Compounds comprising piperazines, piperidines, spiro-furanopiperidines, and analogs thereof are provided that are modulators, such as positive allosteric modulators, of one or more subclasses of vasopressin receptors. The compounds can be selective modulators of one or more subclasses of vasopressin receptors. Compounds of the invention can be used in the treatment of a condition wherein modulating a vasopressin receptor is medically indicated for treatment of the condition.

Compounds comprising piperazines, piperidines, spiro-furanopiperidines, and analogs thereof are provided that are modulators, such as positive allosteric modulators, of one or more subclasses of vasopressin receptors. The compounds can be selective modulators of one or more subclasses of vasopressin receptors. Compounds of the invention can be used in the treatment of a condition wherein modulating a vasopressin receptor is medically indicated for treatment of the condition.

Disclosed herein are immunoconjugates comprising an inhibitor of Eg5 linked to an antigen binding moiety such as an antibody, that are useful for treating cell proliferative disorders. Also disclosed are novel inhibitors of Eg5 that can be used either alone or as part of an immunoconjugate to treat cell proliferation disorders. The Eg5 inhibitors include compounds of this formula as described herein:

##STR00001##

The invention further provides pharmaceutical compositions comprising these compounds and immunoconjugates, and compositions comprising the immunoconjugates or compounds with a therapeutic co-agent, and methods to use these compounds, conjugates and compositions for treating cell proliferation disorders.

Disclosed herein are immunoconjugates comprising an inhibitor of Eg5 linked to an antigen binding moiety such as an antibody, that are useful for treating cell proliferative disorders. Also disclosed are novel inhibitors of Eg5 that can be used either alone or as part of an immunoconjugate to treat cell proliferation disorders. The Eg5 inhibitors include compounds of this formula as described herein:

##STR00001##

The invention further provides pharmaceutical compositions comprising these compounds and immunoconjugates, and compositions comprising the immunoconjugates or compounds with a therapeutic co-agent, and methods to use these compounds, conjugates and compositions for treating cell proliferation disorders.

The present invention relates to a new process for the preparation of Tetraconazole or one of its optically active isomers by means of the fluorination of 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-1-ol.

The present invention relates to a new process for the preparation of Tetraconazole or one of its optically active isomers by means of the fluorination of 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-1-ol.

A method for producing a 1,2,4-triazole compound involves reacting an amide compound represented by formula (2) with a hydrazide compound represented by formula (3) in a solvent in the presence of a Lewis acid and a Lewis base, thereby obtaining a 1,2,4-triazole compound represented by formula (1):

##STR00001##

R.sup.1 represents an alkyl group, a cycloalkyl group, an alkoxy group, a cycloalkoxy group, an aryl group, an aryloxy group, a monovalent heterocyclic group or a substituted amino group, R.sup.2 and R.sup.3 each independently represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a monovalent heterocyclic group or a substituted amino group, and Ring A and Ring B each independently represent an aromatic hydrocarbon ring or an aromatic heterocyclic ring.

A method for producing a 1,2,4-triazole compound involves reacting an amide compound represented by formula (2) with a hydrazide compound represented by formula (3) in a solvent in the presence of a Lewis acid and a Lewis base, thereby obtaining a 1,2,4-triazole compound represented by formula (1):

##STR00001##

R.sup.1 represents an alkyl group, a cycloalkyl group, an alkoxy group, a cycloalkoxy group, an aryl group, an aryloxy group, a monovalent heterocyclic group or a substituted amino group, R.sup.2 and R.sup.3 each independently represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a monovalent heterocyclic group or a substituted amino group, and Ring A and Ring B each independently represent an aromatic hydrocarbon ring or an aromatic heterocyclic ring.

The invention provides for compounds of formula I: wherein Z is absent or (CR.sub.AR.sub.B).sub.nW; each RA and RB is independently (i) H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, haloalkyl, each of which may be optionally substituted; (ii) OH, ORc, NH2, NHR.sub.c, NR.sub.cR.sub.c, SH, S(O).sub.mR.sub.c; or (iii) R.sub.A and R.sub.B together form C(O); W is absent, C(O), C(O)O, C(O)NR.sub.cR.sub.c, O, S(O).sub.m, or NR.sub.cR.sub.c; Y is an optionally substituted heterocyclic, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aryl, or NR.sub.XR.sub.Y; wherein R.sub.x and R.sub.y are each independently H, alkyl or aryl; X.sup.1 is selected from the group consisting of halogen, methyl, and hydroxyl; X2 is a halogen; each R.sub.c is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which may be optionally substituted; m is O, 1, or 2; and n is 1, 2, 3, 4, 5, or 6; and pharmaceutically acceptable salts thereof. ##STR00001##

The invention provides for compounds of formula I: wherein Z is absent or (CR.sub.AR.sub.B).sub.nW; each RA and RB is independently (i) H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, haloalkyl, each of which may be optionally substituted; (ii) OH, ORc, NH2, NHR.sub.c, NR.sub.cR.sub.c, SH, S(O).sub.mR.sub.c; or (iii) R.sub.A and R.sub.B together form C(O); W is absent, C(O), C(O)O, C(O)NR.sub.cR.sub.c, O, S(O).sub.m, or NR.sub.cR.sub.c; Y is an optionally substituted heterocyclic, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aryl, or NR.sub.XR.sub.Y; wherein R.sub.x and R.sub.y are each independently H, alkyl or aryl; X.sup.1 is selected from the group consisting of halogen, methyl, and hydroxyl; X2 is a halogen; each R.sub.c is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which may be optionally substituted; m is O, 1, or 2; and n is 1, 2, 3, 4, 5, or 6; and pharmaceutically acceptable salts thereof. ##STR00001##