1,4-diamino-2,3-dihydroxybutanes

There is provided by this invention a compound of the formula:

• ##STR188## wherein:
• R.sup.1 through R.sup.7 through R.sup.10 are independently selected from the following groups:
• hydrogen;
• C.sub.1 -C.sub.8 alkyl substituted with 0-3 R.sup.11 ;
• C.sub.2 -C.sub.8 alkenyl substituted with 0-3 R.sup.11 ;
• C.sub.3 -C.sub.8 alkynyl substituted with 0-3 R.sup.11 ;
• C.sub.3 -C.sub.8 cycloalkyl substituted with 0-3 R.sup.11 ;
• C.sub.6 -C.sub.10 bicycloalkyl substituted with 0-3 R.sup.11 ;
• aryl substituted with 0-3 R.sup.12 ;
• a C.sub.6 -C.sup.14 carbocyclic residue substituted with 0-3 R.sup.12 ;
• a heterocyclic ring system substituted with 0-2 R.sup.12 selected from pyridyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, benzothiophenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, or decahydroisoquinolinyl;
• R.sup.2A through R.sup.4A and R.sup.7A are independently selected from the following groups:
• hydrogen;
• C.sub.1 -C.sub.4 alkyl substituted with halogen or C.sub.1 -C.sub.2 alkoxy;
• benzyl substituted with halogen or C.sub.1 -C.sub.2 alkoxy;
• R.sup.5 and R.sup.6 are independently selected from the following groups:
• hydrogen:
• C.sub.1 -C.sub.6 alkoxycarbonyl;
• C.sub.1 -C.sub.6 alkylcarbonyl;
• benzoyl;
• phenoxycarbonyl;
• or
• phenylaminocarbony;
• wherein said alkyl residues are substituted with 0-3 R.sup.11, and said aryl residues are substituted with 0-3 R.sup.12 ;
• or any other group that, when administered to a mammalian subject, cleaves to form the original diol in which R.sup.5 and R.sup.6 are hydrogen;
• R.sup.11 is selected from one or more of the following:
• keto, halogen, cyano, --NR.sup.13 R.sup.14, --CO.sub.2 R.sup.13, --OC(.dbd.O)R.sup.13, --OR.sup.13, C.sub.2 -C.sub.6 alkoxyalkyl, --S(O).sub.m R.sup.13, --NHC(.dbd.NH)NHR.sup.13, --C(.dbd.NH)NHR.sup.13, --C(.dbd.O)NR.sup.13 R.sup.14, --NR.sup.14 C(.dbd.O)R.sup.13 --, NR.sup.14 C(.dbd.O)OR.sup.14, OC(.dbd.O)NR.sup.13 R.sup.14, --NR.sup.13 C(.dbd.O)NR.sup.13 R.sup.14, --NR.sup.14 SO.sub.2 NR.sup.13 R.sup.14, --NR.sup.14 SO.sub.2 R.sup.13, --SO.sub.2 NR.sup.13 R.sup.14, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.3 -C.sub.6 cycloalkylmethyl;
• a C.sub.5 -C.sub.14 carbocyclic residue substituted with 0-3 R.sup.12 ;
• aryl substituted with 0-3 R.sup.12 ;
• or a heterocyclic ring system substituted with 0-2 R.sup.12 selected from pyridyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, benzothiophenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, or decahydroisoquinolinyl;
• R.sup.12, when a substituent on carbon, is selected from one or more of the following:
• phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.3 -C.sub.6 cycloalkylmethyl, C.sub.7 -C.sub.10 arylalkyl, alkoxy, --NR.sup.13 R.sup.14, C.sub.2 -C.sub.6 alkoxyalkyl, C1-C4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 haloalkoxy, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4 alkylcarbonyloxy, C.sub.1 -C.sub.4 alkylcarbonyl, C.sub.1 -C.sub.4 alkylcarbonylamino, --S(O).sub.m R.sup.13, --SO.sub.2 NR.sup.13 R.sup.14, --NHSO.sub.2 R.sup.14 ;
