Claims
- 1. A phosphonosulfonate, or the pharmaceutically-acceptable salt or ester thereof, according to formula (I): ##STR88## wherein (A)
- (1) A is selected from the group consisting of SR.sup.1 ; R.sup.2 SR.sup.1 ; amino; hydroxy;
- (2) B is
- (a) --NH.sub.2 ;
- (b) a saturated or unsaturated C.sub.1 -C.sub.15 alkyl chain substituted with one or more substituents selected from the group consisting of R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 �N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ;
- (c) a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is nitrogen; and where said heteroalkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (d) a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is selected from S and 0; and where said heteroalkyl chain is substituted with one or more substituents selected from the group consisting of --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R4; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ; or
- (e) R.sup.6 --L-- where
- (i) L is selected from the group consisting of covalent bond; N; --N(R.sup.5).sub.2.sup.+ ; S; O; a saturated or unsaturated C.sub.1 -C.sub.15 alkyl chain, where said alkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amine, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is N, S, or O, and where said heteroalkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amine, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and
- (ii) R.sup.6 is selected from the group consisting of saturated monocyclic or polycyclic carbocyclic rings; unsaturated monocyclic or polycyclic carbocyclic rings; saturated monocyclic or polycyclic heterocyclic rings and unsaturated monocyclic or polycyclic heterocyclic rings wherein R.sup.6 is unsubstituted or is substituted with one or more substituents independently selected from the group consisting of hydrogen; --R.sup.3 SR.sup.1 ; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; --R.sup.3 OR.sup.4 ; --R.sup.3 CO.sub.2 R.sup.4 ; R.sup.3 O.sub.2 CR.sup.4 ; --R.sup.3 N(R.sup.4).sub.2 ; R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; --R.sup.3 C(O)N(R.sup.4).sub.2 ; halogen; --R.sup.3 C(O)R.sup.4 ; arylalkyl; nitro; unsubstituted aryl or aryl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and hydroxy; and
- (3)
- (a) R.sup.1 is independently selected from the group consisting of hydrogen; --C(O)R.sup.7 ; C(S)R.sup.7 ; --C(O)N(R.sup.7).sub.2 ; --C(O)OR.sup.7 ; --C(S)N(R.sup.7).sub.2 ; and --C(S)OR.sup.7 ; where R.sup.7 is hydrogen or unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted win one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (b) R.sup.2 is unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (c) R.sup.3 is selected from the group consisting of covalent bond and unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (d) R.sup.4 is independently selected from the group consisting of hydrogen; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and --R.sup.2 SR.sup.1 ; and
- (e) R.sup.5 is independently selected from the group consisting of unsubstituted C.sub.1 -C.sub.15 alkyl or C.sub.1 -C.sub.15 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl; or alkynyl; unsubstituted phenyl or phenyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; benzyl; and --R.sup.2 SR.sup.1 ;
- or
- A and B are covalently linked together with C* to form a monocyclic ring of formula (a); or a bicyclic ring of formula (b): ##STR89## where (1) W is a saturated or unsaturated carbocyclic ring formed by C*, X, and X', said carbocyclic ring having a total of from 3 to 6 ring carbon atoms, where said carbocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; or a saturated or unsaturated heterocyclic ring formed by C*, X, and X', said heterocyclic ring having a total of from 4 to 6 ring atoms, where one or more of said ring atoms is N, O, or S, and where said heterocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (2) V is a saturated or unsaturated carbocyclic ring formed by X and X', said carbocyclic ring having a total of from 3 to 8 ring carbon atoms, and where said carbocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; or a saturated or unsaturated heterocyclic ring formed by X and X', said heterocyclic ring having a total of from 3 to 8 ring atoms, where one or more of said ring atoms is N, O, or S, and where said heterocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and
- (3) X and X' are independently N or C; except that if neither V nor W is a nitrogen containing heterocycle, then at least one of V or W is substituted with one or more substituents selected from the group consisting of --R.sup.3 N(R.sup.4).sub.2 ; R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ;
