US2010075924A1PendingUtilityA1
Dutpase inhibitors
Est. expiryJan 8, 2024(expired)· nominal 20-yr term from priority
Inventors:Ian GilbertCorinne NguyenGian Filippo RudaAlessandro SchhipaniGanasan KasinathanNils-Gunnar JohanssonDolores Gonzales Pacanowska
A61K 31/7072C07D 405/06C07D 239/54A61P 33/06C07F 7/1804A61P 33/00A61K 31/505A61K 31/506Y02A50/30
72
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Claims
Abstract
Deoxyuridine derivatives of the formula where A is O, S or CH 2 ; B is O, S or CHR 3 ; R 1 is H, or various substituents; R 2 is H, F; R 3 is H, F, OH, NH 2 ; or R 2 and R 3 together form a chemical bond; D is —NHCO—, —CONH—, —O—, —C(═O)—, —CH═CH, —C ═ C—, —NR 5 —; R 4 is hydrogen or various substituents; R 5 is H, C 1 -C 4 alkyl, C 1 -C 4 alkanoyl; E is Si or C; R 6 , R 7 and R 8 are independently selected from C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, or a stable monocyclic, bicyclic or tricyclic ring system have utility in the prophylaxis o treatment of parasitic diseases such as malaria
Claims
exact text as granted — not AI-modified1 . Use of a compound of formula I′, in the manufacture of a medicament for the treatment or prophylaxis of plasmodium infections in mammals, including man.
where
A is O, S or CH 2 ;
B is O, S or CHR 3 ;
R 1 is H, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl or a 5 or 6 membered, saturated or unsaturated ring containing 0 to 3 heteroatoms selected from N, O and S, the alkyl, alkenyl, alkynyl or ring being independently optionally substituted with R 4 ;
R 2 is H, F;
R 3 is H, F, OH, NH 2 or a pharmaceutically acceptable ester, amide or ether thereof; or
R 2 and R 3 together form a chemical bond;
D is —NHCO—, —CONH—, —O—, —C(═O)—, —CH═CH, —C ═ C—, —NR 5 —;
R 4 is independently selected from hydrogen, halo, cyano, amino, nitro, carboxy, carbamoyl, hydroxy, oxo, C 1 -C 5 alkyl, C 1 -C 5 haloalkyl, C 1 -C 5 alkyloxy, C 1 -C 5 alkanoyl, C 1 -C 5 alkanoyloxy, C 1 -C 5 alkylthio, —N(C 0 -C 3 -alkyl) 2 , hydroxymethyl, aminomethyl, carboxymethyl;
—SO n N(C 0 -C 3 -alkyl), —SO n C 1 -C 5 -alkyl, where n is 1 or 2;
R 5 is H, C 1 -C 4 alkyl, C 1 -C 4 alkanoyl;
E is Si or C;
R 6 , R 7 and R 8 are independently selected from C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, or a stable monocyclic, bicyclic or tricyclic ring system which is saturated or unsaturated in which each ring has 0 to 3 heteroatoms selected from N, O and S;
R 6 , R 7 and R 8 are independently optionally substituted with R 4 ;
with the proviso that if R 3 is H, OH, F, NH 2 or a bond, then at least one of R 6 , R 7 and/or R 8 comprises an unsaturated ring;
or a pharmaceutically acceptable salts thereof.
2 . Use according to claim 1 , wherein A is —O— and B is —CHR 3 —, or A is —O— and B is —S—.
3 . Use according to claim 1 , wherein R 2 and R 3 form a chemical bond.
4 . Use according to claim 1 , wherein R 3 is OH, NH 2 or F.
5 . Use according to claim 1 , wherein R 1 is H.
6 . Use according to claim 1 , wherein C 0 -C 3 -alkylene-D-C 0 -C 3 -alkylene is oxymethylene, oxyethylene or oxypropylene.
