Claims for Patent: 10,717,721

Summary for Patent: 10,717,721

Title:	Substituted piperaziniums for the treatment of emesis
Abstract:	Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK.sub.1) receptor. The compounds have the general formula (I): ##STR00001##
Inventor(s):	Fadini; Luca (Giubiasco, CH), Manini; Peter (Giubiasco, CH), Pietra; Claudio (Como, IT), Giuliano; Claudio (Como, IT), Lovati; Emanuela (Mendrisio, CH), Cannella; Roberta (Varese, IT), Venturini; Alessio (Varese, IT), Stella; Valentino J. (Lawrence, KS)
Assignee:	Helsinn Healthcare SA (Lugano/Pazzallo, CH)
Application Number:	16/228,835
Patent Claims:	1. A compound of formula (VI): ##STR00051## or a pharmaceutically acceptable salt thereof, wherein: each R.sub.1 is independently hydrogen, halogen, alkyl, alkylNR.sup.101R.sup.102, alkenyl,--C(O)R.sup.101, --C(O)NR.sup.101R.sup.102, --C(O)OR.sup.101, --NR.sup.101R.sup.102, --NR.sup.101C(O)R.sup.102, --OR.sup.101, --SR.sup.101, --S(O).sub.2R.sup.102, --S(O).sub.2NR.sup.101R.sup.102, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each optionally substituted with one or more independently selected R.sup.103 substituents; each R.sub.2 is independently hydrogen, halogen, alkyl, alkylNR.sup.101R.sup.102, alkenyl,--C(O)R.sup.101, --C(O)NR.sup.101R.sup.102, --C(O)OR.sup.101, --NR.sup.101R.sup.102, --NR.sup.101C(O)R.sup.102, --OR.sup.101, --SR.sup.101, --S(O).sub.2R.sup.102, --S(O).sub.2NR.sup.101R.sup.102, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each optionally substituted with one or more independently selected R.sup.103 substituents; R.sub.5 is hydrogen, halogen, alkyl, alkylNR.sup.101R.sup.102, alkenyl,--C(O)R.sup.101, --C(O)NR.sup.101R.sup.102, --C(O)OR.sup.101, --NR.sup.101R.sup.102, --NR.sup.101C(O)R.sup.102, --OR.sup.101, --SR.sup.101, --S(O).sub.2R.sup.102, --S(O).sub.2NR.sup.101R.sup.102, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each optionally substituted with one or more independently selected R.sup.103 substituents; R.sub.6 is hydrogen, halogen, alkyl, alkylNR.sup.101R.sup.102, alkenyl,--C(O)R.sup.101, --C(O)NR.sup.101R.sup.102, --C(O)OR.sup.101, --NR.sup.101R.sup.102, --NR.sup.101C(O)R.sup.102, --OR.sup.101, --SR.sup.101, --S(O).sub.2R.sup.102, --S(O).sub.2NR.sup.101R.sup.102, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each optionally substituted with one or more independently selected R.sup.103 substituents; each R.sub.7 is independently hydrogen, halogen, alkyl, alkenyl, amino, --OR.sup.104, or cycloalkyl, wherein the alkyl, alkenyl, amino and cycloalkyl are each optionally substituted with one or more independently selected R.sup.103 substituents; R.sub.200 is hydrogen, alkyl, or cycloalkyl, wherein the alkyl and cycloalkyl are each optionally substituted with one or more independently selected R.sup.103 substituents; R.sub.300 is hydrogen, alkyl, or cycloalkyl, wherein the alkyl and cycloalkyl are each optionally substituted with one or more independently selected R.sup.103 substituents; R.sup.101 is hydrogen, halogen, cyano, nitro, oxide, alkyl, alkenyl, --C(O)OR.sup.104, --C(O)NR.sup.104R.sup.105, --C(O)OR.sup.104, --NR.sup.104R.sup.105, --NR.sup.104C(O)R.sup.105, --NR.sup.104 S(O).sub.2R.sup.105, --OR.sup.104, --SR.sup.104, --S(O).sub.2NR.sup.104R.sup.105, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each optionally substituted with one or more independently selected R.sup.103 substituents; R.sup.102 is hydrogen, halogen, cyano, nitro, oxide, alkyl, alkenyl, --C(O)OR.sup.104, --C(O)NR.sup.104R.sup.105, --C(O)OR.sup.104, --NR.sup.104R.sup.105, --NR.sup.104C(O)R.sup.105, --NR.sup.104 S(O).sub.2R.sup.105, --OR.sup.104, --SR.sup.104, --S(O).sub.2NR.sup.104R.sup.105, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each optionally substituted with one or more independently selected R.sup.103 substituents; or R.sup.101and R.sup.102, together with the atoms to which they are attached, form a fused or non-fused monocyclic, bicyclic or tricyclic carbocyclic or heterocyclic ring, which is optionally and independently substituted with one or more independently selected R.sup.103 substituents; each R.sup.103 is independently halogen, cyano, nitro, oxide, alkyl, alkenyl, --C(O)OR.sup.104, --C(O)NR.sup.104R.sup.105, --C(O)OR.sup.104, --NR.sup.104R.sup.105, --NR.sup.104C(O)R.sup.105, --NR.sup.104 S(O).sub.2R.sup.105, --OR.sup.104, --SR.sup.104, --S(O).sub.2NR.sup.104R.sup.105, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R.sup.104 is hydrogen, halogen, cyano, nitro, oxide, alkyl, hydroxyalkyl, alkoxyalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, alkenyl, amino, hydroxy, alkoxy, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R.sup.105 is hydrogen, halogen, cyano, nitro, oxide, alkyl, hydroxyalkyl, alkoxyalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, alkenyl, amino, hydroxy, alkoxy, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is 0, 1, 2, 3, or 4; each p is independently 0 or 1; and s is 0, 1, 2, 3, or 4; with a proviso that if a non-pyridine N-Oxide is present on the compound of formula (VI), then the total number of N-Oxides on the compound of formula (VI) is greater than one. 2. A compound selected from the group consisting of: ##STR00052## ##STR00053## or a pharmaceutically acceptable salt thereof.