New Coolants, and Preparations Containing Same

Physiological coolant of the general formula (Va)

• or the general formula (VIa)
• where in formulae (Va) and (VIa) in each case
• the radicals R1 and R2 may be identical or different and have the following meanings independently of one another:
• R1 H;
• or
• a group Q;
• or
• an optionally substituted linear or branched alkyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkynyl group;
• or
• an optionally substituted linear or branched alkoxy group;
• or
• an optionally substituted linear or branched alkylthio group;
• or
• an optionally substituted acyl group —R(C═O)—;
• or
• an optionally substituted cycloalkyl group;
• or
• an optionally substituted aryl group;
• or
• an optionally substituted heterocycloalkyl group;
• or
• is an optionally substituted heteroaryl group;
• R2 H;
• or
• a group Q;
• or
• an optionally substituted linear or branched alkyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkynyl group;
• or
• an optionally substituted linear or branched alkoxy group;
• or
• an optionally substituted linear or branched alkylthio group;
• or
• an optionally substituted acyl group R—(C═O)—;
• or
• an optionally substituted cycloalkyl group;
• or
• an optionally substituted aryl group;
• or
• an optionally substituted heterocycloalkyl group;
• or
• is an optionally substituted heteroaryl group;
• or R1 and R2 together with the C atoms to which they are bonded form a conjugated or non-conjugated ring system;
• Y is an optionally substituted branched alkyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkynyl group;
• or
• an optionally substituted linear or branched alkoxy group;
• or
• an optionally substituted acyl group R—(C═O)—;
• or
• an optionally substituted alkylaryl group;
• or
• is an optionally substituted alkylheteroaryl group;
• Z in the general formula (Va) NH2;
• or
• an NHRa group;
• or
• an NRaRb group;
• or
• an optionally substituted linear or branched alkyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkylthio group;
• or
• an optionally substituted linear or branched alkoxy group;
• or
• OH;
• or
• an optionally substituted cycloalkyl group;
• or
• an optionally substituted heterocycloalkyl group;
• or
• an optionally substituted aryl group;
• or
• is an optionally substituted heteroaryl group;
• or
• NH and together with the X forms a heterocyclic ring;
• Z in the general formula (VIa) NH2;
• or
• an NHRa group or an NRaRb group, with the exception of formula —NH-phenyl and —N(CH3)-phenyl;
• or
• an optionally substituted linear or branched alkyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkylthio group;
• or
• an optionally substituted linear or branched alkoxy group, with the exception of —OC2H5 and —OC(CH3)3;
• or
• an optionally substituted cycloalkyl group;
• or
• an optionally substituted heterocycloalkyl group;
• or
• an optionally substituted aryl group;
• or
• is an optionally substituted heteroaryl group;
• or
• NH and together with the X forms a heterocyclic ring;
• m is 1;
• whereby
• the group Q is a radical selected from the group consisting of:
• halogen, —OA, —SA, —NBB, —CF3, —CN, —OCN, —SCN, —NO, —NO2, —S(O)2a, —S(O)2OA, —OS(O)2a, —OS(O)2OA, —P(O)(OA)2, —P(O)(OA)(OA), —C(O)A, —C(S)A, —C(NA)A, —C(O)OA, —C(S)OA, —C(O)NBB, —C(NA)NBB, —OC(O)A, —OC(S)A, —OC(O)OA, —OC(S)OA, —NAC(O)A, —NAC(S)A, —NAC(O)OA, —NAC(S)OA, —NAC(O)NBB, —NAC(NA)A or —NAC(NA)NBB;
• whereby
• A is selected from the group consisting of:
• Hydrogen,
• optionally substituted linear or branched alkyl group, in particular optionally substituted C1- to C10-alkyl group, in particular optionally substituted C1- to C6-alkyl group, in particular optionally substituted C1-, C2-, C3- or C4-alkyl group,
• optionally substituted linear or branched alkoxy group, in particular optionally substituted C1-C6-alkoxy group, in particular optionally substituted C1-, C2-, C3- or C4-alkoxy group,
• optionally substituted linear or branched alkylthio group, in particular optionally substituted C1- to C6-alkylthio group, in particular optionally substituted C1-, C2-, C3- or C4-alkylthio group,
• optionally substituted cycloalkyl group,