- and wherein R is selected from the group consisting of hydrogen, lower alkyl, lower acyloxyalkyl, aminocarbonyloxyalkyl, pivaloyloxymethyl, lactonyl, lower alkoxyacyloxyalkyl, alkoxyalkyl, choline and acylamino alkyl; or
- (C)
- (1) A is selected from the group consisting of hydrogen; halogen; SR.sup.1 ; R.sup.2 SR.sup.1 ; amino; hydroxy; and unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (2) B is a radical which contains less than 7 carbons wherein B is chosen from;
- (a) --NH.sub.2 ;
- (b) a saturated or unsaturated C.sub.1 -C.sub.6 alkyl chain substituted with one or more substituents selected from the group consisting of --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ;
- (c) a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is nitrogen; and where said heteroalkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (d) a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is selected from S and O; and where said heteroalkyl chain is substituted with one or more substituents selected from the group consisting of --R.sup.3 N(R.sup.4).sub.2 ; R.sup.3 N(R.sup.4)C(O)R4; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ; or
- (e) R.sup.6 --L-- where
- (i) L is selected from the group consisting of covalent bond; N; S; O; a saturated or unsaturated C.sub.1 -C.sub.5 alkyl chain, where said alkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is N, S, or O, and where said heteroalkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and
- (ii) R.sup.6 is selected from the group consisting of saturated monocyclic rings; unsaturated monocyclic carbocyclic rings; saturated monocyclic or polycyclic heterocyclic rings and unsaturated monocyclic or polycyclic heterocyclic rings wherein R.sup.6 is unsubstituted or is substituted with one or more substituents independently selected from the group consisting of hydrogen; --R.sup.3 SR.sup.1 ; unsubstituted C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.5 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; --R.sup.3 OR.sup.4 ; R.sup.3 CO.sub.2 R.sup.4 ; --R.sup.3 O.sub.2 CR.sup.4 ; --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; --R.sup.3 C(O)N(R.sup.4).sub.2 ; halogen; --R.sup.3 C(O)R.sup.4 ; arylalkyl; nitro; unsubstituted aryl or aryl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and hydroxy; and
- (3)
- (a) R.sup.1 is independently selected from the group consisting of hydrogen; --C(O)R.sup.7 ; --C(S)R.sup.7 ; --C(O)N(R.sup.7).sub.2 ; --C(O)OR.sup.7 ; --C(S)N(R.sup.7).sub.2 ; and --C(S)OR.sup.7 ; where R.sup.7 is hydrogen or unsubstituted C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkyl substituted win one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (b) R.sup.2 is unsubstituted C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (c) R.sup.3 is selected from the group consisting of covalent bond and unsubstituted C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.5 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (d) R.sup.4 is independently selected from the group consisting of hydrogen; unsubstituted C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.5 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and --R.sup.2 SR.sup.1; and
- (e) R.sup.5 is independently selected from the group consisting of unsubstituted C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.5 alkyl substituted with one or more of alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; unsubstituted phenyl or phenyl substituted with one or more of hydroxy, oxo, thioxo, amino, amidinoalkyl, halo, thio; or
- (D)
- (1) A is selected from the group consisting of hydrogen; halogen; SR.sup.1 ; R.sup.2 SR.sup.1 ; amino; hydroxy; and unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (2) B is selected from charged radicals selected from the group consisting of;
- (b) a saturated or unsaturated C.sub.1 -C.sub.15 alkyl chain substituted with one or more substituents selected from the group consisting of --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ;
- (c) a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is nitrogen; and where said heteroalkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; wherein the chain with its substituents, if any, must be charged;
- (d) a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is selected from S and O; and where said heteroalkyl chain is substituted with one or more substituents selected from the group consisting of --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ; wherein the chain with its substituents, if any, must be charged;
- (e) R.sup.6 --L--; wherein R.sup.6 --L-- with its substituents, if any, must be charged; where
