US 5,703,231 A · Process for making antimicrobial compounds

Abstract

The present invention provides a process for making a compound having a structure according to Formula (I) ##STR1## wherein A.sup.1, A.sup.2 and A.sup.3 are independently carbon or nitrogen and R.sup.1, R.sup.3, R.sup.4 and R.sup.6 are known quinolone substituents; and wherein one of R.sup.1, R.sup.3 or R.sup.6 may be a lactam-containing moiety; or a protected form, salt, pharmaceutically-acceptable salt, biohydrolyzable ester, or solvate thereof; the process comprising reacting one or more organosilicon compounds with a compound having a structure according to Formula (II) ##STR2## wherein A.sup.1, A.sup.2 and A.sup.3, R.sup.1, R.sup.3, R.sup.4 and R.sup.6 as described above; wherein one of R.sup.1, R.sup.3 or R.sup.6 may be a lactam-containing moiety; and X is a leaving group; or a protected form, salt, biohydrolyzable ester, or solvate thereof. The compounds prepared according to the processes of the invention are themselves useful as antimicrobials, or they may be used as intermediates for making other quinolone-containing antimicrobials.

A process for making a compound having a structure according to Formula (I) ##STR57## wherein (A)

(1) A.sup.1 is N or C(R.sup.7);
where
(a) R.sup.7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or --N(R.sup.8)(R.sup.9), and
(b) R.sup.8 and R.sup.9 are, independently, R.sup.8a ;
where R.sup.8a is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring;
or R.sup.8 and R.sup.9 together comprise a heterocyclic ring including the nitrogen to which they are bonded;
(2) A.sup.2 is N or C(R.sup.2);
where R.sup.2 is hydrogen or halogen;
(3) A.sup.3 is N or C(R.sup.5);
where R.sup.5 is hydrogen;
(4) R.sup.1 is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, heteroalkyl, --N(R.sup.8)(R.sup.9), or a lactam-containing moiety;
(5) R.sup.3 is hydrogen, halogen, alkyl, a carbocyclic ring, a heterocyclic ring, or a lactam-containing moiety;
(6) R.sup.4 is hydroxy;
and
(7) R.sup.6 is hydrogen, halogen, nitro, hydrazino, alkoxyamino, --N(R.sup.8)(R.sup.9), or a lactam-containing moiety;
except that if one of R.sup.1, R.sup.3, or R.sup.6 is a lactam-containing moiety, then the other two are not a lactam-containing moiety;
(B) and
(1) when A.sup.2 is C(R.sup.2), R.sup.2 and R.sup.3 may together comprise --O--(CH.sub.2)n--O--, where n is from 1 to 4;
(2) when A.sup.3 is C(R.sup.5), R.sup.4 and R.sup.5 may together comprise a heterocyclic ring including the carbon atom to which R.sup.4 and R.sup.5 are bonded and the carbon atoms of Formula (I) to which said carbon atom(s) are bonded;
and
(3) when A.sup.1 is C(R.sup.7), R.sup.3 and R.sup.7 may together comprise a heterocyclic ring including A.sup.1 and the carbon atom to which R.sup.3 is bonded;
or a protected form, salt, pharmaceutically-acceptable salt, biohydrolyzable ester, or solvate thereof;
the process comprising reacting one or more organosilicon compounds with a compound having a structure according to Formula (II), ##STR58## wherein (A)
(1) A.sup.1 is N or C(R.sup.7);
where
(a) R.sup.7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or --N(R.sup.8)(R.sup.9), and
(b) R.sup.8 and R.sup.9 are, independently, R.sup.8a ;
where R.sup.8a is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring;
or R.sup.8 and R.sup.9 together comprise a heterocyclic ring including the nitrogen to which they are bonded;
(2) A.sup.2 is N or C(R.sup.2);
where R.sup.2 is hydrogen or halogen;
(3) A.sup.3 is N or C(R.sup.5);
where R.sup.5 is hydrogen;
(4) R.sup.1 is hydrogen, alkyl, heteroalkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, --N(R.sup.8)(R.sup.9), or a lactam-containing moiety;
(5) R.sup.3 is hydrogen, halogen, alkyl, a carbocyclic ring, a heterocyclic ring, or a lactam-containing moiety;
(6) R.sup.4 is hydroxy;
(7) R.sup.6 is hydrogen, halogen, nitro, hydrazino, alkoxyamino, --N(R.sup.8)(R.sup.9), or a lactam-containing moiety;
and
(8) X is a leaving group;
except that if one of R.sup.1, R.sup.3, or R.sup.6 is a lactam-containing moiety, then the other two are not a lactam-containing moiety;
(B) and
(1) when A.sup.2 is C(R.sup.2), R.sup.2 and R.sup.3 may together comprise --O--(CH.sub.2)n--O--, where n is from 1 to 4;
(2) when A.sup.3 is C(R.sup.5), R.sup.4 and R.sup.5 may together comprise a heterocyclic ring including the carbon atoms to which R.sup.4 and R.sup.5 are bonded and the carbon atom of Formula (II) to which said carbon atom(s) are bonded;
and
(3) when A.sup.1 is C(R.sup.7), R.sup.3 and R.sup.7 may together comprise a heterocyclic ring including A1 and the carbon atom to which R.sup.3 is bonded;
or a protected form, salt, biohydrolyzable ester, or solvate thereof.

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Process for making antimicrobial compounds

Life of this patent

Process for making antimicrobial compounds

Life of this patent

Abstract

Claims25