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US 8,940,735 B2Granted
Metalloenzyme inhibitor compounds
AssigneeViamet Pharmaceuticals, Inc.
InventorsWilliam J. Hoekstra, Robert J. Schotzinger, Gary D. Gustafson
Life of this patent
Estimating the term…
Abstract
The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.
Claims22
A method of treating a metalloenzyme-mediated disease or disorder in or on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
- MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
- R1 is H, halo, alkyl or haloalkyl;
- R2 is H, halo, alkyl or haloalkyl;
- R3 1,1′-biphenyl substituted with 4′—OCH2CF3 or 4′-F, or heteroaryl, which may be optionally substituted with 1, 2 or 3 independent R5;
- R4 is aryl, heteroaryl or cycloalkyl, optionally substituted with 0, 1, 2 or 3 independent R6;
- each R5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R6, heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, halocycloalkyl, thioalkyl, SF3, SF6, SCN, SO2R7, C(O)alkyl, C(O)OH, C(O)Oalkyl;
- each R6 is independently alkyl, thioalkyl, cyano, haloalkyl, hydroxyl, alkoxy, halo, haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl, SF3, SF6, SCN, SO3H;
- and SO2R7;
- R7 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R8 is H, —Si(R9)3, —P(O)(OH)2, —CH2—O—P(O)(OH)2, or —C(O)alkyl optionally substituted with amino;
- R9 is independently alkyl or aryl;
- wherein R3 is not optionally substituted monocyclic pyridyl optionally substituted with 1, 2 or 3 independent R5;
- and
- the metalloenzyme-related disorder or disease is mediated by lanosterol demethylase (CYP51).
11 more elements
A method of inhibiting metalloenzyme activity in a microorganism on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
- MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
- R1 is H, halo, alkyl or haloalkyl;
- R2 is H, halo, alkyl or haloalkyl;
- R3 is 1,1′-biphenyl substituted with 4′—OCH2CF3 or 4′—F, or heteroaryl, which may be optionally substituted with 1, 2 or 3 independent R5;
- R4 is aryl, heteroaryl or cycloalkyl, optionally substituted with 0, 1, 2or 3 independent R6;
- each R5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R6, heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, halocycloalkyl, thioalkyl, SF3, SF6, SCN, SO2R7, C(O)alkyl, C(O)OH, C(O)Oalkyl;
- each R6 is independently alkyl, thioalkyl, cyano, haloalkyl, hydroxyl, alkoxy, halo haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl, SF3, SF6, SCN, SO3H;
- and SO2R7;
- R7 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R8 is H, —Si(R9)3, —P(O)(OH)2, —CH2—O—P(O)(OH)2, or —C(O)alkyl optionally substituted with amino;
- R9 is independently alkyl or aryl;
- wherein R3 is not optionally substituted monocyclic pyridyl optionally substituted with 1, 2or 3 independent R5;
- and
- wherein the metalloenzyme is lanosterol demethylase (CYP51).
11 more elements
A method of treating a fungal disease or disorder in or on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
- MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
- R1 is H, halo, alkyl or haloalkyl;
- R2 is H, halo, alkyl or haloalkyl;
- R3 is 1,1′-biphenyl substituted with 4′—OCH2CF3 or 4′—F, or heteroaryl, which may be optionally substituted with 1, 2 or 3 independent R5;
- R4 is aryl, heteroaryl or cycloalkyl, optionally substituted with 0, 1, 2or 3 independent R6;
- each R5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R6, heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, halocycloalkyl, thioalkyl, SF3 , SF6, SCN, SO2R7, C(O)alkyl, C(O)OH, C(O)Oalkyl;
- each R6 is independently alkyl, thioalkyl, cyano, haloalkyl, hydroxyl, alkoxy, halo haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl, SF3, SF6, SCN, SO3H;
- and SO2R7;
- R7 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R8 is H, —Si(R9)3, —P(O)(OH)2, —CH2—O—P(O)(OH)2, or —C(O)alkyl optionally substituted with amino;
- R9 is independently alkyl or aryl;
- and
- wherein R3 is not optionally substituted monocyclic pyridyl optionally substituted with 1, 2or 3 independent R5.