- (i) L is selected from the group consisting of covalent bond; N; --N(R.sup.5).sub.2.sup.+ ; S; O; a saturated or unsaturated C.sub.1 -C.sub.15 alkyl chain, where said alkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is N, S, or O, and where said heteroalkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and
- (ii) R.sup.6 is selected from the group consisting of saturated monocyclic or polycyclic carbocyclic rings; unsaturated monocyclic or polycyclic carbocyclic rings; saturated monocyclic or polycyclic heterocyclic rings and unsaturated monocyclic or polycyclic heterocyclic rings wherein R.sup.6 is unsubstituted or is substituted with one or more substituents independently selected from the group consisting of hydrogen; --R.sup.3 SR.sup.1 ; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; --R.sup.3 OR.sup.4 ; --R.sup.3 CO.sub.2 R.sup.4 ; --R.sup.3 O.sub.2 CR.sup.4 ; --R.sup.3 N(R.sup.4).sub.2 ; R.sup.3 �--N(R.sup.5)3!+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; --R.sup.3 C(O)N(R.sup.4).sub.2 ; halogen; --R.sup.3 C(O)R.sup.4 ; arylalkyl; nitro; unsubstituted aryl or aryl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and hydroxy; and
- (3)
- (a) R.sup.1 is independently selected from the group consisting of hydrogen; --C(O)R.sup.7 ; C(S)R.sup.7 ; --C(O)N(R.sup.7).sub.2 ; --C(O)OR.sup.7 ; --C(S)N(R,7).sub.2 ; and --C(S)OR.sup.7 ; where R.sup.7 is hydrogen or unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted win one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylallcyl, or alkynyl;
- (b) R.sup.2 is unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (c) R.sup.3 is selected from the group consisting of covalent bond and unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (d) R.sup.4 is independently selected from the group consisting of hydrogen; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and --R.sup.2 SR.sup.1 ; and
- (e) R.sup.5 is independently selected from the group consisting of unsubstituted C.sub.1 -C.sub.15 alkyl or C.sub.1 -C.sub.15 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; unsubstituted phenyl or phenyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; benzyl; and --R.sup.2 SR.sup.1.
- 2. A compound according to claim 1, wherein A is hydroxy; and wherein B is a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is nitrogen, and where said heteroalkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; or B is R.sup.6 --L--.
- 3. A compound according to claim 1 wherein B is R.sup.6 --L--.
- 4. A compound according to claim 3, wherein L is covalent bond, N,N(R.sup.5).sub.2 .sup..+-., a C.sub.1 -C.sub.15 alkyl chain, or a nitrogen containing heteroalkyl chain having from 2 to 15 chain atoms.
- 5. A compound according to claim 4, wherein L is a C.sub.1 -C.sub.15 alkyl chain.
- 6. A compound according to claim 5, wherein said C.sub.1 -C.sub.15 alkyl chain is substituted with one or more substituents selected from the group consisting of --R.sup.3 SR.sup.1 ; hydrogen; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; --R.sup.3 OR.sup.4 ; and --R.sup.3 CO.sub.2 R.sup.4.
- 7. A compound according to claim 4, wherein L is a nitrogen containing heteroalkyl chain having from 2 to 15 chain atoms.
- 8. A compound according to claim 7, wherein said nitrogen containing heteroalkyl chain is substituted with one or more substituents selected from the group consisting of --R.sup.3 SR.sup.1 ; hydrogen; --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 �N(R.sup.5).sub.3 !+; and --R.sup.3 N(R.sup.4)C(O)R.sup.4.
- 9. A compound according to claim 3, wherein R.sup.6 is a monocyclic heterocyclic moiety.
- 10. A compound according to claim 9, wherein R.sup.6 is a six-membered heterocyclic ring moiety selected from the group consisting of pyridine, pyrridine, piperidine, pyridinium, pyrimidinium, and piperidinium; or R.sup.6 is a five-membered heterocyclic ring moiety selected from the group consisting of imidazol, pyrrole, pyrrolidine, imidazolium, pyrrolium, and pyrrolidinium.
- 11. A compound according to claim 3, wherein R.sup.6 is a polycyclic heterocyclic moiety.
- 12. A compound according to claim 11, wherein R.sup.6 is a six-membered ring fused to a five-membered ring, said polycyclic heterocycle being selected from the group consisting of indol, indolium, pyrindine, imidazol-(1,2-a-)pyridine, imidazol-(1,2-a-)pyridinium, and pyrindinium; or R.sup.6 is a six-membered ring fused to a six-membered ring, said polycyclic heterocycle being selected from the group consisting of quinoline, isoquinoline, tetrahydroquinoline, octahyrdroquinoline, quinolinium, isoquinolinium, tetrahydroquinolinium, or octahydroquinolinium.
