O)Ri, —C(O)ORi, —C(O)NRiRi, and —C(O)NRiORi; each Ri is independently H or —(C1-C4)alkyl optionally substituted with one or more halogen atoms; Y is O, S, or NRg; Cy1, Cy2, Cy4 and Cy6 are independently a C or N-attached known ring system selected from 3- to 8-membered carbocyclic or heterocyclic monocyclic ring, saturated or partially unsaturated; phenyl; 5- or 6-membered heteroaromatic ring; and 6- to 18-membered carbocyclic or heterocyclic polycyclic ring system, saturated, partially unsaturated, aromatic or partially aromatic; Cy3, Cy5 and Cy7 are independently a C or N-attached known ring system selected from 3- to 8-membered carbocyclic or heterocyclic monocyclic ring, saturated or partially unsaturated; phenyl; and 5- or 6-membered heteroaromatic ring; wherein in the carbocyclic rings all ring members are carbon atoms; and in the heterocyclic and heteroaromatic rings one or more ring members are selected from N, O, and S; and wherein in all saturated or partially unsaturated rings one or two members of the rings are optionally C(O) and/or C(NH) and/or C[N(C1-C4)alkyl].