Cyclopropyl compounds as ccr5 antagonists

A compound of formula (I):

• or a pharmaceutically acceptable salt, solvate, or derivative thereof, wherein:
• X is a C1-5 alkylene chain, wherein said X is optionally substituted by one or more ═O, ═S, —S(O)t—, alkyl, or halogen and wherein said C1-5 alkylene chain may optionally have 0-3 heteroatoms selected from oxygen, phosphorus, sulfur, or nitrogen;
• Ring A is a saturated, partially saturated or aromatic 3-7 monocyclic or 8-10 membered bicyclic ring having one ring nitrogen and 0-4 additional heteroatoms selected from oxygen, phosphorus, sulfur, or nitrogen;
• R1 is selected from the group consisting of
• (a) a saturated, partially saturated, or aromatic 4-7 monocyclic or 8-10 membered bicyclic ring having one ring nitrogen and 0-4 additional heteroatoms selected from oxygen, phosphorus, sulfur, or nitrogen, optionally attached through a C1-6 alkylene chain, and optionally substituted by one or more R8;
• Q is carbon, oxygen, or S(O)t;
• w is 1 or 2;
• each R2 is independently selected from the group consisting of —OR0, —C(O)—R0, —S(O)2—R0, —C(O)—N(R0)2, —S(O)2—N(R0)2, —(CH2)a—N(R0)(—Vb—R+), —(CH2)a—(—Vb—R+), halogen, alkyl optionally substituted by one or more R7, alkenyl optionally substituted by one or more R7, alkynyl optionally substituted by one or more R7, aryl optionally substituted by one or more R6, heteroaryl optionally substituted by one or more R6, cycloalkyl optionally substituted by one or more R8, and heterocyclyl optionally substituted by one or more R8;
• and two adjacent R2s on Ring A are optionally taken together to form a fused, saturated, partially saturated or aromatic 5-6 membered ring having 0-3 heteroatoms selected from oxygen, phosphorus, sulfur, or nitrogen;
• or two geminal R2s are optionally taken together to form a spiro, saturated, partially saturated or aromatic 5-6 membered ring having 0-3 heteroatoms selected from oxygen, phosphorus, sulfur, or nitrogen, said fused or spiro ring being optionally substituted by one or more R8;
• each a independently is 0-3;
• each b independently is 0 or 1;
• V is —C(O)—, —C(O)O—, —S(O)2—, or —C(O)—N(R0)—;
• R+ is alkyl, cycloalkyl, aralkyl, aryl, heteroaryl, heteroaralkyl, or heterocyclyl, wherein said R+ is optionally substituted by one or more R8;
• d is 0-3
• m is 0 or 1;
• n is 0-5;
• R3 is H, —N(R0)2, —N(R0)C(O)R0, —CN, halogen, CF3, alkyl optionally substituted by one or more groups selected from R7 or —S-aryl optionally substituted by —(CH2)1-6—N(R0)SO2(R0), alkenyl optionally substituted by one or more groups selected from R7 or —S-aryl optionally substituted by —(CH2)1-6—N(R0)SO2(R0), alkynyl optionally substituted by one or more groups selected from R7 or —S-aryl optionally substituted by —(CH2)1-6—N(R0)SO2(R0), cycloalkyl or carbocyclyl optionally substituted by one or more R8, aryl optionally substituted by one or more R6, heteroaryl optionally substituted by one or more R6, or heterocyclyl optionally substituted by one or more R8;
• Y is alkyl, alkenyl, alkynyl, —(CR4R5)p—, —C(O)—, —C(O)C(O)—, —C(S)—, —O—(CH2)04—C(O)—, —(CH2)04—C(O)—O—, —N(R0)—C(O)—, —C(O)—N(R0)—, —N(R0)—C(S)—, —S(O)t—, —O—C(═N—CN)—, —O—C(═N—R0)—, —C(═N—CN)—O—, —C(═N—CN)—S—, —C(═N—R0)—O—, —S—C(═N—CN)—, —N(R0)—C(═N—CN)—, —C(═N—CN)—, —N(R0)—C[═N—C(O)—R0], —N(R0)—C[═N—S(O)t—R0], —N(R0)—C(═N—OR0)—, —N(R0)—C(═N—R0)—, or —C(═N—R0)—;
• each R4 is independently H or alkyl optionally substituted by R7, alkenyl optionally substituted by R7, or alkynyl optionally substituted by R7;
• each R5 is independently selected from the group consisting of H, —C(O)—OR6, —C(O)—N(R0)2, —S(O)t—N(R0)2, —S(O)t—R0, aryl optionally substituted by R6, and heteroaryl optionally substituted by R6;
• p is 1-5;
• each t independently is 1 or 2;
