3-ureidoisoquinolin-8-yl derivatives

摘要

The invention relates to 3-ureidoisoquinolin-8-yl derivatives of formula I;whereinR1 is alkyl, haloalkyl or cyclopropyl;R2 is H, halogen, pyridazin-4-yl, pyrimidin-5-yl or an optionally substituted pyridin-3-yl, pyridin-4-yl or phenyl group;R3 is alkyl, alkynyl, aminoalkyl, carbamoylalkyl, methylcarbamoylalkyl, alkoxy, haloalkoxy, alkynyloxy, (4-hydroxybut-2-yn-1-yl)oxy, (4-aminobut-2-yn-1-yl)oxy, dimethylaminoalkoxy, carbamoylalkoxy, alkylamino, cycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, hydroxyalkyl, hydroxyalkoxy, alkoxyalkyl, alkoxyalkoxy, carboxyalkyl, carboxyalkoxy, alkoxycarbonylalkoxy, aryl, heteroaryl, benzyl, benzyloxy, 2-cyanoethoxy, 2,3-dihydroxypropoxy, 3,4-dihydroxybutoxy, —CH2Ra, —CH2CH2Rb, —(CH2)n—C(O)O—Rd, —(CH2)n—N(Rc)C(O)O—Rd, —O—(CH2)n—N(Rc)C(O)O—Rd, —(CH2)n—Re or —O—(CH2)n—Re; Ra is cyano, acetylamino or N,N-dimethylamino; Rb is cyano or carbamoyl; Rc is H or methyl; Rd is alkyl; Re is pyrrolidin-1-yl, piperidin-1-yl, piperidin-3-yl, morpholin-1-yl, 2-oxopyrrolidin-1-yl, 5-oxopyrrolidin-2-yl, 2,5-dioxopyrrolidin-1-yl, 2-oxoimidazolidin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 4-(aminomethyl)cyclohexyl or heteroaryl;R4 is H or methyl;and to the salts of such compounds.These compounds are useful for the prevention or the treatment of bacterial infections.

主权项

1. A compound of formula I wherein R1 is (C1-C3)alkyl, (C2-C3)haloalkyl or cyclopropyl; R2 is H, halogen, pyridazin-4-yl, pyrimidin-5-yl or a group having the formula (A1), (A2) or (A3) shown hereafter wherein Rx is H and each of Ry and Rz is independently H or methyl, or each of Rx and Rz is H and Ry is halogen, cyano, (C2-C4)alkyl, (C1-C4)alkoxy, amino, hydroxy, hydroxy-(C1-C3)alkyl, trifluoromethyl, carbamoyl, carbamoyl-(C1-C2)alkyl, (methylcarbamoyl)-(C1-C2)alkyl, (dimethylcarbamoyl)-(C1-C2)alkyl, tert-butoxycarbonylmethyl, cyclopropyl, pyrrolidin-1-yl, piperidin-1-yl, morpholin-1-yl or 1-morpholinomethyl, or Rx is H and each of Ry and Rz is independently halogen, or Rx is methyl, Ry is methyl or halogen and Rz is H, or Rx is methyl or halogen, Ry is H and Rz is methyl or halogen, or Rx is methyl or halogen and each of Ry and Rz is H; Rx2 is H, amino or hydroxymethyl; Rx3 is hydroxy, carboxy, carbamoyl, hydroxymethyl or aminomethyl, Ry3 is H and Rz3 is H or each of Rx3 and Rz3 is H and Ry3 is hydroxy, acetamidomethyl, (dimethylamino)methyl, carboxymethyl, carbamoyl or aminomethyl, or each of Rx3 and Ry3 is H and Rz3 is hydroxy; R3 is (C1-C4)alkyl, (C2-C4)alkynyl, amino-(C1-C3)alkyl, carbamoyl-(C1-C3)alkyl, (methylcarbamoyl)-(C1-C3)alkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, (C3-C4)alkynyloxy, (4-hydroxybut-2-yn-1-yl)oxy, (4-aminobut-2-yn-1-yl)oxy, dimethylamino-(C2-C3)alkoxy, carbamoyl-(C1-C3)alkoxy, (C1-C3)alkylamino, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C4)alkyl, (C3-C6)cycloalkyl-(C1-C4)alkoxy, hydroxy-(C1-C3)alkyl, hydroxy-(C2-C3)alkoxy, (C1-C3)alkoxy-(C1-C3)alkyl, (C1-C3)alkoxy-(C1-C3)alkoxy, carboxy-(C1-C3)alkyl, carboxy-(C1-C3)alkoxy, (C1-C2)alkoxycarbonyl-(C1-C3)alkoxy, aryl, (C5-C6)heteroaryl, benzyl, benzyloxy, 2-cyanoethoxy, 2,3-dihydroxypropoxy, 3,4-dihydroxybutoxy, —CH2Ra, —CH2CH2Rb, —(CH2)n—C(O)O—Rd, —(CH2)n—N(Rc)C(O)O—Rd, —O—(CH2)n—N(Rc)C(O)O—Rd, —(CH2)n—Re or —O—(CH2)n—Re; n is 1, 2 or 3; Ra is cyano, acetylamino, N,N-dimethylamino; and Rb is cyano or carbamoyl; Rc is H or methyl; Rd is (C1-C4)alkyl; Re is pyrrolidin-1-yl, piperidin-1-yl, piperidin-3-yl, morpholin-1-yl, 2-oxopyrrolidin-1-yl, 5-oxopyrrolidin-2-yl, 2,5-dioxopyrrolidin-1-yl, 2-oxoimidazolidin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 4-(aminomethyl)cyclohexyl or (C5-C6)heteroaryl; R4 is H or methyl; or a salt thereof.