Nitrate esters and their use for neurological conditions

A pharmaceutical composition comprising an effective amount of an aliphatic nitrate ester or a pharmaceutically acceptable salt thereof, having the formula:

• ##STR8## where X is CN, NHOH, N.sub.2 H.sub.3, N.sub.2 H.sub.2 R.sub.13, N.sub.2 HR.sub.13 R.sub.14, N.sub.3, SCN, SCN.sub.2 H.sub.2 (R.sub.5).sub.2, SCN.sub.2 H.sub.3 (R.sub.5), SC(O)N(R.sub.5).sub.2, SC(O)NHR.sub.5, CO.sub.2 M, CO.sub.2 H, CO.sub.2 R.sub.11, C(O), C(O)R.sub.12, C(O)(OR.sub.13), PO.sub.2 M, P(O)(OR.sub.14), P(O)(R.sub.13), SO, SO.sub.2, C(O)(SR.sub.13), or SSR.sub.4 ;
• Y is SCN, SCN.sub.2 H.sub.2 (R.sub.5).sub.2, SC(O)NHR.sub.5, SC(O)N(R.sub.5).sub.2, SR.sub.4, SR.sub.10, SSR.sub.10, SO.sub.2 M, SO.sub.3 M, PO.sub.3 HM, PO.sub.3 M.sub.2, P(O)(OR.sub.5)(OR.sub.6), or P(O)(OR.sub.6)(OM), CN, N.sub.3, N.sub.2 H.sub.2 R.sub.13, N.sub.2 HR.sub.13 R.sub.14, CO.sub.2 M, CO.sub.2 H, CO.sub.2 R.sub.11, C(O)R.sub.12, C(O)(SR.sub.13), or does not exist;
• R.sub.5, R.sub.6, R.sub.8, R.sub.9, R.sub.10,R.sub.12, R.sub.13, R.sub.14, R.sub.15, R.sub.16, are the same or different alkyls containing 1-12 carbon atoms which may contain 1-4 ONO.sub.2 substituents or C.sub.1 or C.sub.2 connections to R.sub.1 -R.sub.3, in cyclic derivatives;
• R.sub.7, R.sub.11 are C.sub.1 -C.sub.8, alkyl or acyl,
• R.sub.2 and R.sub.4 are the same or different and selected from H, ONO.sub.2, C.sub.1 -C.sub.4 alkyl optionally bearing 1-3 nitrate groups, and acyl groups (--C(O)R.sub.10);
• R.sub.1 and R.sub.3 are the same or different and selected from H, C.sub.1 -C.sub.4 alkyl and chains, which may include one O, linking R.sub.1 and R.sub.3 to form pentosyl, hexosyl, cyclopentyl or cycohexyl rings, which rings optionally bear hydroxyl substituents;
• and
• M is H, Na.sup.+, K.sup.+, NH.sub.4.sup.+ or N.sup.+ H.sub.n R.sub.11(4-n) where n is 0-3;
• and with the proviso that, when R.sub.6 is an alkyl group, and R, R.sub.2 and R.sub.4 are H, R.sub.3 is not H or methyl;
• in admixture with a pharmaceutically acceptable carrier therefor.

An aliphatic nitrate ester or salt thereof, containing at least one nitrate group, in which a S or P atom is situated .beta. or .gamma. to a nitrate group, or their congener, having a general formula:

• ##STR10## where X is CH.sub.2, O, NH, S or NCH.sub.3 ;
• Y is SCN, SCN.sub.2 H.sub.2 (R.sub.5).sub.2, SC(O)NHR.sub.5, SC(O)N(R.sub.5).sub.2, CN, N.sub.3, N.sub.2 H.sub.2 R.sub.13, N.sub.2 HR.sub.13 R.sub.14, CO.sub.2 M, CO.sub.2 H, CO.sub.2 R.sub.11, C(O)R.sub.12, C(O)(SR.sub.13);
• R.sub.5, R.sub.6, R.sub.8, R.sub.9, R.sub.10, R.sub.12, R.sub.13, R.sub.14, R.sub.15, R.sub.16, are the same or different alkyls containing 1-12 carbon atoms which may contain 1-4 ONO.sub.2 substituents or C.sub.1 or C.sub.2 connections to R.sub.1 -R.sub.3 in cyclic derivatives;
• R.sub.7, R.sub.11 are C.sub.1 -C.sub.8, alkyl or acyl;
• R.sub.2 and R.sub.4 are the same or different and selected from H, ONO.sub.2, C.sub.1 -C.sub.4 alkyl optionally bearing 1-3 nitrate groups, and acyl groups (--C(O)R.sub.10);
• R.sub.1 and R.sub.3 are the same or different and selected from H, C.sub.1 -C.sub.4 alkyl and chains, which may include one O, linking R.sub.1 and R.sub.3 to form pentosyl, hexosyl, cyclopentyl or cycohexyl rings, which rings optionally bear hydroxyl substituents;
• and
• M is H, Na.sup.+, K.sup.+, NH.sub.4.sup.+ or N.sup.+ H.sub.n R.sub.11(4-n) where n is 0-3;
• and with the proviso that, when X is O, Y is not C(O)R.sub.l2,
• and with the proviso that, when R.sub.5 is an alkyl group, and R, R.sub.2 and R.sub.4 are H, R.sub.3 is not H or methyl.

An aliphatic nitrate ester or salt thereof, containing at least one nitrate group, in which a S or P atom is situated .beta. or .gamma. to a nitrate group, or their congener, having a general formula:

• ##STR11## where X is SCN, CH.sub.2, SCN.sub.2 H.sub.3 (R.sub.5), C(O), C(O)R.sub.12, C(O)(OR.sub.13), C(O)(SR.sub.13), or NCH.sub.3 ;
• Y is SCN, SCN.sub.2 H.sub.2 (R.sub.5).sub.2, CO.sub.2 R.sub.11, C(O)R.sub.12, C(O)(SR.sub.13), or does not exist;
• R.sub.5, R.sub.6, R.sub.8, R.sub.9, R.sub.10, R.sub.12, R.sub.13, R.sub.14,R.sub.15, R.sub.16, are the same or different alkyls containing 1-12 carbon atoms which may contain 1-4 ONO.sub.2 substituents or C.sub.1 or C.sub.2 connections to R.sub.1 -R.sub.3 in cyclic derivatives;
• R.sub.7, R.sub.11 are C.sub.1 -C.sub.8, alkyl or acyl;
• R.sub.2 and R.sub.4 are the same or different and selected from H, ONO.sub.2, C.sub.1 -C.sub.4 alkyl optionally bearing 1-3 nitrate groups, and acyl groups (--C(O)R.sub.10);
• R.sub.1 and R.sub.3 are the same or different and selected from H, C.sub.1 -C.sub.4 alkyl and chains, which may include one O, linking R.sub.1 and R.sub.3 to form pentosyl, hexosyl, cyclopentyl or cycohexyl rings, which rings optionally bear hydroxyl substituents;
• and
• M is H, Na.sup.+, K.sup.+, NH.sub.4.sup.+ or N.sup.+ H.sub.n R.sub.11(4-n) where n is 0-3;
• and with the proviso that, when R.sub.6 is an alkyl group, and R.sub.1 R.sub.2 and R.sub.4 are H, R.sub.3 is not H or methyl.