This application discloses a novel process to synthesize 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one compounds, which may be used, for example, as NK-1 inhibitor compounds in pharmaceutical preparations, intermediates useful in said process, and processes for preparing said intermediates; also disclosed is a process for removal of metals from N-heterocyclic carbine metal complexes.

This application discloses a novel process to synthesize 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one compounds, which may be used, for example, as NK-1 inhibitor compounds in pharmaceutical preparations, intermediates useful in said process, and processes for preparing said intermediates; also disclosed is a process for removal of metals from N-heterocyclic carbine metal complexes.

The N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is 1 or 2; L represents a C.sub.1-3alkyl linker optionally substituted with one or two substituents selected from C.sub.1-4alkyl, C.sub.1-3alkyloxy-C.sub.1-4alkyl-, hydroxy-C.sub.1-4alkyl, hydroxy, C.sub.1-3alkyloxy- or phenyl-C.sub.1-4alkyl; M represents a direct bond or a C.sub.1-3alkyl linker optionally substituted with one or two substituents selected from hydroxy, C.sub.1-4alkyl or C.sub.1-4alkyloxy; R.sup.1 and R.sup.2 each independently represent hydrogen, halo, cyano, hydroxy, C.sub.1-4alkyl optionally substituted with halo, C.sub.1-4alkyloxy- optionally substituted with one or where possible two or three substituents selected from hydroxy, Ar.sup.1 and halo; or R.sup.1 and R.sup.2 taken together with the phenyl ring to which they are attached form naphtyl or 1,3-benzodioxolyl, wherein said naphtyl or 1,3-benzodioxolyl are optionally substituted with halo; R.sup.3 represents hydrogen, halo, C.sub.1-4alkyl, C.sub.1-4alkyloxy-, cyano or hydroxy; R.sup.4 represents hydrogen, halo, C.sub.1-4alkyl, C.sub.1-4alkyloxy-, cyano or hydroxy; R.sup.5 represents hydrogen, C.sub.1-4alkyl or Ar.sup.2—C.sub.1-4alkyl-; R.sup.6 represents hydrogen, halo, C.sub.1-4alkyl or C.sub.1-4alkyoxy-; Ar.sup.1 and Ar.sup.2 each independently represent phenyl or naphtyl wherein said phenyl and naphtyl are optionally substituted with C.sub.1-4alkyl, C.sub.1-4alkyloxy-, or phenyl-C.sub.1-4alkyl;
for use as a medicine. ##STR00001##

The N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is 1 or 2; L represents a C.sub.1-3alkyl linker optionally substituted with one or two substituents selected from C.sub.1-4alkyl, C.sub.1-3alkyloxy-C.sub.1-4alkyl-, hydroxy-C.sub.1-4alkyl, hydroxy, C.sub.1-3alkyloxy- or phenyl-C.sub.1-4alkyl; M represents a direct bond or a C.sub.1-3alkyl linker optionally substituted with one or two substituents selected from hydroxy, C.sub.1-4alkyl or C.sub.1-4alkyloxy; R.sup.1 and R.sup.2 each independently represent hydrogen, halo, cyano, hydroxy, C.sub.1-4alkyl optionally substituted with halo, C.sub.1-4alkyloxy- optionally substituted with one or where possible two or three substituents selected from hydroxy, Ar.sup.1 and halo; or R.sup.1 and R.sup.2 taken together with the phenyl ring to which they are attached form naphtyl or 1,3-benzodioxolyl, wherein said naphtyl or 1,3-benzodioxolyl are optionally substituted with halo; R.sup.3 represents hydrogen, halo, C.sub.1-4alkyl, C.sub.1-4alkyloxy-, cyano or hydroxy; R.sup.4 represents hydrogen, halo, C.sub.1-4alkyl, C.sub.1-4alkyloxy-, cyano or hydroxy; R.sup.5 represents hydrogen, C.sub.1-4alkyl or Ar.sup.2—C.sub.1-4alkyl-; R.sup.6 represents hydrogen, halo, C.sub.1-4alkyl or C.sub.1-4alkyoxy-; Ar.sup.1 and Ar.sup.2 each independently represent phenyl or naphtyl wherein said phenyl and naphtyl are optionally substituted with C.sub.1-4alkyl, C.sub.1-4alkyloxy-, or phenyl-C.sub.1-4alkyl;
for use as a medicine. ##STR00001##

Disclosed herein are compositions and methods of treating osteroporosis, bone fracture, bone loss, and increasing bone density by administration of compounds of formula (I)

##STR00001##

or compositions comprising a compound of formula (I) and a pharmaceutically acceptable carrier, wherein L.sup.1, L.sup.2, L.sup.4, R.sup.1, R.sup.4, R.sup.5, R.sup.6, and s are as defined in the specification.

Disclosed herein are compositions and methods of treating osteroporosis, bone fracture, bone loss, and increasing bone density by administration of compounds of formula (I)

##STR00001##

or compositions comprising a compound of formula (I) and a pharmaceutically acceptable carrier, wherein L.sup.1, L.sup.2, L.sup.4, R.sup.1, R.sup.4, R.sup.5, R.sup.6, and s are as defined in the specification.

Compounds, compositions and methods for preventing, treating or curing a coronavirus, picornavirus, and/or hepeviridae virus infection in human subjects or other animal hosts. Specific viruses that can be treated include enteroviruses. In one embodiment, the compounds can be used to treat an infection with a severe acute respiratory syndrome virus, such as human coronavirus 229E, SARS, MERS, SARS-CoV-1 (OC43), and SARS-CoV-2. In another embodiment, the methods are used to treat a patient co-infected with two or more of these viruses, or a combination of one or more of these viruses and norovirus.

The present specification provides a heterocyclic compound represented by Chemical Formula 1, an organic light emitting device comprising the same, a composition for an organic material layer of an organic light emitting device, and a method for manufacturing an organic light emitting device.

A cyclic compound represented by Chemical Formula 1 and an organic light emitting device using the same, the compound used as a material of an organic material layer of the organic light emitting device and providing improved properties of efficiency, driving voltage, and lifetime characteristics of the organic light emitting device.

##STR00001##

Compounds and treatment methods with compounds exhibiting antiviral activity and/or inhibition of viral replication against viruses, particularly those belonging to the picornavirus-like supercluster, including coronavirus having a formula:

##STR00001##

or a prodrug or pharmaceutically-acceptable salt thereof, where: each X comprises at least one cyclic moiety directly attached to the oxygen or connected via an alkyl linkage, where at least one of the linkage and/or the X moiety comprises a deuterium substitution; and Z is selected from the group consisting of aldehydes and bisulfite salts, or the ester or carbamate prodrugs thereof.