Boronic and Borinic Acid Compound as Inhibitors of Sulfenic Acid-Containing Proteins,申请号US201414576613-传众专利搜索

Boronic and Borinic Acid Compound as Inhibitors of Sulfenic Acid-Containing Proteins

申请公布号：US2015140635(A1)

申请号：US201414576613

申请日期：2014.12.19

申请公布日期：2015.05.21

申请人：

Benkovic Stephen;Liu Chunyu;Tomsho John W.

发明人：Benkovic Stephen;Liu Chunyu;Tomsho John W.

分类号：C12N9/99

主分类号：C12N9/99

地址：State College PA US

摘要：A boronic or borinic acid compound is used to inhibit the activity of a sulfenic acid-containing protein. Thus, a biologically-active sulfenic acid-containing protein is contacted with an activity-inhibiting effective amount of a boronic or borinic acid compound of Formula I or a salt, hydrate or solvate thereof, whose components are disclosed within, and that contact is maintained for a time sufficient to inhibit the biological activity of the protein.;

主权项：1. A method of inhibiting the biologic activity of a biologically-active sulfenic acid-containing protein that comprises the step of contacting said protein with an activity-inhibiting effective amount of a boronic acid or borinic acid compound of Formula I or a salt, hydrate, or solvate thereof, and maintaining that contact for a time sufficient to inhibit the activity of that proteinwherein A is oxygen (O) when p is 1 and bond a is present, or R7 or OR7 when bond a is absent and p is 0; B is boron; V is CH2 when p is 1 and bonds a and b are present, and absent when p is 0 and bonds a and b are absent; E is N, or CR2; G is N, or CR3; W is N, C, or CR4; X is N or CR5; Y is N or CR6; Z═O (oxygen) or (CH2)nC(═O)O, where n=0, 1 or 2, and m=0 or 1 such that Z is absent when m=0 and B is bonded directly to the aromatic or heteroaromatic ring, Ar1; p=0 (zero) or 1, with the proviso that when p is 1, W is C, bonds a and b are present and m is 0, and when p is zero (0), all three of V, bond a and bond b are absent, m=one, and W is N or CR4; m=is 0 or 1; m is 0 when p is 1, and m is 1 when p is 0, with the proviso that when m=1 at least one of A and R* is other than OR7 and OR1, respectively; R* is R1 or OR1; R1 and R7 are selected independently from the group consisting of hydrido (hydrogen), optionally substituted C1-C8 hydrocarbyl, optionally substituted aryl, arC1-C8 hydrocarbyl, and optionally substituted heteroaryl, wherein said optional substituents are selected from the group consisting of C1-C8 hydrocarbyl, aryl, arC1-C8 hydrocarbyl, heteroaryl, heteroarC1-C8 hydrocarbyl, heterocyclyl, cyclohydrocarbyloxy, heterocyclyloxy, —C(O)-aryl, hydrocarbyloxy, aryloxy, heteroaryloxy, —OC(O)—(C1-C8 hydrocarbyl), —OCH2CH2OH, —O(CH2)3CO2H, 2-(morpholino)ethoxy, —(CH2)kOH (where k=1, 2 or 3), —CH2NH2, —CH2NH(C1-C8 hydrocarbyl), —CH2N(C1-C8 hydrocarbyl)2, halogen, formyl (—CHO), thioformyl (—CHS), —CH═NOH, —CO2H, thiocarboxyl (—CSOH), sulfonyl (—HSO2), C1-C8 hydrocarbylsulfonyl, arylsulfonyl, heteroarylsulfonyl, C1-C8 hydrocarbylsulfinyl, arylsulfinyl, heteroarylsulfinyl, —CO2(C1-C8 