Patent classifications
C07C321/16
Substituted bicyclic compounds
Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
Substituted bicyclic compounds
Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
SUBSTITUTED BICYCLIC COMPOUNDS
Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V):
##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
SUBSTITUTED BICYCLIC COMPOUNDS
Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V):
##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
THERAPEUTIC USE OF PLEUROMUTILINS
A compound of formula (I)
##STR00001## wherein n is 0 to 4; m is 0 or 1 with the proviso that the sulphur atom and R.sub.3 are in vicinal position (if m=0 then R.sub.3 is in position 2′, and if m=1 then R.sub.3 is on position 1′); R is ethyl or vinyl; R.sub.1 is hydrogen or (C.sub.1-6)alkyl, R.sub.2 is hydrogen or (C.sub.3-6)cycloalkyl, or unsubstituted (C.sub.1-6)alkyl, or (C.sub.1-6)alkyl substituted by one or more of hydroxy; preferably one or two, methoxy, halogen, (C.sub.3-6)cycloalkyl, or
R.sub.1 and R.sub.2 together with the nitrogen atom to which they are attached form a 5 to 7 membered heterocyclic ring containing at least 1 nitrogen atom or 1 nitrogen and 1 additional heteroatom e. g. selected from N or O, or R.sub.1 is hydroxy and R.sub.2 is formyl; R.sub.3 is OH, OR.sub.4, a halogen atom, or R.sub.3 is bound to 2′ and represents —O—(CH.sub.2).sub.p—O— with p is 2 or 3; R.sub.4 is unsubstituted (C.sub.1-6)alkyl or (C.sub.3-6)cycloalkyl, or a pharmaceutically acceptable salt, solvate, prodrug or metabolite thereof
for the specific use in the treatment or prevention of an inflammatory disease which is not mediated by bacteria.
THERAPEUTIC USE OF PLEUROMUTILINS
A compound of formula (I)
##STR00001## wherein n is 0 to 4; m is 0 or 1 with the proviso that the sulphur atom and R.sub.3 are in vicinal position (if m=0 then R.sub.3 is in position 2′, and if m=1 then R.sub.3 is on position 1′); R is ethyl or vinyl; R.sub.1 is hydrogen or (C.sub.1-6)alkyl, R.sub.2 is hydrogen or (C.sub.3-6)cycloalkyl, or unsubstituted (C.sub.1-6)alkyl, or (C.sub.1-6)alkyl substituted by one or more of hydroxy; preferably one or two, methoxy, halogen, (C.sub.3-6)cycloalkyl, or
R.sub.1 and R.sub.2 together with the nitrogen atom to which they are attached form a 5 to 7 membered heterocyclic ring containing at least 1 nitrogen atom or 1 nitrogen and 1 additional heteroatom e. g. selected from N or O, or R.sub.1 is hydroxy and R.sub.2 is formyl; R.sub.3 is OH, OR.sub.4, a halogen atom, or R.sub.3 is bound to 2′ and represents —O—(CH.sub.2).sub.p—O— with p is 2 or 3; R.sub.4 is unsubstituted (C.sub.1-6)alkyl or (C.sub.3-6)cycloalkyl, or a pharmaceutically acceptable salt, solvate, prodrug or metabolite thereof
for the specific use in the treatment or prevention of an inflammatory disease which is not mediated by bacteria.
Synthesis of cyclophanes from a self-assembly reaction
Disclosed herein is a novel method for preparing cyclophanes, comprising forming a disulfide cyclophane by contacting a linker moiety which includes two or more thiol groups, with a metal salt and an oxidant. The disulfide cyclophane is then desulfurized to form a thiacyclophane comprising thioether bridges. This thiacyclophane optionally may be further desulfurized to form an unsaturated hydrocarbon cyclophane, which can then be reduced to form a saturated hydrocarbon cyclophane. The various cyclophanes can be synthesized in a ring form, such as a dimer, trimer or tetramer etc., or they can be synthesized in a tetrahedral or larger structure. Also disclosed are novel cyclophanes formed by the disclosed method.
Synthesis of cyclophanes from a self-assembly reaction
Disclosed herein is a novel method for preparing cyclophanes, comprising forming a disulfide cyclophane by contacting a linker moiety which includes two or more thiol groups, with a metal salt and an oxidant. The disulfide cyclophane is then desulfurized to form a thiacyclophane comprising thioether bridges. This thiacyclophane optionally may be further desulfurized to form an unsaturated hydrocarbon cyclophane, which can then be reduced to form a saturated hydrocarbon cyclophane. The various cyclophanes can be synthesized in a ring form, such as a dimer, trimer or tetramer etc., or they can be synthesized in a tetrahedral or larger structure. Also disclosed are novel cyclophanes formed by the disclosed method.
Substituted bicyclic compounds
Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
Substituted bicyclic compounds
Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.