10 more elements
A method of treating fungal growth in or on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
- MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
- R1 is H, halo, alkyl or haloalkyl;
- R2 is H, halo, alkyl or haloalkyl;
- R3 is 1,1′-biphenyl substituted with 4′—OCH2CF3 or 4′—F, or heteroaryl, which may be optionally substituted with 1, 2 or 3 independent R5;
- R4 is aryl, heteroaryl or cycloalkyl, optionally substituted with 0, 1, 2or 3 independent R6;
- each R5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R6, heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, halocycloalkyl, thioalkyl, SF3 , SF6, SCN, SO2R7, C(O)alkyl, C(O)OH, C(O)Oalkyl;
- each R6 is independently alkyl, thioalkyl, cyano, haloalkyl, hydroxyl, alkoxy, halo haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl, SF3, SF6, SCN, SO3H;
- and SO2R7;
- R7 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R8 is H, —Si(R9)3, —P(O)(OH)2, —CH2—O—P(O)(OH)2, or —C(O)alkyl optionally substituted with amino;
- R9 is independently alkyl or aryl;
- and
- wherein R3 is not optionally substituted monocyclic pyridyl optionally substituted with 1, 2 or 3 independent R5.
10 more elements
A method of inhibiting microorganisms in or on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
- MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
- R1 is H, halo, alkyl or haloalkyl;
- R2 is H, halo, alkyl or haloalkyl;
- R3 is 1,1′-biphenyl substituted with 4′—OCH2CF3 or 4′—F, or heteroaryl, which may be optionally substituted with 1, 2 or 3 independent R5;
- R4 is aryl, heteroaryl or cycloalkyl, optionally substituted with 0, 1, 2 or 3 independent R6;
- each R5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R6, heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, halocycloalkyl, thioalkyl, SF3 , SF6, SCN, SO2R7, C(O)alkyl, C(O)OH, C(O)Oalkyl;
- each R6 is independently alkyl, thioalkyl, cyano, haloalkyl, hydroxyl, alkoxy, halo haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl, SF3, SF6, SCN, SO3H;
- and SO2R7;
- R7 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R8 is H, —Si(R9)3, —P(O)(OH)2, —CH2—O—P(O)(OH)2, or —C(O)alkyl optionally substituted with amino;
- R9 is independently alkyl or aryl;
- and
- wherein R3 is not optionally substituted monocyclic pyridyl optionally substituted with 1, 2 or 3 independent R5;
- and
- wherein the microorganism belongs to at least one genera selected from Blumeria, Podospaera, Sphaerotheca, Unicinula, Erysiphe, Puccinia, Phakopspora, Gymnosporangium, Hemileia, Uromyces, Alternia, Cercospora, Cladosporium, Cochliobolus, Colletotrichum, Magnaporthe, Mycosphaerella, Phaeosphaeria, Pyrenophora, Ramularia, Rhyncosporium, Septoria, Venturia, Ustilago, Aspergillus, Penicillium, Drechslera, Fusarium, Botrytis, Gibberella, Rhizoctonia, Pseudocercosporella, Sclerotinia, Helminithosporium, Stagonospora, Exserohilum, and Pyricularia.
