Compounds and compositions that can modulate mitochondrial function in neuronal cells are provided herein, as are methods for using the compounds and compositions to treat or prevent conditions such as Alzheimer's disease. For example, compounds of Formula I, compositions containing the compounds, and methods for using the compounds and compositions are provided herein:

##STR00001##

wherein X is absent, CH.sub.2, or C(O); R.sup.1 is H, OH, CN, NO.sub.2, halo, C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, C.sub.1-3 alkoxy, C.sub.1-3 haloalkoxy, C.sub.3-7 cycloalkyl, amino, C.sub.1-3 alkylamino, or di(C.sub.1-3 alkyl)amino; R.sup.2 is H or C.sub.1-6 alkyl; R.sup.3 is H, C.sub.1-6 alkyl, C(O)(C.sub.1-3 alkyl), or C(O)O(C.sub.1-3 alkyl); R.sup.4 is C.sub.3-10 cycloalkyl, C.sub.6-10 aryl, 5-10 membered heteroaryl, or 5-10 membered heterocycloalkyl, each optionally substituted by 1, 2, 3, or 4 independently selected R.sup.5 groups; and R.sup.5 is OH, CN, NO.sub.2, halo, C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, C.sub.1-3 alkoxy, C.sub.1-3 haloalkoxy, C.sub.3-7 cycloalkyl, amino, C.sub.1-3 alkylamino, or di(C.sub.1-3 alkyl)amino.

Compounds and compositions that can modulate mitochondrial function in neuronal cells are provided herein, as are methods for using the compounds and compositions to treat or prevent conditions such as Alzheimer's disease. For example, compounds of Formula I, compositions containing the compounds, and methods for using the compounds and compositions are provided herein:

##STR00001##

wherein X is absent, CH.sub.2, or C(O); R.sup.1 is H, OH, CN, NO.sub.2, halo, C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, C.sub.1-3 alkoxy, C.sub.1-3 haloalkoxy, C.sub.3-7 cycloalkyl, amino, C.sub.1-3 alkylamino, or di(C.sub.1-3 alkyl)amino; R.sup.2 is H or C.sub.1-6 alkyl; R.sup.3 is H, C.sub.1-6 alkyl, C(O)(C.sub.1-3 alkyl), or C(O)O(C.sub.1-3 alkyl); R.sup.4 is C.sub.3-10 cycloalkyl, C.sub.6-10 aryl, 5-10 membered heteroaryl, or 5-10 membered heterocycloalkyl, each optionally substituted by 1, 2, 3, or 4 independently selected R.sup.5 groups; and R.sup.5 is OH, CN, NO.sub.2, halo, C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, C.sub.1-3 alkoxy, C.sub.1-3 haloalkoxy, C.sub.3-7 cycloalkyl, amino, C.sub.1-3 alkylamino, or di(C.sub.1-3 alkyl)amino.

Compounds and compositions that can modulate mitochondrial function in neuronal cells are provided herein, as are methods for using the compounds and compositions to treat or prevent conditions such as Alzheimer's disease. For example, compounds of Formula I, compositions containing the compounds, and methods for using the compounds and compositions are provided herein: ##STR00001##
wherein X is absent, CH.sub.2, or C(O); R.sup.1 is H, OH, CN, NO.sub.2, halo, C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, C.sub.1-3 alkoxy, C.sub.1-3 haloalkoxy, C.sub.3-7 cycloalkyl, amino, C.sub.1-3 alkylamino, or di(C.sub.1-3 alkyl)amino; R.sup.2 is H or C.sub.1-6 alkyl; R.sup.3 is H, C.sub.1-6 alkyl, C(O)(C.sub.1-3 alkyl), or C(O)O(C.sub.1-3 alkyl); R.sup.4 is C.sub.3-10 cycloalkyl, C.sub.6-10 aryl, 5-10 membered heteroaryl, or 5-10 membered heterocycloalkyl, each optionally substituted by 1, 2, 3, or 4 independently selected R.sup.5 groups; and R.sup.5 is OH, CN, NO.sub.2, halo, C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, C.sub.1-3 alkoxy, C.sub.1-3 haloalkoxy, C.sub.3-7 cycloalkyl, amino, C.sub.1-3 alkylamino, or di(C.sub.1-3 alkyl)amino.

Compounds and compositions that can modulate mitochondrial function in neuronal cells are provided herein, as are methods for using the compounds and compositions to treat or prevent conditions such as Alzheimer's disease. For example, compounds of Formula I, compositions containing the compounds, and methods for using the compounds and compositions are provided herein: ##STR00001##
wherein X is absent, CH.sub.2, or C(O); R.sup.1 is H, OH, CN, NO.sub.2, halo, C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, C.sub.1-3 alkoxy, C.sub.1-3 haloalkoxy, C.sub.3-7 cycloalkyl, amino, C.sub.1-3 alkylamino, or di(C.sub.1-3 alkyl)amino; R.sup.2 is H or C.sub.1-6 alkyl; R.sup.3 is H, C.sub.1-6 alkyl, C(O)(C.sub.1-3 alkyl), or C(O)O(C.sub.1-3 alkyl); R.sup.4 is C.sub.3-10 cycloalkyl, C.sub.6-10 aryl, 5-10 membered heteroaryl, or 5-10 membered heterocycloalkyl, each optionally substituted by 1, 2, 3, or 4 independently selected R.sup.5 groups; and R.sup.5 is OH, CN, NO.sub.2, halo, C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, C.sub.1-3 alkoxy, C.sub.1-3 haloalkoxy, C.sub.3-7 cycloalkyl, amino, C.sub.1-3 alkylamino, or di(C.sub.1-3 alkyl)amino.

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.

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.

Disclosed herein are compounds of Formulae (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is) and (It), methods of synthesizing compounds of Formulae (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is) and (It), and methods of using compounds of Formulae (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is) and (It) as an analgesic.

Disclosed herein are compounds of Formulae (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is) and (It), methods of synthesizing compounds of Formulae (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is) and (It), and methods of using compounds of Formulae (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is) and (It) as an analgesic.

The present invention provides processes and synthetic intermediate (Ia) for the synthesis of 4-substituted ((1S, 2S, 4R)-2-hydroxy-4-{7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl sulfamates. These sulfamate compounds are E1 activating enzyme inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with E1 activity. ##STR00001##

The present invention provides processes and synthetic intermediate (Ia) for the synthesis of 4-substituted ((1S, 2S, 4R)-2-hydroxy-4-{7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl sulfamates. These sulfamate compounds are E1 activating enzyme inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with E1 activity. ##STR00001##