- 13. A compound according to claim 3, wherein R.sup.6 is a monocyclic carbocyclic moiety.
- 14. A compound according to claim 13, wherein R.sup.6 is cycloheptyl or cyclohexyl.
- 15. A compound according to claim 3, wherein R.sup.6 is substituted with one or more substituents selected from the group consisting of hydrogen; --R.sup.3 SR.sup.1 ; --R.sup.3 N(R.sup.4).sub.2 ; R.sup.3 �--N(R.sup.5).sub.3 !+; and --R.sup.3 N(R.sup.4)C(O)R.sup.4.
- 16. A compound according to claim 2, wherein B is a heteroalkyl chain having from 2 to 15 chain atoms where one or more chain atoms is nitrogen.
- 17. A compound according to claim 16, wherein said heteroalkyl chain is substituted with one or more substituents selected from the group consisting of --R.sup.3 SR.sup.1 ; hydrogen; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; --R.sup.3 OR.sup.4 ; --R.sup.3 CO.sub.2 R.sup.4 ; --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 �N(R.sup.5).sub.3 !+; and --R.sup.3 N(R.sup.4)C(O)R.sup.4.
- 18. A compound according to claim 2, wherein R.sup.4 is hydrogen.
- 19. A compound according to claim 2, wherein R.sup.1 is hydrogen; --C(O)R.sup.7 ; C(S)R.sup.7 ; or C(O)N(R.sup.7).sub.2.
- 20. A compound according to claim 1, wherein A and B, together with C*, form a bicyclic ring, where both and X and X' are carbon atoms.
- 21. A compound according to claim 20, wherein W is a five-membered carbocyclic ring comprising C*, X, and X'.
- 22. A compound according to claim 21, wherein V is a five-membered ring or a six-membered ring.
- 23. A compound according to claim 22, wherein V is a heterocycle containing at least one ring nitrogen atom.
- 24. A compound according to claim 20, wherein said bicyclic ring is substituted with one or more substituents selected from the group consisting of --R.sup.3 SR.sup.1 ; hydrogen; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; --R.sup.3 OR.sup.4 ; --R.sup.3 CO.sub.2 R.sup.4 ; --R.sup.3 O.sub.2 CR.sup.4 ; --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 �N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2.
- 25. A compound according to claim 24, wherein said bicyclic ring is substituted with one or more of --R.sup.3 SR.sup.1 ; hydrogen; --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 CO.sub.2 R.sup.4 ; --R.sup.3 �N(R.sup.5).sub.3 !+; or --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; and R.sup.4 is R.sup.3 SR.sup.1 or hydrogen.
- 26. A compound according to claim 25, wherein R.sup.1 is hydrogen; --C(O)R.sup.7 ; --C(S)R.sup.7 ; or --C(O)N(R.sup.7).sub.2.