7 . Use according to claim 1 , wherein C 0 -C 3 -alkylene-D-C 0 -C 3 -alkylene is aminomethylene, aminoethylene or aminopropylene.
8 . Use according to claim 1 , wherein at least two of R 6 , R 7 and R 8 have an aromatic nature.
9 . Use according to claim 1 , wherein R 6 is optionally substituted phenyl.
10 . Use according to claim 9 , wherein R 8 is optionally substituted phenyl or pyridyl.
11 . Use according to claim 1 , wherein E is C.
12 . A compound of the formula I
where
A is O, S or CH 2 ;
B is O, S or CHR 3 ;
R 1 is H, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl or a 5 or 6 membered, saturated or unsaturated ring containing 0 to 3 heteroatoms selected from N, O and S, the alkyl, alkenyl, alkynyl or ring being independently optionally substituted with R 4 ;
R 2 is H, F;
R 3 is H, F, OH, NH 2 or a pharmaceutically acceptable ester, amide or ether thereof; or
R 2 and R 3 together form a chemical bond;
D is ONHCO—, —CONH—, —O—, —C(═O)—, —CH═CH, —C ═ C—, —NR 5 —;
R 4 is independently selected from hydrogen, halo, cyano, amino, nitro, carboxy, carbamoyl, hydroxy, oxo, C 1 -C 5 alkyl, C 1 -C 5 haloalkyl, C 1 -C 5 alkyloxy, C 1 -C 5 alkanoyl, C 1 -C 5 alkanoyloxy, C 1 -C 5 alkylthio, —N(C 0 -C 3 -alkyl) 2 , hydroxymethyl, aminomethyl, carboxymethyl; —SO n N(C 0 -C 3 -alkyl), —SO n C 1 -C 5 -alkyl, where n is 1 or 2;
R 5 is H, C 1 -C 4 -alkyl, C 1 -C 4 -alkanoyl;
E is Si or C;
R 6 and R 7 are independently a stable monocyclic, bicyclic or tricyclic ring system which has an aromatic nature and wherein each ring has 0 to 3 heteroatoms selected from N, O and S;
R 8 is C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, or a stable monocyclic, bicyclic or tricyclic ring system which is saturated or unsaturated and in which each ring has 0 to 3 heteroatoms selected from N, O and S;
R 6 , R 7 and R 8 are independently optionally substituted with R 4 ;
with the proviso that if the group C 0 -C 3 alkyl-D-C 0 -C 3 alkyl is —O—CH 2 —, then the group E(R6)(R7)(R8) is not CPh 3 (trityl), methoxylated trityl or tert.butyldiphenylsilyl;
and pharmaceutically acceptable salts thereof.
13 . A compound according to claim 12 , wherein A is —O— and B is —CHR 3 —, or A is —O and B is —S—.
14 . A compound according to claim 12 , wherein R 2 and R 3 form a chemical bond.
15 . A compound according to claim 12 , wherein R 3 is OH, NH 2 or F.
16 . A compound according to claim 12 , wherein R 1 is H.
17 . A compound according to claim 12 , wherein C 0 -C 3 -alkylene-D-C 0 -C 3 -alkylene is oxymethylene, oxyethylene or oxypropylene.
18 . A compound according to claim 12 , wherein C 0 -C 3 -alkylene-D-C 0 -C 3 -alkylene is aminomethylene, aminoethylene or aminopropylene.
19 . A compound according to claim 12 , wherein R 6 is optionally substituted phenyl.
20 . A compound according to claim 19 wherein R 7 is optionally substituted phenyl or pyridyl.
21 . A compound according to claim 12 wherein E is C.
22 . A pharmaceutical composition comprising a compound as defined in claim 12 and a pharmaceutically acceptable carrier or diluent therefor.
23 . Use of a compound as defined in claim 12 in the manufacture of a medicament for the treatment or prophylaxis of parasite infections in mammals, including man.
24 . Use according to claim 23 , wherein the parasite is a trypanosome or Leishmania species.Cited by (0)
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