Patent ID: 6020334
Filing Date: 2000-02-01
Classification: C07D

Abstract:
A compound of the formula ##STR54## wherein A.sup.1 and A.sup.2 independently are a proton-accepting group or a group convertible into a proton-accepting group;D is a spacer having a 2- to 6-atomic chain optionally bonded through a hetero-atom and/or a 5- or 6-membered ring, provided that the 5- or 6-membered ring is, depending on its bonding position, counted as 2- or 3-atomic chain;R.sup.1 is a hydrogen atom or a hydrocarbon group;R.sup.2 is hydrogen atom or a residual group formed by removing --CH(NH.sub.2)COOH from an .alpha.-amino acid, or R.sup.1 and R.sup.2 may be combined to form a 5- or 6-membered ring; P is a spacer having a 1- to 10-atomic chain optionally bonded through a hetero-atom and/or a 5- or 6-membered ring, provided that the 5- or 6-membered ring is, depending on its bonding position, counted as 2- or 3-atomic chain;Y is an optionally esterified or amidated carboxyl group;and n is an integer of 0 to 8, or a salt thereof;wherein A.sup.1 and A.sup.2 are(1) an amino, amidino or guanidino group which may be substituted with C.sub.1-6 alkyl; C.sub.2-6 alkenyl; C.sub.2-6 alkynyl; C.sub.3-6 cycloalkyl; C.sub.6-14 aryl; C.sub.7-16 aralkyl; C.sub.1-4 alkyl substituted with carbamoyloxy optionally substituted with C.sub.1-4 alkyl, C.sub.2-5 alkanoyloxy or a 5-membered cyclic group containing, besides carbon atoms, 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom, or a 6-membered cyclic group containing, besides carbon atoms, 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom; C.sub.2-8 alkoxycarbonyl; C.sub.1-8 alkylaminocarbonyl; C.sub.2-8 alkoxycarbonyloxy; a 5-membered cyclic group containing, besides carbon atoms, 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom, or a 6-membered cyclic group, besides carbon atoms, 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom, in the case where two or more substituents of the amino, amidino or guanidino group exist, they may be combined to form a 5- or 6-membered heterocyclic group,(2) an amidoxime group which may be substituted on the oxygen atom with C.sub.1-4 alkyl; C.sub.2-5 alkanoyl; benzoyl; C.sub.1-4 alkoxycarbonyl; C.sub.1-4 alkylthiocarbonyl; C.sub.2-5 alkanoyloxycarbonyl; benzoyloxycarbonyl; C.sub.6-12 aryloxycarbonyl or C.sub.7-14 aralkyloxycarbonyl which may be substituted with cyano, nitro, amino, C.sub.1-4 alkoxycarbonyl, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, mono- or di- C.sub.1-4 alkylamino, hydroxy, amido or C.sub.1-4 alkylthio; C.sub.6-12 aryl-carbonyl which may be substituted with C.sub.1-4 alkyl, C.sub.2-4 alkenyl or C.sub.2-4 alkynyl; carbamoyl which may be substituted with cyano, nitro, amino, C.sub.1-4 alkoxycarbonyl, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, mono- or di- C.sub.1-4 alkylamino, hydroxy, amido or C.sub.1-4 alkylthio or(3) an oxadiazolyl or thiadiazolyl group which may be substituted with oxo; thioxo; hydroxy; amino; mono- or di- C.sub.1-4 alkylamino; halogen; cyano; azido; C.sub.1-4 alkyl optionally substituted with halogen; C.sub.1-4 alkoxy; C.sub.1-4 alkylthio; C.sub.1-4 alkoxy-carbonyl; C.sub.1-4 alkylcarbamoyl; C.sub.6-12 aryl optionally substituted with cyano, nitro, amino, C.sub.1-4 alkoxycarbonyl, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, mono- or di- C.sub.1-4 alkylamino, hydroxy, amido or C.sub.1-4 alkylthio; or C.sub.7-14 aralkyl optionally substituted with cyano, nitro, amino, C.sub.1-4 alkoxycarbonyl, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, mono- or