- 27. A phosphonosulfonate, or the pharmaceutically-acceptable salt or ester thereof, according to formula (I) ##STR90## wherein (A)
- (1) A is hydroxy; and
- (2) B is ##STR91## wherein (a) m is an integer from 0 to 10; n is an integer from 0 to 10; and m+n is an integer from 0 to 10;
- (b) R.sup.8 is independently selected from the group consisting of covalent bond; R.sup.3 SR.sup.1 ; hydrogen; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; --R.sup.3 OR.sup.4 ; --R.sup.3 CO.sub.2 R.sup.4 ; --R.sup.3 O.sub.2 CR.sup.4 ; --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 �N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; --R.sup.3 C(O)N(R.sup.4).sub.2 ; halogen; --R.sup.3 C(O)R.sup.4 ; nitro; hydroxy; a saturated monocyclic or polycyclic carbocyclic ring, wherein said carbocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl or alkynyl; an unsaturated monocyclic or polycyclic carbocyclic ring, wherein said carbocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, arloxy, arylalkyl, or alkynyl; a saturated monocyclic or polycyclic heterocyclic ring, where said heterocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary. aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and an unsaturated monocyclic or polycyclic heterocyclic ring, where said heterocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (c) R.sup.1 is independently selected from the group consisting of hydrogen; --C(O)R.sup.7 ; --C(S)R.sup.7 ; --C(O)N(R.sup.7).sub.2 ; --C(O)OR.sup.7 ; --C(S)N(R.sup.7).sub.2 ; and --C(S)OR.sup.7 ; where R.sup.7 is hydrogen or unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy. alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (d) R.sup.3 is selected from the group consisting of covalent bond and unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (e) R.sup.4 is independently selected from the group consisting of hydrogen; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and --R.sup.2 SR.sup.1 ;
- (f) R.sup.5 is independently selected from the group consisting of unsubstituted C.sub.1 -C.sub.35 alkyl or C.sub.1 -C.sub.35 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; unsubstituted phenyl or phenyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; benzyl; and --R.sup.2 SR.sup.1 ;
- (g) L is selected from the group consisting of covalent bond; --N(R.sup.8)--; �--N(R.sup.5).sub.2 --!+; --S--; --0--; and --D--C(.dbd.E)--S--, where D is selected from the group consisting of covalent bond, O, or S, and E is O or S; and wherein
- (i) when L is --N(R.sup.8)--, or when L is �--N(R.sup.5).sub.2 --!+ and m is an integer from 1 to 10, R.sup.9 is independently selected from the group consisting of covalent bond; hydrogen; unsubstituted C.sub.1 -C.sub.35 alkyl or C.sub.1 -C.sub.35 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; R.sup.2 SR.sup.1 ; and R.sup.10 ;
- (ii) when L is �--N(R.sup.5).sub.2 --!+ and m=0, R.sup.9 is selected from the group consisting of unsubstituted C.sub.1 -C.sub.35 alkyl or C.sub.1 -C.sub.35 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; R.sup.2 SR.sup.1 ; and R.sup.10 ; or
- (iii) when L is covalent bond, --S--, --O--, or --D--C(.dbd.E)--S, R.sup.9 is R.sup.10.
- (h) R.sup.10 is a saturated, unsaturated, or aromatic monocyclic or polycyclic carbocycle or a saturated, unsaturated, or aromatic monocyclic or polycyclic heterocycle containing one or more heteroatoms; where said carbocycle or heterocycle is substituted with one or more R.sup.11 substituents; and
- (i) each R.sup.11 is independently selected from the group consisting of --R.sup.3 SR.sup.1 ; hydrogen; substituted or unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; --R.sup.3 OR.sup.4 ; --R.sup.3 CO.sub.2 R.sup.4 ; --R.sup.3 O.sub.2 CR.sup.4 ; --R.sup.3 N(R.sup.4).sub.2 ; R.sup.3 �--N(R.sup.5)3!+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; --R.sup.3 C(O)N(R.sup.4).sub.2 ; halogen; --R.sup.3 C(O)R.sup.4 ; hydroxy; unsubstituted arylalkyl or arylalkyl substituted with one or more of alkyl, alkenyl, alkoxy. hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; nitro; and unsubstituted aryl or aryl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- or
- (B) A and B are covalently linked together with C* to form a monocyclic or bicyclic ring having the following structure: ##STR92## wherein (a) A and B are independently selected from the group consisting of covalent bond, --O--, --S--, and --NR.sup.10 --;
- (b) Q is selected from the group consisting of covalent bond; --NR.sup.12 --; and �--N(R.sup.13).sub.2 --!+;
- (c) X and X' are independently selected from C(R.sup.12) or N;
- (d) each R.sup.12 is independently selected from the group consisting of --R.sup.3 SR.sup.1 ; hydrogen; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloallcyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; --R.sup.3 OR.sup.4 ; --R.sup.3 CO.sub.2 R.sup.4 ; --R.sup.3 O.sub.2 CR.sup.4 ; --R.sup.3 N(R.sup.4).sub.2 ; R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 C(O)N(R.sup.4).sub.2 ; halogen; --R.sup.3 C(O)R.sup.4 ; hydroxy; unsubstituted arylalkyl or arylalkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; nitro and unsubstituted aryl or aryl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and
- (e) each R.sup.13 is selected from the group consisting of covalent bond unsubstituted C.sub.1 -C.sub.35 alkyl or C.sub.1 -C.sub.35 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl halo carboxy, alkoacetyl thio, thiol, aryl cycloalkyl, heteroaryl heterocloalkyl, imino, hydroxylalkyl aryloxy, arylalkyl, or alkynyl; unsubstituted phenyl or phenyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkenyl; benzyl; and R.sup.2 SR.sup.1 ;
- (f) when Q is other than covalent bond, k and j and k+j are integers from 0 to 5; when Q is covalent bond, k and j and k+j are integers from 0 to 6; and
- (g) p and q and p+q are independently integers from 0 to 3; except that if Q is covalent bond, then at least one of R.sup.11 or R.sup.12 is selected from the group consisting of --R.sup.3 N(R.sup.4).sub.2 ; R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ;
- and wherein R is selected from the group consisting of hydrogen, lower alkyl, lower acyloxyalkyl, aminocarbonyloxyalkyl, pivaloyloxymethyl, lactonyl, lower alkoxyacyloxyalkyl, alkoxyalkyl, choline and acylamino alkyl.
