Patent HR-P20192051-B1 (HR)
Inventor: GUILLEMONT JEROME EMILE GEORGES
IPC: C07D417/12
Filed: 2002-08-09
Abstract: <IMAGE NAME="20192051_01" TYPE="JPG" CENTER=TRUE/><BR/>Ovaj izum bavi se inhibitorima replikacije HIV-a formule (I), njihovim N-oksidima, farmaceutski prihvatljivim adicijskim solima, kvaternarnim aminima i stereokemijski izomernim oblicima, pri čemu prsten koji sadrži -a<SUP>1</SUP>=a<SUP>2</SUP>-a<SUP>3</SUP>=a<SUP>4</SUP>- i -b<SUP>1</SUP>=b<SUP>2</SUP>-b<SUP>3</SUP>=b<SUP>4</SUP>- predstavlja fenil, piridil, pirimidinil, pirazinil, piridazinil; n je 0 do 5; m je 1 do 4; R<SUP>1</SUP> je vodik; aril; formil; C<SUB>1-6</SUB>alkilkarbonil; C<SUB>1-6</SUB>alkil; C<SUB>1-6</SUB>alkiloksikarbonil; supstituirani C<SUB>1-6</SUB>alkil, C<SUB>1-6</SUB>alkilkarbonil; R<SUP>2</SUP> je hidroksi, halo, moguće supstituirani C<SUB>1-6</SUB>alkil, C<SUB>3-7</SUB>cikloalkil, moguće supstituirani C<SUB>2-6</SUB>alkenil, moguće supstituirani C<SUB>2-6</SUB>alkinil, C<SUB>1-6</SUB>alkiloksi, C<SUB>1-6</SUB>alkiloksikarbonil, karboksil, cijano, nitro, amino, mono- ili di(C<SUB>1-6</SUB>alkil)amino, polihalometil, polihalometiloksi, polihalometiltio, -S(=O)<SUB>p</SUB>R<SUP>6</SUP>, -NH-S(=O)<SUB>p</SUB>R<SUP>6</SUP>, -C(=O)R<SUP>6</SUP>, -NHC(=O)H, -C(=O)NHHH<SUB>2</SUB>, -NHC(=O)R<SUP>6</SUP>, -C(=NH)R<SUP>6</SUP> ili 5-člani heterocikl; X<SUB>1</SUB> je -NR<SUP>5</SUP>-, -NH-NH-, -N=N-, -O-, -C(=O)-, C<SUB>1-4</SUB>alkandiil, -CHOH-, -S-, -S(=O)<SUB>p</SUB>-, -X<SUB>2</SUB>-C<SUB>1-4</SUB>alkandlil ili -C<SUB>1-4</SUB>alkandiil-X<SUB>2</SUB>-; R<SUP>3</SUP> je NHR<SUP>13</SUP>; NR<SUP>13</SUP>R<SUP>14</SUP>; -C(=O)-NHR<SUP>13</SUP>; -C(=O)-NR<SUP>13</SUP>R<SUP>14</SUP>; -C(=O)-R<SUP>15</SUP>; -CH=N-NH-C(=O)-R<SUP>16</SUP>; supstituirani C<SUB>1-6</SUB>alkil; moguće supstituirani C<SUB>1-6</SUB>alkiloksiC<SUB>1-6</SUB>alkil, supstituirani C<SUB>2-6</SUB>alkenil, supstituirani C<SUB>2-6</SUB>alkinil, C<SUB>1-6</SUB>alkil supstituiran s hidroksi i još jednim supstituentom, -C(=N-O-R<SUP>8</SUP>)-C<SUB>1-4</SUB>alkil; R<SUP>7</SUP> ili –X<SUB>3</SUB>-R<SUP>7</SUP>; R<SUP>4</SUP> je halo, hidroksi, C<SUB>1-6</SUB>alkil, C<SUB>3-7</SUB>cikloalkil, C<SUB>1-6</SUB>alkiloksi, cijano, nitro, polihaloC<SUB>1-6</SUB>alkil, polihaloC<SUB>1-6</SUB>alkiloksi, aminokarbonil, C<SUB>1-6</SUB>alkiloksikarbonil, C<SUB>1-6</SUB>alkilkarbonil, formil, amino, mono- ili di (C<SUB>1-4</SUB>alkil); njihovom uporabom kao lijeka, postupcima njihova pripravljanja i farmaceutskim pripravcima koji ih uključuju.  <IMAGE NAME="20192051_01" TYPE="JPG" CENTER=TRUE/><BR/>The present invention relates to HIV replication inhibitors of formula (I), their N-oxides, pharmaceutically acceptable addition salts, quaternary amines and stereochemically isomeric forms, wherein the ring containing -a<SUP>1</SUP> = a<SUP>2</SUP>-a<SUP>3</SUP> = a<SUP>4</SUP>- and -b<SUP>1</SUP> = b<SUP>2</SUP> -b<SUP>3</SUP> = b<SUP>4</SUP>- represents phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl; n is 0 to 5; m is 1 to 4; R <SUP>1</SUP> is hydrogen; aryl; formyl; C<SUB>1-6</SUB>alkylcarbonyl; C<SUB>1-6</SUB>alkyl; C<SUB>1-6</SUB>alkyloxycarbonyl; substituted C<SUB>1-6</SUB>alkyl, C<SUB>1-6</SUB>alkylcarbonyl; R<SUP>2</SUP> is hydroxy, halo, optionally substituted C<SUB>1-6</SUB>alkyl, C<SUB>3-7</SUB>cycloalkyl, optionally substituted C<SUB>2-6</SUB>alkenyl, optionally substituted C<SUB>2-6</SUB>alkynyl, C<SUB>1-6</SUB>alkyloxy, C<SUB>1-6</SUB>alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di (C<SUB>1-6</SUB>alkyl) amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, -S(=O)<SUB>p</SUB>R<SUP>6</SUP>, -NH-S(=O)<SUB>p</SUB>R<SUP>6</SUP>, -C(=O)R<SUP>6</SUP>, -NHC(=O)H, -C(=O) NHNH<SUB>2</SUB>, -NHC(=O)R<SUP>6</SUP>, -C(=NH)R<SUP>6</SUP> or a 5-membered heterocycle; X<SUB>1</SUB> is -NR<SUP>5</SUP>-, -NH-NH-, -N=N-, -O-, -C(=O)-, C<SUB>1-4</SUB>alkanediyl, -CHOH-, -S-, -S(=O)<SUB>p</SUB>- , -X<SUB>2</SUB>-C<SUB>1-4</SUB>alkanediyl or –C<SUB>1-4</SUB>alkanediyl-X<SUB>2</SUB>-; R<SUP>3</SUP> is NHR<SUP>13</SUP>; NR<SUP>13</SUP>R<SUP>14</SUP>; -C(=O)-NHR<SUP>13</SUP>; -C(=O) -NR<SUP>13</SUP>R<SUP>14</SUP>; -C(=O) -R<SUP>15</SUP>; -CH=N-NH-C(=O)-R<SUP>16</SUP>; substituted C<SUB>1-6</SUB>alkyl; optionally substituted C<SUB>1-6</SUB> alkyloxyC <SUB>1-6</SUB>alkyl, substituted C<SUB>2-6</SUB> alkenyl, substituted C<SUB>2-6</SUB> alkynyl, C<SUB>1-6</SUB>alkyl substituted with hydroxy and another substituent, -C(=N-O-R<SUP>8</SUP>) -C<SUB>1-4</SUB>alkyl; R<SUP>7</SUP> or -X<SUB>3</SUB>-R<SUP>7</SUP>; R<SUP>4</SUP> is halo, hydroxy, C<SUB>1-6</SUB>alkyl, C<SUB>3-7</SUB>cycloalkyl, C<SUB>1-6</SUB>alkyloxy, cyano, nitro, polyhaloC<SUB>1-6</SUB>alkyl, polyhaloC<SUB>1-6</SUB>alkyloxy, aminocarbonyl, C<SUB>1-6</SUB>alkyloxycarbonyl, C<SUB>1-6</SUB>alkylcarbonyl, formyl, amino, mono- or di (C<SUB>1-4</SUB>alkyl); their use as a medicament, the methods of their preparation and the pharmaceutical compositions which include them.