| 摘要 |
Hypophosphorous acid derivatives having Formula (I) wherein . M is a [C(R3,R4)]n1 - C(E,COOR1, N(H, Z)) group, or an optionally substituted Ar-CH(COOR1, N(H, Z)) group, or an a, ß, or a ß, g-cyclic aminoacid; . R<SUB>1</SUB> is H or R, R being an hydroxy or a carboxy protecting group; . Z is H or an amino protecting group R', benzyl oxycarbonyl, benzyl or benzyl substituted; . E is H or a C1-C3 alkyl, aryl, an hydrophobic group; . R<SUB>2</SUB> is selected in the group comprising: D-CH(R<SUB>6</SUB>)- C-(R<SUB>7</SUB>, R<SUB>8</SUB>), (R<SUB>11</SUB>,R<SUB>12</SUB>)CH- C(R<SUB>9</SUB>, R<SUB>10</SUB>), D - CH(OH), D- [C(R<SUB>13</SUB>, R<SUB>14</SUB>)]<SUB>n3</SUB> -, C[(R<SUB>15</SUB>, R<SUB>16</SUB>, R<SUB>17</SUB>)]<SUB>n4</SUB>, D-CH<SUB>2</SUB>, (R<SUB>18</SUB>)CH = C(R<SUB>19</SUB>), D-(M<SUB>1</SUB>)<SUB>n6</SUB>-CO, Formula (II), PO(OH)<SUB>2</SUB>-CH<SUB>2</SUB> or (PO(OH)<SUB>2</SUB>-CH<SUB>2</SUB>), (COOH-CH<SUB>2</SUB>)-CH<SUB>2</SUB>, with - D = H, OH, OR, (CH<SUB>2</SUB>)<SUB>n2</SUB>OH, (CH<SUB>2</SUB>)<SUB>n1</SUB>OR, COOH, COOR, (CH<SUB>2</SUB>)<SUB>n2</SUB>COOH, (CH<SUB>2</SUB>)<SUB>n1</SUB>COOR, SR, S(OR), SO<SUB>2</SUB>R, NO<SUB>2</SUB>, heteroaryl, C<SUB>1</SUB>-C<SUB>3</SUB> alkyl, cycloalkyl, heterocycloalkyl, (CH<SUB>2</SUB>)<SUB>n2</SUB>-alkyl, (COOH, NH<SUB>2</SUB>)-(CH<SUB>2</SUB>)<SUB>u1</SUB>-cyclopropyl-(CH<SUB>2</SUB>)<SUB>u2</SUB>-, CO-NH-alkyl, Ar, (CH<SUB>2</SUB>)<SUB>n2</SUB>-Ar, CO-NH-Ar; - R<SUB>3</SUB> to R<SUB>19</SUB> being H, OH, OR, (CH<SUB>2</SUB>)<SUB>n2</SUB>OH, (CH<SUB>2</SUB>)<SUB>n1</SUB>OR, COOH, COOR, (CH<SUB>2</SUB>)<SUB>n2</SUB>COOH, (CH<SUB>2</SUB>)<SUB>n1</SUB>COOR, C<SUB>1</SUB>-C<SUB>3</SUB> alkyl, cycloalkyl, (CH<SUB>2</SUB>)n1-alkyl, aryl, (CH<SUB>2</SUB>)n1-aryl, halogen, CF<SUB>3</SUB>, SO<SUB>3</SUB>H, (CH<SUB>2</SUB>)<SUB>x</SUB> PO<SUB>3</SUB>H<SUB>2</SUB>, with x = 0, 1 or 2, B(OH)<SUB>2</SUB> , Formula (III), NO<SUB>2</SUB> , SO<SUB>2</SUB>NH<SUB>2</SUB> , SO<SUB>2</SUB>NHR; SR, S(O)R, SO<SUB>2</SUB>R, benzyl; - M<SUB>1</SUB> is an alkylene or arylene group; - n1= 1, 2 or 3, n2= 1, 2 or 3, n3= 0, 1, 2 or 3 and n4= 1, 2 or 3, n5= 1,2 or 3, n6= 0 or 1, u1 and u2, identical or different = 0,1 or 2, with the proviso that Formula (I) does not represent the racemic (3R, S) and the enantiomeric form (3R) of 3 amino,3-carboxy-propyl-2'-carboxy-ethylphosphinic acid; 3 amino,3-carboxy-propyl- 4'carboxy,2'carboxy-butanoylphosphinic acid; 3 amino,3-carboxy-propyl- 2'carboxy-butanoylphosphinic acid; 3 amino,3-carboxy-propyl- 3'amino, 3'carboxy-propylylphosphinic acid; and 3 amino,3-carboxypropyl -7'amino-2', 7'-dicarboxyheptylphosphinic acid, said hypophosphorous acid derivatives being diasteroisomers or enantiomers. Application as drugs. |