di- C.sub.1-4 alkylamino, hydroxy, amido or C.sub.1-4 alkylthio,D is a 2- to 6-membered chain optionally bonded through a hetero-atom and/or a 5- or 6-membered carbocyclic ring or the 5- or 6-membered heterocyclic ring containing 1 to 4 hetero-atoms selected from N, O and S, provided that the 5- or 6-membered carbocyclic ring or the 5- or 6-membered heterocyclic ring containing 1 to 4 hetero-atoms selected from N, O and S is, depending on its bonding position, counted as 2- or 3-membered chain,R.sup.1 is a hydrogen atom, a C.sub.1-6 alkyl group, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group, a C.sub.3-6 cycloalkyl group, a C.sub.6-14 aryl group or a C.sub.7-16 aralkyl group,R.sup.2 is a hydrogen atom; a C.sub.1-4 alkyl group; a C.sub.1-4 alkyl group substituted with phenyl which may be substituted with C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen or hydroxy; a C.sub.1-4 alkyl group substituted with hydroxy; or a C.sub.1-4 alkyl group substituted with carbamoyl, or R.sub.1 and R.sub.2 may be combined to form: ##STR55## Y is a group of the formula: ##STR56## wherein R.sup.5 and R.sup.6 independently are hydrogen, a C.sub.1-6 alkyl group; a C.sub.2-8 alkenyl group; a C.sub.1-4 alkyl group substituted with a 5-membered cyclic group containing, besides carbon atoms, 1 to 4 hetero-atoms selected from, oxygen atom, sulfur atom and nitrogen atom, or, a 6-membered cyclic group containing, besides carbon atoms, 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom, or a C.sub.6-12 aralkyl group which may be substituted with nitro, halogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, or, a group of the formula: ##STR57## wherein R.sup.7 is 1) hydroxyl group, 2) a C.sub.1-8 alkoxy, C.sub.2-12 alkenyloxy or benzyloxy group which may substituted with hydroxyl, amino, N--C.sub.1-4 alkylamino, N,N-di-C.sub.1-4 alkylamino, piperidino, morpholino, halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.1-4 alkoxycarbonyl, or 5-methyl-2-oxo-1,3-dioxolen-4-yl or 3) a group of the formula: --OCH(R.sup.7a)OCOR.sup.8 in which R.sup.7a is hydrogen, a C.sub.1-6 alkyl group or a C.sub.5-7 cycloalkyl group, and R.sup.8 is i) a C.sub.1-6 alkyl group, ii) a C.sub.2-8 alkenyl group, iii) a C.sub.5-7 cycloalkyl, iv) C.sub.1-3 alkyl group substituted with C.sub.5-7 cycloalkyl or C.sub.6-12 aryl optionally substituted with nitro, halogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, v) a C.sub.2-3 alkenyl group substituted with C.sub.5-7 cycloalkyl or C.sub.6-12 aryl, vi) a C.sub.6-12 aryl optionally substituted with nitro, halogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, vii) a C.sub.2-6 alkoxy group, viii) a C.sub.1-6 alkenyloxy group, ix) a C.sub.5-7 cycloalkyloxy group, x) a C.sub.1-3 alkoxy group substituted with C.sub.5-7 cycloalkyl or C.sub.6-12 aryl optionally substituted with nitro, halogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, xi) a C.sub.2-3 alkenyloxy group substituted with C.sub.5-7 cycloalkyl or C.sub.6-12 aryl optionally substituted with nitro, halogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, or xii) a C.sub.6-12 aryloxy group optionally substituted with nitro, halogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, and n is an integer of 0 to 8;wherein P is a group of the formula:--Z--B--in which z is ##STR58## in which right bond is bonded to B, or a bond: and B is ##STR59## in which a is an integer of 0 to 2, b is an integer of 0 to 2 and c is an integer of 1 to 5, or (ii) a bond.