hydrocarbyl, —C(O)NH2, —C(O)NH(C1-C8 hydrocarbyl), —CON(C1-C8 hydrocarbyl)2, —OH, —SH, —S—(C1-C8 hydrocarbyl), —S-aryl, —SO2(C1-C8 hydrocarbyl), —SO2N(C1-C8 hydrocarbyl)2, C1-C8 hydrocarbyl-sulfonylamino (—SO2NH C1-C8 hydrocarbyl), aryl sulfonylamino, —SO2NH2, —SO3H, —SCF3, —CN, —CHF2, —CF3, —NO2, amino (—NH2), —NH(C1-C8 hydrocarbyl, —N(C1-C8 hydrocarbyl)2, arylamino, diarylamino, —NHSO2(C1-C8 hydrocarbyl), —C(O)NH(C1-C8 hydrocarbyl), and —C(O)N(C1-C8 hydrocarbyl)2; R2, R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen (hydrido), C1-C8 hydrocarbyl, aryl, arC1-C8 hydrocarbyl, heteroaryl, heteroarC1-C8 hydrocarbyl, heterocyclyl, cyclohydrocarbyloxy, heterocyclyloxy, —C(O)-aryl, hydrocarbyloxy, aryloxy, heteroaryloxy, —OC(O)—(C1-C8 hydrocarbyl), —OCH2CH2OH, —O(CH2)3CO2H, 2-(morpholino)ethoxy, —(CH2)kOH (where k=1, 2 or 3), —CH2NH2, —CH2NH(C1-C8 hydrocarbyl), —CH2N(C1-C8 hydrocarbyl)2, halogen, formyl (—CHO), thioformyl (—CHS), —CH═NOH, —CO2H, thiocarboxyl (—CSOH), sulfonyl (—HSO2), C1-C8 hydrocarbylsulfonyl, arylsulfonyl, heteroarylsulfonyl, C1-C8 hydrocarbylsulfinyl, arylsulfinyl, heteroarylsulfinyl, —CO2(C1-C8 hydrocarbyl), —C(O)NH2, —C(O)NH(C1-C8 hydrocarbyl), —CON(C1-C8 hydrocarbyl)2, —OH, —SH, —S—(C1-C8 hydrocarbyl), —S-aryl, —SO2(C1-C8 hydrocarbyl), —SO2N(C1-C8 hydrocarbyl)2, C1-C8 hydrocarbyl-sulfonylamino (—SO2NH C1-C8 hydrocarbyl), aryl sulfonylamino, —SO2NH2, —SO3H, —SCF3, —CN, —CHF2, —CF3, —NO2, amino (—NH2), —NH(C1-C8 hydrocarbyl), —N(C1-C8 hydrocarbyl)2, arylamino, diarylamino, —NHSO2(C1-C8 hydrocarbyl), —CONH(C1-C8 hydrocarbyl), and —C(O)N(C1-C8 hydrocarbyl)2, wherein said C1-C8 hydrocarbyl, aryl, arC1-C8 hydrocarbyl, heteroaryl, heteroarC1-C8 hydrocarbyl, cyclohydrocarbyl and heterocyclic groups in each of the R2, R3, R4, R5 and R6 (R2-6) substituents are themselves optionally substituted and wherein said optional substituents are selected from the group consisting of C1-C8 hydrocarbyl, aryl, arC1-C8 hydrocarbyl, heteroaryl, heteroarC1-C8 hydrocarbyl, heterocyclyl, cyclohydrocarbyloxy, heterocyclyloxy, —C(O)-aryl, hydrocarbyloxy, aryloxy, heteroaryloxy, —OC(O)—(C1-C8 hydrocarbyl), —OCH2CH2OH, —O(CH2)3CO2H, 2-(morpholino)ethoxy, —(CH2)kOH (where k=1, 2 or 3), —CH2NH2, —CH2NH(C1-C8 hydrocarbyl), —CH2N(C1-C8 hydrocarbyl)2, halogen, formyl (—CHO), thioformyl (—CHS), —CH═NOH, —CO2H, thiocarboxyl (—CSOH), sulfonyl (—HSO2), C1-C8 hydrocarbylsulfonyl, arylsulfonyl, heteroarylsulfonyl, C1-C8 hydrocarbylsulfinyl, arylsulfinyl, heteroarylsulfinyl, —CO2(C1-C8 hydrocarbyl, —C(O)NH2, —C(O)NH(C1-C8 hydrocarbyl), —CON(C1-C8 hydrocarbyl)2, —OH, —SH, —S—(C1-C8 hydrocarbyl), —S-aryl, —SO2(C1-C8 hydrocarbyl), —SO2N(C1-C8 hydrocarbyl)2, C1-C8 hydrocarbylsulfonylamino (—SO2NH C1-C8 hydrocarbyl), aryl sulfonylamino, —SO2NH2, —SO3H, —SCF3, —CN, —CHF2, —CF3, —NO2, amino (—NH2), —NH(C1-C8 hydrocarbyl, —N(C1-C8 hydrocarbyl)2, arylamino, diarylamino, —NHSO2(C1-C8 hydrocarbyl), —C(O)NH(C1-C8 hydrocarbyl), and —C(O)N(C1-C8 hydrocarbyl)2.