Claims
- 1. Cyclic thio-substituted phosphonates, and the pharmaceutically-acceptable salts and esters thereof, having the following structure: ##STR35## wherein (a) X and Y are independently selected from nil, oxygen, sulfur, or nitrogen,
- (b) R is PO.sub.3 H.sub.2 or P(O)(OH)R.sup.4, wherein R.sup.4 is substituted or unsubstituted C.sub.1 -C.sub.8 alkyl;
- (c) m and n are integers from 0 to 5, and m+n equals 0 to 5;
- (d) p and q are integers from 0 to 3, and p+q equals 1 to 3;
- (e) s is an integer from 0 to 2 and when X is nil and m+n 0, s=2;
- (f) each R.sub.1 is independently selected from --SR.sup.6 ; R.sup.8 SR.sup.6 ; nil; hydrogen; unsubstituted or substituted C.sub.1 -C.sub.8 alkyl; unsubstituted or substituted aryl; hydroxy; amido; alkoxy; --CO.sub.2 R.sup.3 ; --O.sub.2 CR.sup.3 ; --NR.sup.3.sub.2 ; --N(R.sup.3)C(O)R.sup.3 ; --OR.sup.3 ; --C(O)N(R.sup.3).sub.2 ; substituted or unsubstituted benzyl; nitro; and combinations thereof;
- (g) R.sup.2 is one or more substituents of X and Y and is independently selected from the group consisting of --SR.sup.6 ; R.sup.8 SR.sup.6 ; nil; hydrogen; unsubstituted or substituted C.sub.1 -C.sub.8 alkyl; unsubstituted or substituted aryl; hydroxy; amido; --CO.sub.2 R.sup.3 ; --O.sub.2 CR.sup.3 ; --N(R.sup.3)C(O)R.sup.3 ; --OR.sub.3 ; --N(R.sup.3).sub.2 ; --C(O)N(R.sup.3).sub.2 ; substituted or unsubstituted benzyl; nitro; or combinations thereof;
- (h) R.sup.3 is independently selected from hydrogen; substituted or unsubstituted C.sub.1 -C.sub.8 alkyl; or R.sup.8 SR.sup.6 ;
- (i) R.sup.6 is H; --C(O)R.sup.7 ; --C(S)R.sup.7 ; C(O)N(R.sup.7).sub.2 ; C(S)N(R.sup.7).sub.2 ; C(O)OR.sup.7, or C(S)OR.sup.7 ; wherein R.sup.7 is hydrogen, or substituted or unsubstituted C.sub.1 -C.sub.8 alkyl;
- (j) R.sup.8 is substituted or unsubstituted C.sub.1 -C.sub.8 alkyl;
- (k) wherein any ring formed is of 4 to 7 members;
- provided that at least one of R.sup.1, R.sup.2, and R.sup.3 is SR.sup.6 or R.sup.8 SR.sup.6.
- 2. A compound according to claim 1, of formula: ##STR36## wherein the ring system is singly or multiply saturated or unsaturated;
- X is nitrogen;
- Y is CH.sub.2 or NH;
- R is geminal to the PO(OH).sub.2 and is SO.sub.3 H, COOH, PO(OH)R.sub.4 ; and R.sub.4 is a substituted or unsubstituted C.sub.1 to C.sub.8 alkyl;
- R.sub.1 is independently chosen from the group consisting of hydrogen, alkyl, thioalkyl, and alkyl thioalkyl;
- R.sub.2 is independently chosen from the group consisting of hydrogen, alkyl thio, thio alkyl, alkyl thioalkyl, alkoxy, hydroxy, amino, alkyl amino and dialkyl amino.
- 3. A compound according to claim 1, of formula: ##STR37## wherein the ring system is saturated or singly or multiply unsaturated;
- X is nitrogen;
- Y is CH.sub.2 or NH;
- R is geminal to the PO(OH).sub.2 and is chosen from the group consisting of SO.sub.3 H, COOH, PO(OH)R.sub.4 ; and R.sub.4 is a substituted or unsubstituted C.sub.1 to C.sub.8 alkyl;
- R.sub.1 is independently chosen from the group consisting of hydrogen, alkyl, thioalkyl, and alkyl thioalkyl;
- R.sub.2 is independently chosen from the group consisting of hydrogen, alkyl thio, thio alkyl, alkyl thioalkyl, alkoxy, hydroxy, amino, alkyl amino and dialkyl amino.
