Tricyclic benzodiazepines as vasopressin receptor antagonists

A compound of the formula (IV):

• wherein
• X is selected from the group consisting of CH2, S and O;
• R1 is one to two substituents independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, amino C1-C4 alkyl and nitro;
• R5 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, chlorine, fluorine, hydroxy, dialkylamino (wherein the alkyl groups on the amino may be the same or different), trifluoromethyl and trifluoromethoxy;
• R6 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, phenyl (wherein the phenyl is optionally substituted with from one to two substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, halogen, cyano, hydroxy, amino, nitro, C1-C4 alkylamino, C1-C4 dialkylamino (wherein the alkyl groups on the amino may be the same or different), C1-C4 alkylsulfonyl, C1-C4 alkylthio, or C1-C4 alkylsulfinyl);
• aralkyl (wherein the alkyl or aryl portions are optionally independently substituted and the alkyl portion may be substituted with at least one fluorine and/or the aryl portion may be independently substituted with from one to two substituents selected from halogen, C1-C4 alkyl, C1-C6 alkylthio or hydroxyl), aralkoxy (wherein the alkoxy or aryl portions are optionally independently substituted and the alkoxy portion may be substituted with at least one fluorine and/or the aryl portion may be independently substituted with from one to two substituents selected from halogen, C1-C4 alkyl, C1-C6 alkylthio and hydroxyl), heteroaryl (optionally substituted with one to two substituents independently selected from C1-C4 alkyl or halogen), heteroaryl(C1-C8)alkyl (wherein the heteroaryl portion is optionally substituted with one to two substituents selected from C1-C8 alkyl), (halo)1-3(C1-C4)alkylthio and halogen;
• and
• R7 is independently selected from the group consisting of hydrogen, fluorine, chlorine, iodine, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl and combinations thereof, wherein R7 represent one to four independently selected groups;
• and pharmaceutically acceptable salts thereof.

The compound of formula (IVa):

• wherein
• Y is selected from the group consisting of CH2 and CH as part of an olefin;
• X is selected from the group consisting of CH2, CH as part of an olefin, S and O;
• with the proviso that if Y is CH as part of an olefin, then X is CH as part of an olefin;
• R5 is one to two substituents independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, chlorine, fluorine, hydroxy, dialkylamino (wherein the alkyl groups may be the same or different), trifluoromethyl and trifluoromethoxy;
• and pharmaceutically acceptable salts thereof.

A compound of formula (I):

• wherein
• A is selected from the group consisting of —C(O)—, SO2 and CH2;
• Y is selected from the group consisting of CH2 and CH as part of an olefin;
• X is selected from the group consisting of CH2, CH as part of an olefin, NR3, S, O and SO2;
• with the proviso that if Y is CH as part of an olefin, then X is CH as part of an olefin;
• Z is selected from the group consisting of N and CH;
• R1 is one to two substituents independently selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, aminoalkyl, and nitro;
• R2 is selected from the group consisting of NR4COAr, NR4CO-heteroaryl, NR4Ar, CH═CH—Ar, CF═CH—Ar, CH═CF—Ar, CCl═CH—Ar, CH═CCl—Ar, CH═CH-heteroaryl, CF═CH-heteroaryl, CH═CF-heteroaryl, —CCl═CH-heteroaryl, CH═CCl-heteroaryl, OCH2—Ar, OCH2-heteroaryl, SCH2—Ar and NR4CH2Ar;
• R3 is selected from the group consisting of hydrogen, acyl, alkyl, aralkyl, alkoxycarbonyl, alkylsulfonyl, fluorinated alkyl and arylsulfonyl;
• Ar is selected from the group consisting of naphthyl, wherein naphthyl is optionally substituted with from one to four substituents independently selected from the group consisting of C1-C8 alkyl, C1-C8 alkoxy, fluorinated C1-C8 alkyl, fluorinated C1-C8 alkoxy, halogen, cyano, hydroxy, amino, nitro, C1-C4 alkylamino and C1-C4 dialkylamino (wherein the alkyl groups on the amino may be the same or different);
• and phenyl, wherein phenyl is optionally substituted with from one to four substituents independently selected from C1-C8 alkyl, C1-C8 alkoxy, fluorinated C1-C8 alkyl, fluorinated C1-C8 alkoxy, C1-C8 aralkyl (wherein the alkyl portion is optionally substituted with at least one fluorine and the aryl portion is optionally substituted with from one to two substituents selected from the group consisting of halogen, C1-C4 alkyl, C1-C6 alkylthio and hydroxy), C1-C8 aralkoxy (wherein the alkoxy portion is optionally substituted with at least one fluorine and the aryl portion is optionally substituted with from one to two substituents selected from the group consisting of halogen, C1-C4 alkyl, C1-C6 alkylthio and hydroxy), halogen, cyano, hydroxy, amino, nitro, C1-C8 alkylamino, C1-C4 dialkylamino (wherein the alkyl groups on the amino may be the same or different), C1-C8 alkylsulfonyl, C1-C8 alkylthio, (halo)1-3(C1-C8)alkylthio, C1-C8 alkylsulfinyl, heteroaryl (optionally substituted with one to two substituents independently selected from the group consisting of C1-C8 alkyl and halogen), heteroaryl(C1-C8)alkyl (wherein the heteroaryl portion is optionally substituted with one to two substituents independently selected from C1-C8 alkyl) and phenyl (optionally substituted with from one to two substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, halogen, cyano, hydroxy, amino, nitro, C1-C4 alkylamino, C1-C4 dialkylamino (wherein the alkyl groups on the amino may be the same or different), C1-C4 alkylsulfonyl, C1-C4 alkylthio and C1-C4 alkylsulfinyl);
• R4 is selected from the group consisting of hydrogen and C1-C4 alkyl;
• R5 is one to two substituents independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, chlorine, fluorine, hydroxy, dialkylamino (wherein the alkyl groups on the amino may be the same or different), trifluoromethyl and trifluoromethoxy;
• and pharmaceutically acceptable salts thereof.