Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

The object of the present invention is to provide 1-(1-tert-butoxycarbonyl piperidylacetyl)-4-mesyloxypiperidine having a low content of impurities

The object can be solved by a method for preparing 1-(1-benzyl piperidylacetyl)-4-hydroxypiperidine, comprising the steps of: (1) reductively reacting 1-benzyl-4-piperidylidene acetic acid ethyl ester represented by the formula [1]:

##STR00001##

to obtain 1-benzyl-4-piperidyl acetic acid ethyl ester represented by the formula [2]:

##STR00002##

(2) adding an ammonium chloride aqueous solution and an organic solvent to the liquid containing 1-benzyl-4-piperidyl acetic acid ethyl ester, mixing the whole, and separating into an organic layer and an aqueous layer, (3) collecting 1-benzyl-4-piperidyl acetic acid ethyl ester from the organic layer, and (4) reacting the obtained 1-benzyl-4-piperidyl acetic acid ethyl ester with 4-hydroxypiperidine represented by the formula [3]:

##STR00003##

in the presence of base, to obtain 1-(1-benzyl-4-piperidylacetyl)-4-hydroxypiperidine represented by the formula [4]:

##STR00004##

The object of the present invention is to provide 1-(1-tert-butoxycarbonyl piperidylacetyl)-4-mesyloxypiperidine having a low content of impurities

The object can be solved by a method for preparing 1-(1-benzyl piperidylacetyl)-4-hydroxypiperidine, comprising the steps of: (1) reductively reacting 1-benzyl-4-piperidylidene acetic acid ethyl ester represented by the formula [1]:

##STR00001##

to obtain 1-benzyl-4-piperidyl acetic acid ethyl ester represented by the formula [2]:

##STR00002##

(2) adding an ammonium chloride aqueous solution and an organic solvent to the liquid containing 1-benzyl-4-piperidyl acetic acid ethyl ester, mixing the whole, and separating into an organic layer and an aqueous layer, (3) collecting 1-benzyl-4-piperidyl acetic acid ethyl ester from the organic layer, and (4) reacting the obtained 1-benzyl-4-piperidyl acetic acid ethyl ester with 4-hydroxypiperidine represented by the formula [3]:

##STR00003##

in the presence of base, to obtain 1-(1-benzyl-4-piperidylacetyl)-4-hydroxypiperidine represented by the formula [4]:

##STR00004##

The invention provides substituted, saturated and unsaturated N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

The invention provides substituted, saturated and unsaturated N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

Disclosed are compounds of formulas (I)-(IX) for treating or preventing a disease or disorder responsive to antagonism of a P2Y.sub.14R receptor agonist in a mammal in need thereof, wherein R.sup.1-R.sup.8, X, Y, Z, X′, Y′, Z′, and A are as defined herein, that are useful in treating an inflammatory such as asthma, cystic fibrosis, and sterile inflammation of the kidney. ##STR00001##

Disclosed are compounds of formulas (I)-(IX) for treating or preventing a disease or disorder responsive to antagonism of a P2Y.sub.14R receptor agonist in a mammal in need thereof, wherein R.sup.1-R.sup.8, X, Y, Z, X′, Y′, Z′, and A are as defined herein, that are useful in treating an inflammatory such as asthma, cystic fibrosis, and sterile inflammation of the kidney. ##STR00001##

The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity.

The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity.

The invention provides amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.