12 more elements
A composition comprising a compound of Formula I or salt thereof, wherein:
- MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
- R1 is H, halo, alkyl or haloalkyl;
- R2 is H, halo, alkyl or haloalkyl;
- R3 is 1,1′-biphenyl substituted with 4′—OCH2CF3 or 4′—F, or heteroaryl, which may be optionally substituted with 1, 2 or 3 independent R5;
- R4 is aryl, heteroaryl or cycloalkyl, optionally substituted with 0, 1, 2 or 3 independent R6;
- each R5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R6, heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, halocycloalkyl, thioalkyl, SF3 , SF6, SCN, SO2R7, C(O)alkyl, C(O)OH, C(O)Oalkyl;
- each R6 is independently alkyl, thioalkyl, cyano, haloalkyl, hydroxyl, alkoxy, halo haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl, SF3, SF6, SCN, SO3H;
- and SO2R7;
- R7 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R8 is H, —Si(R9)3, —P(O)(OH)2, —CH2—O—P(O)(OH)2, or —C(O)alkyl optionally substituted with amino;
- R9 is independently alkyl or aryl;
- and
- wherein R3 is not optionally substituted monocyclic pyridyl optionally substituted with 1, 2 or 3 independent R5, said composition further comprising an azole fungicide selected from epoxiconazole, tebuconazole, fluquinconazole, flutriafol, metaconazole, myclobutanil, cycproconazole, prothioconazole and propiconazole.
10 more elements
A composition comprising a compound of Formula I, or salt thereof, wherein:
- MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
- R1 is H, halo, alkyl or haloalkyl;
- R2 is H, halo, alkyl or haloalkyl;
- R3 is 1,1′-biphenyl substituted with 4′—OCH2CF3 or 4′—F, or heteroaryl, which may be optionally substituted with 1, 2 or 3 independent R5;
- R4 is aryl, heteroaryl or cycloalkyl, optionally substituted with 0, 1, 2or 3 independent R6;
- each R5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R6, heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, halocycloalkyl, thioalkyl, SF3 , SF6, SCN, SO2R7, C(O)alkyl, C(O)OH, C(O)Oalkyl;
- each R6 is independently alkyl, thioalkyl, cyano, haloalkyl, hydroxyl, alkoxy, halo haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl, SF3, SF6, SCN, SO3H;
- and SO2R7;
- R7 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R8 is H, —Si(R9)3, —P(O)(OH)2, —CH2—O—P(O)(OH)2, or —C(O)alkyl optionally substituted with amino;
- R9 is independently alkyl or aryl;
- and
- wherein R3 is not optionally substituted monocyclic pyridyl optionally substituted with 1, 2 or 3 independent R5, said composition further comprising a strobilurin fungicide from the group trifloxystrobin, pyraclostrobin, orysastrobin, fluoxastrobin and azoxystrobin.
10 more elements
A method of inhibiting microorganisms in or on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
- MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
- R1 is H, halo, alkyl or haloalkyl;
- R2 is H, halo, alkyl or haloalkyl;
- R3 is 1,1′-biphenyl substituted with 4′—OCH2CF3 or 4′—F, or heteroaryl, which may be optionally substituted with 1, 2 or 3 independent R5;
- R4 is aryl, heteroaryl or cycloalkyl, optionally substituted with 0, 1, 2or 3 independent R6;
- each R5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R6, heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, halocycloalkyl, thioalkyl, SF3, SF6, SCN, SO2R7, C(O)alkyl, C(O)OH, C(O)Oalkyl;
- each R6 is independently alkyl, thioalkyl, cyano, haloalkyl, hydroxyl, alkoxy, halo haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl, SF3, SF6, SCN, SO3H;
- and SO2R7;
- R7 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R8 is H, —Si(R9)3, —P(O)(OH)2, —CH2—O—P(O)(OH)2, or —C(O)alkyl optionally substituted with amino;
- R9 is independently alkyl or aryl;
- and
- wherein R3 is not optionally substituted monocyclic pyridyl optionally substituted with 1, 2 or 3 independent R5;
- and
- wherein the microorganism is selected from the group consisting of Venturia inaequalis, Septoria tritici, Cercospora beticola, Cercospora arachidicola, Colletotrichum lagenarium, Puccinia graminis f. sp. tritici, Puccinia recondite tritici, Uncinula necoator, Blumeria grammis, and Mycosphaerella fijiensis.
12 more elements
Dependencies are inferred from the claim text.