- 28. A pharmaceutical composition comprising:
- (a) a safe and effective amount of a phosphonosulfonate compound according to claim 1; and
- (b) pharmaceutically-acceptable carriers.
- 29. A pharmaceutical composition comprising:
- (a) a safe and effective amount of a phosphono sulfonate compound according to claim 2; and
- (b) pharmaceutically-acceptable carriers.
- 30. A pharmaceutical composition comprising:
- (a) a safe and effective amount of a phosphonosulfonate compound according to claim 20; and
- (b) pharmaceutically-acceptable carriers.
- 31. A pharmaceutical composition comprising:
- (a) a safe and effective amount of a phosphonosulfonate compound according to claim 27; and
- (b) pharmaceutically-acceptable carriers.
- 32. A method for treating or preventing pathological conditions associated with abnormal calcium and phosphate metabolism in humans or other mammals in need of such treatment, comprising administering to a human or other mammal a safe and effective amount of a phosphonosulfonate compound of claim 1.
- 33. A method for treating or preventing pathological conditions associated with abnormal calcium and phosphate metabolism in humans or other mammals in need of such treatment, comprising administering to a human or other mammal a safe and effective amount of a phosphonosulfonate compound, or the pharmaceutically-acceptable salt or ester thereof, according to formula (I): ##STR93## wherein (A)
- (1) A is selected from the group consisting of hydrogen; halogen; SR.sup.1 ; R.sup.2 SR.sup.1 ; amino; hydroxy; and unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (2) B is
- (a) --NH.sub.2 ;
- (b) a saturated or unsaturated C.sub.1 -C.sub.15 alkyl chain substituted with one or more substituents selected from the group consisting of --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ;
- (c) a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is nitrogen; and where said heteroalkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (d) a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is selected from S and O; and where said heteroalkyl chain is substituted with one or more substituents selected from the group consisting of --R.sup.3 N(R.sup.4).sub.2 ; --R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ; or
- (e) R.sup.6 --L-- where
- (i) L is selected from the group consisting of covalent bond; N; --N(R.sup.5).sub.2.sup.+ ; S; O; a saturated or unsaturated C.sub.1 -C.sub.15 alkyl chain, where said alkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and a saturated or unsaturated heteroalkyl chain having from 2 to 15 chain atoms, where one or more of said chain atoms is N, S, or O, and where said heteroalkyl chain is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and
- (ii) R.sup.6 is selected from the group consisting of saturated monocyclic or polycyclic carbocyclic rings; unsaturated monocyclic or polycyclic carbocyclic rings; saturated monocyclic or polycyclic heterocyclic rings and unsaturated monocyclic or polycyclic heterocyclic rings wherein R.sup.6 is unsubstituted or is substituted with one or more substituents independently selected from the group consisting of hydrogen; --R.sup.3 SR.sup.1 ; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; --R.sup.3 OR.sup.4 ; --R.sup.3 CO.sub.2 R.sup.4 ; R.sup.3 O.sub.2 CR.sup.4 ; --R.sup.3 N(R.sup.4).sub.2 ; R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; --R.sup.3 C(O)N(R.sup.4).sub.2 ; halogen; --R.sup.3 C(O)R.sup.4 ; arylalkyl; nitro; unsubstituted aryl or aryl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and hydroxy; and
- (3)