• optionally substituted aryl group,
• optionally substituted heterocycloalkyl group,
• optionally substituted heteroaryl group;
• and/or
• B represents A or alternatively, two B's together with the nitrogen atom to which they are attached represent a four, five, six or seven membered heterocycloalkyl ring or heteroaryl ring, wherein the heterocycloalkyl ring or heteroaryl ring may comprise one, two, three or four identical or different heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• the optionally substituted linear or branched alkyl group is an optionally substituted C1- to C10-alkyl group, in particular an optionally substituted C1- to C6-alkyl group, is in particular an optionally substituted C1-, C2-, C3- or C4-alkyl group;
• the optionally substituted linear or branched alkenyl group is an optionally substituted C1- to C10-alkenyl group, in particular an optionally substituted C1- to C6-alkenyl group, is in particular an optionally substituted C1-, C2-, C3- or C4-alkenyl group;
• the optionally substituted linear or branched alkynyl group is an optionally substituted C1- to C10-alkynyl group, in particular an optionally substituted C1- to C6-alkynyl group, is in particular an optionally substituted C1-, C2-, C3- or C4-alkynyl group;
• the optionally substituted linear or branched alkoxy group is an optionally substituted C1- to C10-alkoxy group, in particular an optionally substituted C1- to C6-alkoxy group, is in particular an optionally substituted C1-, C2-, C3- or C4-alkoxy group;
• the optionally substituted linear or branched alkylthio group is an optionally substituted C1- to C10-alkylthio group, in particular an optionally substituted C1- to C6-alkylthio group,
• is in particular an optionally substituted C1-, C2-, C3- or C4-alkylthio group;
• in the acyl group R—(C═O)— the radical R represents hydrogen or an optionally substituted linear or branched C1- to C10-alkyl group, in particular an optionally substituted C1- to C6-alkyl group,
• is in particular an optionally substituted C1-, C2-, C3- or C4-acyl group;
• the optionally substituted cycloalkyl group is an optionally substituted three- to ten-membered, in particular three-, four-, five-, six- or seven-membered, monocyclic cycloalkyl group or an optionally substituted nine- to twelve-membered polycyclic, in particular bicyclic, cycloalkyl group;
• the optionally substituted aryl group is an optionally substituted three- to ten-membered, in particular three-, four-, five-, six- or seven-membered, monocyclic aryl group or an optionally substituted nine- to twelve-membered polycyclic, in particular bicyclic aryl group;
• the optionally substituted heterocycloalkyl group is an optionally substituted three- to ten-membered, in particular three-, four-, five-, six- or seven-membered monocyclic heterocycloalkyl group or an optionally substituted nine- to twelve-membered polycyclic, in particular bicyclic, heterocycloalkyl group, wherein the heterocycloalkyl group may comprise one, two, three or four identical or different heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• the optionally substituted heteroaryl group is an optionally substituted three- to ten-membered, in particular three-, four-, five-, six- or seven-membered monocyclic heteroaryl group or an optionally substituted nine- to twelve-membered polycyclic, in particular bicyclic, heteroaryl group, wherein the heteroaryl group may comprise one, two, three or four identical or different heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• Ra and/or Rb an optionally substituted linear or branched alkyl group, preferably a C1- to C3-alkyl group, preferably a methyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkynyl group;
• or
• an optionally substituted linear or branched alkoxy group;
• or
• an optionally substituted linear or branched alkylthio group;
• or
• an optionally substituted acyl group R—(C═O)—;
• or
• an optionally substituted cycloalkyl group;
• or
• an optionally substituted aryl group;
• or
• an optionally substituted heterocycloalkyl group;
• or
• is/are an optionally substituted heteroaryl group;
• or
• Ra and Rb, as defined above, are linked together and form a saturated or unsaturated ring;