- 4. A compound according to claim 1, of formula: ##STR38## wherein the ring system is saturated or singly or multiply unsaturated to any degree;
- R is PO.sub.3 H.sub.2, PO(OH)R.sub.4 ; wherein R.sub.4 is a substituted or unsubstituted C.sub.1 to C.sub.8 alkyl;
- R.sub.1 is independently chosen from the group consisting of SR.sub.6, R.sub.8 SR.sub.6, hydrogen, alkyl, alkoxy hydrogen, amino, alkyl amino, dialkyl amino, amido, alkoxy carbonyl and alkenoyloxy;
- R.sub.2 is independently chosen from the group consisting of SR.sub.6, R.sub.8 SR.sub.6, hydrogen, alkyl, alkoxy hydrogen, amino, alkyl amino, dialkyl amino, amido, alkoxy carbonyl and alkenoyloxy.
- 5. A compound of formula: ##STR39## wherein the ring system is saturated or singly or multiply unsaturated;
- X is nitrogen;
- R is PO.sub.3 H.sub.2, PO(OH)R.sub.4 and R.sub.4 is a substituted or unsubstituted C.sub.1 to C.sub.8 alkyl;
- R.sub.1 is SR.sub.6, R.sub.4 SR.sub.6, hydrogen, alkyl, alkoxy hydrogen, amino, alkyl amino, dialkyl amino, amido, alkoxy carbonyl or alkenoyloxy;
- R.sub.2 is SR.sub.6, R.sub.4 SR.sub.6, hydrogen, alkyl, alkoxy hydrogen, amino, alkyl amino, dialkyl amino, amido, alkoxy carbonyl or alkenoyloxy;
- R.sub.6 is H, COR.sub.7, CSR.sub.7, CON(R.sub.7).sub.2, CSN(R.sub.7).sub.2, COOR.sub.7, CSOR.sub.7 ; wherein R.sub.7 is independently hydrogen or R.sub.4.
- 6. The compound of claim 1, wherein said compound is selected from the group consisting of:
- Dihydro-7-Mercapto-1-pyrindine6,6-bisphosphonic acid;
- Octahydro-7-Mercapto-1-pyrindine6,6-bisphosphonic acid;
- Dihydro-7-(2-mercaptoethyl)-1-pyrindine-6,6-bisphosphonic acid;
- Octahydro-7-(2-mercaptoethyl)-1-pyrindine-6,6-bisphosphonic acid;
- Dihydro-3-mercapto-1-pyrindine-6,6-bisphosphonic acid;
- Octahydro-3-mercapto-1-pyrindine-6,6-bisphosphonic acid;
- Dihydro-4-mercapto-2-pyrindine-6,6-bisphosphonic acid;
- Octahydro-4-mercapto-2-pyrindine-6,6-bisphosphonic acid;
- Dihydro-3-(4-mercaptobutyl)-1-pyrindine-6,6-bisphosphonic acid;
- Octahydro-3-(4-mercaptobutyl)-1-pyrindine-6,6-bisphosphonic acid;
- Dihydro-4-(4-mercaptobutyl)-2-pyrindine-6,6-bisphosphonic acid;
- Octahydro-4-(4-mercaptobutyl)-2-pyrindine-6,6-bisphosphonic acid;
- �1-hydroxy-(dihydro-7-mercapto-2-pyrind-7-yl) methylene!bis�phosphonic acid!;
- �Octahydro-4-(2-mercaptoethyl)-pyrrolo�3,2-b!pyridin-2-yl!bis�phosphonic acid!; and
- (3-acetylthio)-cyclopentane-1,1-bisphosphonic acid.
Parent Case Info
This is a CIP of Ser. No. 07/890,886 filed on May 29, 1992, now abandoned.
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Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
890886 |
May 1992 |
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