NAMPT INHIBITORSDisclosed are compounds which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed.A compound of Fo eutically acceptable salt thereof, Formula (IB)whereinX is N or CY1;Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, CI, Br, and I;R1 is independently selected from the group consisting of NHC(0)NHR3,NHC(0)NH(CH2)mR3x, CH2NHC(0)NHR3, NHC(0)R3, NHC(0)(CH2)nR3,C(0)NH(CH2)nR3, NHC(0)(CH2)mR3x, C(0)NH(CH2)mR3x, CH2C(0)NHR3, andCH2NHC(0)R3; andZ is CH, C-F, C-Cl, C-Br, C-I or N; orX is N or CY1;Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, CI, Br, and I;R1 is hydrogen, F, CI, Br, or I;Z is CR2; andR2 is independently selected from the group consisting of NHC(0)NHR3,NHC(0)NH(CH2)mR3x, CH2NHC(0)NHR3, NHC(0)R3, NHC(0)(CH2)nR3,C(0)NH(CH2)nR3, NHC(0)(CH2)mR3x, C(0)NH(CH2)mR3x, CH2C(0)NHR3, andCH2NHC(0)R3; andR3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(0)R4, S02R4, C(0)R4, CO(0)R4, OC(0)R4, OC(0)OR4, NH2, NHR4, N(R4)2, NHC(0)R4, NR4C(0)R4, NHS(0)2R4, NR4S(0)2R4, NHC(0)OR4, NR4C(0)OR4, NHC(0)NH2, NHC(0)NHR4, NHC(0)N(R4)2, NR4C(0)NHR4, NR4C(0)N(R4)2, C(0)NH2, C(0)NHR4, C(0)N(R4)2, C(0)NHOH,C(0)NHOR4, C(0)NHS02R4, C(0)NR4S02R4, S02NH2, S02NHR4, S02N(R4)2, C(0)H, C(0)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, N02, F, CI, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(0)H, C(0)OH, C(N)NH2, OH, CN, N3, N02, F, CI, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(0)R4, S02R4, C(0)R4, CO(0)R4, OC(0)R4, OC(0)OR4, NH2, NHR4, N(R4)2, NHC(0)R4, NR4C(0)R4, NHS(0)2R4, NR4S(0)2R4, NHC(0)OR4, NR4C(0)OR4, NHC(0)NH2, NHC(0)NHR4, NHC(0)N(R4)2, NR4C(0)NHR4, NR4C(0)N(R4)2, C(0)NH2, C(0)NHR4, C(0)N(R4)2, C(0)NHOH,C(0)NHOR4, C(0)NHS02R4, C(0)NR4S02R4, S02NH2, S02NHR4, S02N(R4)2, C(0)H, C(0)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, N02, F, CI, Br and I;R3x is independently selected from the group consisting of phenyl and heterocyclyl; wherein each R3x phenyl and heterocyclyl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(0)R4, S02R4, C(0)R4, CO(0)R4, OC(0)R4, OC(0)OR4, NH2, NHR4, N(R4)2, NHC(0)R4, NR4C(0)R4, NHS(0)2R4, NR4S(0)2R4, NHC(0)OR4, NR4C(0)OR4, NHC(0)NH2,NHC(0)NHR4, NHC(0)N(R4)2, NR4C(0)NHR4, NR4C(0)N(R4)2, C(0)NH2, C(0)NHR4, C(0)N(R4)2, C(0)NHOH, C(0)NHOR4, C(0)NHS02R4, C(0)NR4S02R4, S02NH2, S02NHR4, S02N(R4)2, C(0)H, C(0)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, N02, F, CI, Br and I;R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2,NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, N02, F, CI, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, C(0)C(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6,NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, N02, F, CI, Br and I; R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(0)R7, S02R7, C(0)R7, CO(0)R7, OC(0)R7, OC(0)OR7, NH2, NHR7, N(R7)2, NHC(0)R7, NR7C(0)R7, NHS(0)2R7, NR7S(0)2R7, NHC(0)OR7, NR7C(0)OR7, NHC(0)NH2, NHC(0)NHR7, NHC(0)N(R7)2, NR7C(0)NHR7, NR7C(0)N(R7)2, C(0)NH2, C(0)NHR7, C(0)N(R7)2, C(0)NHOH,C(0)NHOR7, C(0)NHS02R7, C(0)NR7S02R7, S02NH2, S02NHR7, S02N(R7)2, C(0)H, C(0)OH, C(N)NH...