• wherein the substituents are selected independently of one another;
• and their salts, in particular acid addition salts, with inorganic or organic acids, whereby the coolants may be present in stereoisomerically pure form or as mixtures of different stereoisomers;
• or the general formula (VIIa)
• or the general formula (VIIIa)
• where in each of the formulae (VIIa) and (VIIIa)
• the radicals R1 and R2 may be identical or different and have the following meanings independently of one another:
• R1 H;
• or
• a group Q;
• or
• an optionally substituted linear or branched alkyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkynyl group;
• or
• an optionally substituted linear or branched alkoxy group;
• or
• an optionally substituted linear or branched alkylthio group;
• or
• an optionally substituted acyl group —R(C═O)—;
• or
• an optionally substituted cycloalkyl group;
• or
• an optionally substituted aryl group;
• or
• an optionally substituted heterocycloalkyl group;
• or
• is an optionally substituted heteroaryl group;
• R2 H;
• or
• a group Q;
• or
• an optionally substituted linear or branched alkyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkynyl group;
• or
• an optionally substituted linear or branched alkoxy group;
• or
• an optionally substituted linear or branched alkylthio group;
• or
• an optionally substituted acyl group R—(C═O)—;
• or
• an optionally substituted cycloalkyl group;
• or
• an optionally substituted aryl group;
• or
• an optionally substituted heterocycloalkyl group;
• or
• is an optionally substituted heteroaryl group;
• or R1 and R2 together with the C atoms to which they are bonded form a conjugated or non-conjugated ring system;
• V S;
• or
• SO2;
• or
• an optionally substituted linear or branched alkyl group;
• or
• an optionally substituted cycloalkyl group;
• or
• is piperidinyl;
• Y is an optionally substituted branched alkyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkynyl group;
• or
• an optionally substituted linear or branched alkoxy group;
• or
• is an optionally substituted acyl group R—(C═O)—;
• Z NH2;
• or
• an NHRa group;
• or
• an NRaRb group;
• or
• an optionally substituted linear or branched alkyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkylthio group;
• or
• an optionally substituted linear or branched alkoxy group;
• or
• OH;
• or
• an optionally substituted cycloalkyl group;
• or
• an optionally substituted heterocycloalkyl group;
• or
• an optionally substituted aryl group;
• or
• is an optionally substituted heteroaryl group;
• or
• is NH and together with the X forms a heterocyclic ring;
• m is 1;
• whereby
• the group Q is a radical selected from the group consisting of:
• halogen, —OA, —SA, —NBB, —CF3, —CN, —OCN, —SCN, —NO, —NO2, —S(O)2A, —S(O)2OA, —OS(O)2A, —OS(O)2OA, —P(O)(OA)2, —P(O)(OA)(OA), —C(O)A, —C(S)A, —C(NA)A, —C(O)OA, —C(S)OA, —C(O)NBB, —C(NA)NBB, —OC(O)A, —OC(S)A, —OC(O)OA, —OC(S)OA, —NAC(O)A, —NAC(S)A, —NAC(O)OA, —NAC(S)OA, —NAC(O)NBB, —NAC(NA)A or —NAC(NA)NBB;
• whereby
• A is selected from the group consisting of:
• Hydrogen,
• optionally substituted linear or branched alkyl group, in particular optionally substituted C1- to C10-alkyl group, in particular optionally substituted C1- to C6-alkyl group, in particular optionally substituted C1-, C2-, C3- or C4-alkyl group,
• optionally substituted linear or branched alkoxy group, in particular optionally substituted C1-C6-alkoxy group, in particular optionally substituted C1-, C2-, C3- or C4-alkoxy group,
• optionally substituted linear or branched alkylthio group, in particular optionally substituted C1- to C6-alkylthio group, in particular optionally substituted C1-, C2-, C3- or C4-alkylthio group,
• optionally substituted cycloalkyl group,
• optionally substituted aryl group,
• optionally substituted heterocycloalkyl group,
• optionally substituted heteroaryl group;
• and/or