• each R6 is independently selected from the group consisting of halogen, —CF3, —OCF3, —OR0, —(CH2)1-6—OR0, —SR0, —(CH2)1-6—SR0, —SCF3, —R0, methylenedioxy, ethylenedioxy, —NO2, —CN, —(CH2)1-6—CN, —N(R0)2, —(CH2)1-6—N(R0)2, —NR0C(O)R0, —NR0(CN), —NR0C(O)N(R0)2, —NR0C(S)N(R0)2, —NR0CO2R0, —NR0NR0C(O)R0, —NR0NR0C(O)N(R0)2, —NR0NR0CO2R0, —C(O)C(O)R0, —C(O)CH2C(O)R0, —(CH2)0-6CO2R0, —O—C(O)R0, —C(O)R0, —C(O)N(R0)N(R0)2, —C(O)N(R0)2, —C(O)N(R0)OH, —C(O)N(R0)SO2R0, —OC(O)N(R0)2, —S(O)tR0, —S(O)t—OR0, —S(O)tN(R0)C(O)R0, —S(O)tN(R0)OR0, —NR0SO2N(R0)2, —NR0SO2R0, —C(═S)N(R0)2, —C(═NH)—N(R0)2, —(CH2)1-6—C(O)R0, —C(═N—OR0)—N(R0)2, —O—(CH2)0-6—SO2N(R0)2, —(CH2)1-6NHC(O)R0, and —SO2N(R0)2 wherein the two R0s on the same nitrogen are optionally taken together to form a 5-8 membered saturated, partially saturated, or aromatic ring having additional 0-4 heteroatoms selected from oxygen, phosphorus, nitrogen, or sulfur;
• each R7 is independently selected from the group consisting of halogen, —CF3, —R0, —OR0, —OCF3, —(CH2)1-6—OR0, —SR0, —SCF3, —(CH2)1-6—SR0, aryl optionally substituted by R6, methylenedioxy, ethylenedioxy, —NO2, —CN, —(CH2)1-6—CN, —N(R0)2, —(CH2)1-6—N(R0)2, —NR0C(O)R0, —NR0(CN), —NR0C(O)N(R0)2, —N(R0)C(S)N(R0)2, —NR0CO2R0, —NR0NR0C(O)R0, —NR0NR0C(O)N(R0)2, —NR0NR0CO2R0, —C(O)C(O)R0, —C(O)CH2C(O)R0, —(CH2)0-6—CO2R0, —C(O)R0, —C(O)N(R0)N(R0)2, —C(O)N(R0)2, —C(O)N(R0)OH, —OC(O)R0, —C(O)N(R0)SO2R0, —OC(O)N(R0)2, —S(O)tR0, —S(O)t—OR0, —S(O)tN(R0)C(O)R0, —S(O)tN(R0)OR0, —NR0SO2N(R0)2, —NR0SO2R0, —C(═S)N(R0)2, —C(═NH)—N(R0)2, —(CH2)1-6—C(O)R0, —C(═N—OR0)—N(R0)2, —O—(CH2)0-6—SO2N(R0)2, —(CH2)1-6—NHC(O)R0, and —SO2N(R0)2 wherein the two R0s on the same nitrogen are optionally taken together to form a 5-8 membered saturated, partially saturated, or aromatic ring having additional 0-4 heteroatoms selected from oxygen, phosphorus, nitrogen, or sulfur;
• each R8 is independently selected from the group consisting of R7, ═O, ═S, ═N(R0), and ═N(CN);
• each R9 independently is hydrogen, alkyl optionally substituted by one or more R7, alkenyl optionally substituted by one or more R7, alkynyl optionally substituted by one or more R7, cycloalkyl optionally substituted by one or more R8, heterocyclyl optionally substituted by one or more R8, heteroaryl optionally substituted by one or more R6, or aryl optionally substituted by one or more R6;
• or
• —(Y)m—R3 and R9 may combined with the nitrogen atom with which they are attached to form a saturated, partially saturated, or aromatic 5-7 membered monocyclic or 8-10 membered bicyclic ring that optionally contains 1 to 3 additional heteroatoms selected oxygen, phosphorus, sulfur, or nitrogen, wherein said ring may be optionally substituted with one or more R8;
• R10 is hydrogen, alkyl optionally substituted by one or more R7, alkenyl optionally substituted by one or more R7, alkynyl optionally substituted by one or more R7, cycloalkyl optionally substituted by one or more R8, heterocyclyl optionally substituted by one or more R8, heteroaryl optionally substituted by one or more R6, or aryl optionally substituted by one or more R6;
• each R0 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, carbocyclylalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl, wherein each member of R0 except H is optionally substituted by one or more R*, OR*, N(R*)2, ═O, ═S, halogen, CF3, NO2, CN, —C(O)R*, —CO2R*, —C(O)-aryl, —C(O)-heteroaryl, —C(O)-aralkyl, —S(O)t-aryl, —S(O)t-heteroaryl, —NR*SO2R*, —NR*C(O)R*, —NR*C(O)N(R*)2, —N(R*)C(S)N(R*)2, —NR*CO2R*, —NR*NR*C(O)R*, —NR*NR*C(O)N(R*)2, —NR*NR*CO2R*, —C(O)C(O)R*, —C(O)CH2C(O)R*, —C(O)N(R*)N(R*)2, —C(O)N(R*)2, —C(O)NR*SO2R*, —OC(O)N(R*)2, —S(O)tR*, —NR*SO2N(R*)2, —SO2N(R*)2 wherein the two R*s on the same nitrogen are optionally taken together to form a 5-8 membered saturated, partially saturated or aromatic ring having additional 0-4 heteroatoms selected from oxygen, phosphorus, nitrogen or sulfur;
• and
• each R* is independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heteroaryl.