• or R.sup.12 may be a 3- or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5- or 6-membered ring, said 5- or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, hydroxy, or NR.sup.13 R.sup.14 ;
• or, when R.sup.12 is attached to a saturated carbon atom it may be carbonyl or thiocarbonyl;
• and R.sup.12, when a substituent on nitrogen, is selected from one or more of the following:
• phenyl, benzyl, phenethyl, hydroxy, C.sub.1 -C.sub.4 hydroxyalkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.3 -C.sub.6 cycloalkylmethyl, --NR.sup.13 R.sup.14, C.sub.2 -C.sub.6 alkoxyalkyl, C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4 alkylcarbonyloxy, C.sub.1 -C.sub.4 alkylcarbonyl,
• R.sup.13 is H, phenyl, benzyl or C.sub.1 -C.sub.6 alkyl;
• R.sup.14 is H or C.sub.1 -C.sub.4 alkyl;
• or R.sup.13 R.sup.14 can join to form (CH.sub.2).sub.4, (CH.sub.2).sub.5, (CH.sub.2 CH.sub.2 N(R.sup.15)CH.sub.2 CH.sub.2), or (CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2);
• R.sup.15 is H or CH.sub.3 ;
• m is 0, 1 or 2;
• n and n.sup.1 are independently 0 or 1;
• W and W1 are independently selected from the following:
• --NR.sup.16 C(.dbd.Q)NR.sup.16 ;
• --C(.dbd.Q)NR.sup.16 --;
• --C(.dbd.Q)O--;
• --NR.sup.16 C(.dbd.Q)O--;
• --OC(.dbd.Q)NR.sup.16 --;
• --NR.sup.16 C(.dbd.Q)--;
• --C(.dbd.Q)--;
• --C(.dbd.Q)CH.sub.2 --;
• --NR.sup.16 SO.sub.2 NR.sup.16 --
• --NR.sup.16 SO.sub.2 --
• --SO.sub.2 NR.sup.16 --
• --SO.sub.2 --;
• --QCH.sub.2 --;
• --Q--;
• --(CH.sub.2).sub.p NR.sup.16 --;
• --CH.sub.2 CH.sub.2 --;
• --CH.dbd.CH--;
• --CH(OH)CH(OH)--;
• --CH(OH)CH.sub.2 --;
• --CH.sub.2 CH(OH)--;
• --CH(OH)--;
• --NH--NH--;
• --C(.dbd.O)NH--NH--;
• --C(Cl).dbd.N--;
• --C(--OR.sup.16).dbd.N--;
• --C(--NR.sup.16 R.sup.17).dbd.N--;
• --OP(.dbd.O)(Q.sup.1 R.sup.16)O--;
• --P(.dbd.O)(Q.sup.1 R.sup.16)O--;
• --SO.sub.2 NHC(.dbd.O)NH--;
• X and X.sup.1 are independently selected from the following:
• --C(.dbd.Q)NR.sup.16 --;
• --C(.dbd.Q)O--;
• --C(.dbd.Q)--;
• --CH.sub.2 C(.dbd.Q)--;
• --CH.sub.2 C(.dbd.Q)CH.sub.2 --;
• --C(.dbd.Q)CH.sub.2 --;
• --SO.sub.2 NR.sup.16 --
• --SO.sub.2 --;
• --CH.sub.2 QCH.sub.2 --;
• --CH.sub.2 Q--;
• --CH.sub.2 NR.sup.16 --;
• --CH.sub.2 CH.sub.2 --;
• --CH.dbd.CH--;
• --CH(OH)CH(OH)--;
• --CH(OH)CH2--;
• --CH.sub.2 CH(OH)--;
• --CH(OH)--;
• --C(.dbd.O)NH--NH--;
• --C(--OR.sup.16).dbd.N--;
• --C(--NR.sup.16 R.sup.17).dbd.N--;
• --C(L).dbd.N--;
• Y and Y.sup.1 are independently selected from the following:
• --C(.dbd.Q)NR.sup.16 --;
• --(CH.sub.2).sub.p C(.dbd.Q)NR.sup.16 --;
• --SO.sub.2 NR.sup.16 --;
• --CH2NR.sup.16 --;
• --C(L).dbd.N--;
• --C(--OR.sup.16).dbd.N--;
• --C(--NR.sup.16 R.sup.17).dbd.N--;
• --NR12C(.dbd.O)NR.sup.16 --;
• --(CH.sub.2).sub.p NR12C(.dbd.O)NR.sup.16 ;
• --OC(.dbd.O)NR.sup.16 --;
• --(CH.sub.2).sub.p OC(.dbd.O)NR.sup.16 --;
• R.sup.16 is H, benzyl or C.sub.1 -C.sub.4 alkyl;
• R.sup.17 is H or C.sub.1 -C.sub.4 alkyl;
• p is 1 or 2;
• Q is selected from oxygen or sulfur;
• Q.sup.1 is selected from oxygen, sulfur, NR.sup.14 or a direct bond;
• and pharmaceutically acceptable salts and prodrugs thereof.