• B represents A or alternatively, two B's together with the nitrogen atom to which they are attached represent a four, five, six or seven membered heterocycloalkyl ring or heteroaryl ring, wherein the heterocycloalkyl ring or heteroaryl ring may comprise one, two, three or four identical or different heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• the optionally substituted linear or branched alkyl group is an optionally substituted C1- to C10-alkyl group, in particular an optionally substituted C1- to C6-alkyl group, is in particular an optionally substituted C1-, C2-, C3- or C4-alkyl group;
• the optionally substituted linear or branched alkenyl group is an optionally substituted C1- to C10-alkenyl group, in particular an optionally substituted C1- to C6-alkenyl group, is in particular an optionally substituted C1-, C2-, C3- or C4-alkenyl group;
• the optionally substituted linear or branched alkynyl group is an optionally substituted C1- to C10-alkynyl group, in particular an optionally substituted C1- to C6-alkynyl group, is in particular an optionally substituted C1-, C2-, C3- or C4-alkynyl group;
• the optionally substituted linear or branched alkoxy group is an optionally substituted C1- to C10-alkoxy group, in particular an optionally substituted C1- to C6-alkoxy group, is in particular an optionally substituted C1-, C2-, C3- or C4-alkoxy group;
• the optionally substituted linear or branched alkylthio group is an optionally substituted C1- to C10-alkylthio group, in particular an optionally substituted C1- to C6-alkylthio group,
• is in particular an optionally substituted C1-, C2-, C3- or C4-alkylthio group;
• in the acyl group R—(C═O)— the radical R represents hydrogen or an optionally substituted linear or branched C1- to C10-alkyl group, in particular an optionally substituted C1- to C6-alkyl group,
• is in particular an optionally substituted C1-, C2-, C3- or C4-acyl group;
• the optionally substituted cycloalkyl group is an optionally substituted three- to ten-membered, in particular three-, four-, five-, six- or seven-membered, monocyclic cycloalkyl group or an optionally substituted nine- to twelve-membered polycyclic, in particular bicyclic, cycloalkyl group;
• the optionally substituted aryl group is an optionally substituted three- to ten-membered, in particular three-, four-, five-, six- or seven-membered, monocyclic aryl group or an optionally substituted nine- to twelve-membered polycyclic, in particular bicyclic aryl group;
• the optionally substituted heterocycloalkyl group is an optionally substituted three- to ten-membered, in particular three-, four-, five-, six- or seven-membered monocyclic heterocycloalkyl group or an optionally substituted nine- to twelve-membered polycyclic, in particular bicyclic, heterocycloalkyl group, wherein the heterocycloalkyl group may comprise one, two, three or four identical or different heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• the optionally substituted heteroaryl group is an optionally substituted three- to ten-membered, in particular three-, four-, five-, six- or seven-membered monocyclic heteroaryl group or an optionally substituted nine- to twelve-membered polycyclic, in particular bicyclic, heteroaryl group, wherein the heteroaryl group may comprise one, two, three or four identical or different heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• Ra and/or Rb an optionally substituted linear or branched alkyl group;
• preferably a C1- to C3-alkyl group, preferably a methyl group;
• or
• an optionally substituted linear or branched alkenyl group;
• or
• an optionally substituted linear or branched alkynyl group;
• or
• an optionally substituted linear or branched alkoxy group;
• or
• an optionally substituted linear or branched alkylthio group;
• or
• an optionally substituted acyl group R—(C═O)—;
• or
• an optionally substituted cycloalkyl group;
• or
• an optionally substituted aryl group;
• or
• an optionally substituted heterocycloalkyl group;
• or
• is/are an optionally substituted heteroaryl group;
• or
• Ra and Rb, as defined above, are linked together and form a saturated or unsaturated ring;
• wherein the substituents are selected independently of one another;
• and their salts, in particular acid addition salts, with inorganic or organic acids, whereby the coolants may be present in stereoisomerically pure form or as mixtures of different stereoisomers.