Multiheteroaryl compounds as inhibitors of h-pgds and their use for treating prostaglandin d2 mediated diseases

A compound of Formula (I):

• wherein:
• R1 is (C1-C6)-alkyl, (C3-C6)-cycloalkyl, phenyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl;
• wherein each phenyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl of R1 may be optionally substituted with no more than two of each or a combination of fluoro, hydroxy, —CH2OH, carboxy, carboxymethyl, or carboxyethyl;
• R2 is —(CH2)nZ1 or —(CH2)nZ2;
• n is 0, 1, 2, 3, or 4;
• Z1 is hydrogen, OR3, C(O)R3, CO2R3, C(O)NR4R5, SO2NR4R5, SO2R3, (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C3-C6)-alkenyl, (C3-C6)-alkynyl, (C6-C14)-aryl, (CH2)pCF3, a five- to ten-membered heteroaryl,
• or a three- to ten-membered heterocycle;
• wherein any one nitrogen atom of any heterocycle containing one or more nitrogen atoms that may be substituted with a non-ring atom are substituted with —(CH2)qQ;
• Z2 is cyano, trifluoromethyl, (CF2)pCF3, SR3, NR4R5, N(H)C(O)R3, N(H)CO2R3, N(H)C(O)NR4R5, N(H)SO2R3, vinyl, or ethynyl when n is 1, 2, 3 or 4;
• Z2 may also be cyano, trifluoromethyl, (CF2)pCF3, SR3, NR4R5, N(H)C(O)R3, N(H)CO2R3, N(H)C(O)NR4R5, N(H)SO2R3, vinyl, or ethynyl when n is 0, except when R2 is covalently bonded to a U1, U2, U3, or U4 that is a nitrogen atom;
• R3 is hydrogen, (C1-C6)-alkyl, trifluoromethyl, (C3-C6)-alkenyl, (C3-C6-alkynyl, (CH2)m(C3-C6)-cycloalkyl, (CH2)mphenyl, (CH2)m-(five- to ten-membered heteroaryl), or (CH2)m(three- to ten-membered heterocycle), wherein any one nitrogen atom of any heterocycle containing one or more nitrogen atoms that may be substituted with a non-ring atom are substituted with —(CH2)qQ;
• m is 0, 1, 2, 3, or 4;
• q is 0, 1, 2, 3, or 4;
• Q is hydrogen, (C1-C6)-alkyl, (CH2)pCF3, (C3-C6)-alkenyl, (C3-C6)-alkynyl, (C3-C6)-cycloalkyl, (C6-C14-aryl, C(O)R3, CO2R3, C(O)NR4R5, a three- to six-membered heterocycle, or a five- to ten-membered heteroaryl when q is 0, 1, 2, 3, or 4;
• Q may also be cyano, trifluoromethyl, or SO2NR4R5 when q is 1, 2, 3, or 4;
• Q may also be hydroxy, (C1-C6)-alkoxy, sulfhydryl, —S—(C1-C6)-alkyl, or NR4R5 when q is 2, 3, or 4;
• p is 1, 2, or 3;
• R3 may also be vinyl or ethynyl when R3 is not covalently bonded to an N or O atom;
• R3 may also be vinyl or ethynyl when R3 is not covalently bonded to an S atom possessing a −2 (minus 2) oxidation state;
• R4 and R5 are independently hydrogen, (C1-C6)-alkyl, (C3-C6)-alkenyl, (C3-C6)-alkynyl, (CH2)m(C3-C6)-cycloalkyl, (CH2)mphenyl, (CH2)m-(three- to ten-membered heterocycyl), or (CH2)m-(five- to ten-membered heteroaryl);
• the NR4R5 group of any C(O)NR4R5, SO2NR4R5, NR4R5, or N(H)C(O)NR4R5 may also form a pyrrolidine, a piperidine, a morpholine, a thiomorpholine, or a thiomorpholine S-dioxide;
• the NR4R5 group of any C(O)NR4R5, SO2NR4R5, NR4R5, or N(H)C(O)NR4R5 may also form a piperazine ring, wherein the other nitrogen atom of the piperazine ring is substituted with hydrogen, (C1-C6)-alkyl, CH2CF3, (C3-C6)-cycloalkyl, CH2(C3-C6)-cycloalkyl, phenyl, benzyl, hydroxyethyl, or hydroxypropyl;
• phenyl or heteroaryl rings of Z1 and Z2 are optionally substituted with one-to-three of any one or combination of the following:
• halo, hydroxy, sulfhydryl, (C1-C3)-alkoxy, (C1-C3)-alkyl, (C1-C3)-alkylthio, trifluoromethyl, trifluoromethoxy, cyano, carboxy, carboxy(C1-C3)-alkyl, carbamoyl, or sulfamoyl;
• W is a covalent bond, O, S, SO, SO2, CH2, CHOH, CO, or NH;
• U1, U2, U3, U4, and a carbon atom form a five-membered heteroaryl ring;
• wherein one of U1, U2, U3, and U4 of the five-membered heteroaryl ring is covalently bonded to the R2 group;
• wherein the U1, U2, U3, or U4 that is covalently bonded to the R2 group is a carbon atom or a nitrogen atom;
• wherein when the U1, U2, U3, or U4 that is covalently bonded to the R2 group is a nitrogen atom, one, two, or all of the other three of the group consisting of U1, U2, U3, and U4 is N and each remaining of the group consisting of U1, U2, U3, and U4 that is not N is C—R6;
• wherein when the U1, U2, U3, or U4 that is covalently bonded to the R2 group is a carbon atom, one of the other three of the group consisting of U1, U2, U3, and U4 is N—R6, O, or S, and each of remaining of the group consisting of U1, U2, U3, and U4 is C—R6 or N;
• Y1, Y2, Y3, a nitrogen atom, and two carbon atoms form a six-membered heteroaryl ring;
• wherein no more than one of the group consisting of Y1, Y2, and Y3 is N;
• and wherein all Y1, Y2, and Y3 that are not N are C—R6;
• each R6 is independently hydrogen, methyl, trifluoromethyl, or amino;
• and
• each R7 is independently hydrogen or methyl;
• or an equivalent thereof, or a hydrate, solvate, or N-oxide thereof, or a pharmaceutically acceptable salt thereof.