NAMPT 억제제본 발명은, NAMPT의 활성을 억제하는 화합물들, 상기 화합물들을 포함하는 조성물들 및 질환이 계속되는 동안 NAMPT가 발현되는 질환을 치료하는 방법들을 기재하고 있다.화학식 IB의 화합물, 또는 이의 치료학적으로 허용되는 염. 화학식 IB상기 화학식 IB에서, X는 N 또는 CY1이고;Y1은 수소, 알킬, 알콕시, 할로알킬, 하이드록시알킬, OH, CN, F, Cl, Br, 및 I로 이루어진 그룹으로부터 독립적으로 선택되고;R1은 NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, 및 CH2NHC(O)R3으로 이루어진 그룹으로부터 독립적으로 선택되고; Z는 CH, C-F, C-Cl, C-Br, C-I 또는 N이거나; X는 N 또는 CY1이고;Y1은 수소, 알킬, 알콕시, 할로알킬, 하이드록시알킬, OH, CN, F, Cl, Br, 및 I로 이루어진 그룹으로부터 독립적으로 선택되고;R1은 수소, F, Cl, Br, 또는 I이고; Z는 CR2이고;R2는 NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, 및 CH2NHC(O)R3으로 이루어진 그룹으로부터 독립적으로 선택되고; R3은 페닐 및 5 내지 6원 헤테로아릴로 이루어진 그룹으로부터 독립적으로 선택되고; 여기서, 각각의 R3으로서의 페닐은 R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br 및 I로 이루어진 그룹으로부터 독립적으로 선택된 1개의 치환체로 파라 위치에서 치환되고; 여기서, 각각의 R3으로서의 페닐은 알킬, 할로알킬, 알콕시알킬, 하이드록시알킬, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br 및 I로 이루어진 그룹으로부터 독립적으로 선택된 1개의 치환체로 임의로 추가로 치환되고; 여기서, 각각의 R3으로서의 5 내지 6원 헤테로아릴은 R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br 및 I로 이루어진 그룹으로부터 독립적으로 선택된 1, 2, 3 또는 4개의 치환체로 치환되고;R3x는 페닐 및 헤테로사이클릴로 이루어진 그룹으로부터 독립적으로 선택되고; 여기서, 각각의 R3x로서의 페닐 및 헤테로사이클릴은 R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br 및 I로 이루어진 그룹으로부터 독립적으로 선택된 1, 2, 3 또는 4개의 치환체로 치환되고;R4는, 각각의 발생(occurrence)에서, 알킬, 알케닐, 알키닐, 아릴, 사이클로알킬, 사이클로알케닐, 및 3 내지 12원 헤테로사이클릴로 이루어진 그룹으로부터 독립적으로 선택되고; 여기서, 각각의 R4로서의 알킬, 알케닐, 및 알키닐은 R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br 및 I로 이루어진 그룹으로부터 독립적으로 선택된 1, 2, 3 또는 4개의 치환체로 임의로 치환되고; 여기서, 각각의 R4로서의 아릴, 사이클로알킬, 사이클로알케닐, 및 3 내지 12원 헤테로사이클릴은 R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br 및 I로 이루어진 그룹으로부터 독립적으로 선택된 1, 2, 3 또는 4개의 치환체로 임의로 치환되고;R5는, 각각의 발생에서, 알킬, 알케닐, 알키닐, 아릴, 헤테로사이클릴, 사이클로알킬, 및 사이클로알케닐로 이루어진 그룹으로부터 독립적으로 선택되고; 여기서, 각각의 R5로서의 알킬, 알케닐, 및 알키닐은 R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br 및 I로 이루어진 그룹으로부터 독립적으로 선택된 1, 2, 3 또는 4개의 치환체로 임의로 치환되고; 여기서, 각각의 R5로서의 아릴, 사이클로알킬, 사이클로알케닐, 및 헤테로사이클릴은 R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br 및 I로 이루어진 그룹으로부터 독립적으로 선택된 1, 2, 3 또는 4개의 치환체로 임의로 치환되고;R6은, 각각의 발생에서, 알킬, 알케닐, 알키닐, 아릴, 헤테로사이클릴, 사이클로알킬, 및 사이클로알케닐로 이루어진 그룹으로부터 독립적으로 선택되고; 여기서, 각각의 R6으로서의 알킬, 알케닐, 및 알키닐은 R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O...