- (a) R.sup.1 is independently selected from the group consisting of hydrogen; --C(O)R.sup.7 ; --C(S)R.sup.7 ; --C(O)N(R.sup.7).sub.2 ; --C(O)OR.sup.7 ; --C(S)N(R.sup.7).sub.2 ; and --C(S)OR.sup.7 ; where R.sup.7 is hydrogen or unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted win one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (b) R.sup.2 is unsubstituted C 1-C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (c) R.sup.3 is selected from the group consisting of covalent bond and unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (d) R.sup.4 is independently selected from the group consisting of hydrogen; unsubstituted C.sub.1 -C.sub.8 alkyl or C.sub.1 -C.sub.8 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and --R.sup.2 SR.sup.1 ; and
- (e) R.sup.5 is independently selected from the group consisting of unsubstituted C.sub.1 -C.sub.15 alkyl or C.sub.1 -C.sub.15 alkyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; unsubstituted phenyl or phenyl substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; benzyl; and --R.sup.2 SR.sup.1 ;
- or
- (B) A and B are covalently linked together with C* to form a monocyclic ring of formula (a); or a bicyclic ring of formula (b): ##STR94## where (1) W is a saturated or unsaturated carbocyclic ring formed by C*, X, and X', said carbocyclic ring having a total of from 3 to 6 ring carbon atoms, where said carbocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; or a saturated or unsaturated heterocyclic ring formed by C*, X, and X', said heterocyclic ring having a total of from 4 to 6 ring atoms, where one or more of said ring atoms is N, O, or S, and where said heterocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heteroeycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl;
- (2) V is a saturated or unsaturated carbocyclic ring formed by X and X', said carbocyclic ring having a total of from 3 to 8 ring carbon atoms, and where said carbocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; or a saturated or unsaturated heterocyclic ring formed by X and X', said heterocyclic ring having a total of from 3 to 8 ring atoms, where one or more of said ring atoms is N, O, or S, and where said heterocyclic ring is unsubstituted or is substituted with one or more of alkyl, alkenyl, alkoxy, hydroxy, oxo, thioxo, amino, aminoalkyl, cyano, quaternary amino, quaternary aminoalkyl, amidino, amidinoalkyl, halo, carboxy, alkoxyacetyl, thio, thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, imino, hydroxylalkyl, aryloxy, arylalkyl, or alkynyl; and
- (3) X and X' are independently N or C; except that if neither V nor W is a nitrogen containing heterocycle, then at least one of V or W is substituted with one or more substituents selected from the group consisting of --R.sup.3 N(R.sup.4).sub.2 ; R.sup.3 �--N(R.sup.5).sub.3 !+; --R.sup.3 N(R.sup.4)C(O)R.sup.4 ; --R.sup.3 N(R.sup.4)C(S)R.sup.4 ; --R.sup.3 N(R.sup.4)C(N)R.sup.4 ; and --R.sup.3 C(O)N(R.sup.4).sub.2 ;
- and wherein R is selected from the group consisting of hydrogen, lower alkyl, lower acyloxyalkyl, aminocarbonyloxyalkyl, pivaloyloxymethyl, lactonyl, lower alkoxyacyloxyalkyl, alkoxyalkyl, choline and acylamino alkyl.
Parent Case Info
This is a continuation-in-part of U.S. patent application Ser. Nos. 07/890,885, (abandoned) 07/891,487, (abandoned) 07/891,355, (abandoned) 07/891,490, (abandoned) 07/890,886, (abandoned) and 07/891,309, (abandoned) all filed May 29, 1992.
US Referenced Citations (9)
Foreign Referenced Citations (1)
Number |
Date |
Country |
0 477 454 A1 |
Apr 1992 |
EPX |
Continuation in Parts (1)
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Number |
Date |
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Parent |
890885 |
May 1992 |
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