Piperazinyl derivatives as modulators of chemokine receptor activityThe present application describes modulators of MIP-1a of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof, wherein m, T, W, R1, R4, R5, R5a and R5b are as defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis using said modulators are disclosed.The compound of a formula (i):or its steric isomer or prodrug or pharmacy acceptable salt, wherein:t does not exist, or is w is-chr 3a-,-chr 3achr 3b-or cycloalkyl; r 1be alkyl, cycloalkyl, aryl, heterocyclic radical or heteroaryl, it all can be chosen wantonly by 0-5 r 1areplace; r 1abe independently selected from when occurring at every turn alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclic radical, heterocyclic radical alkyl, halogen ,-nh 2,-cn ,-no 2,-c (=o) oh ,-c (=o) o (cr 8r 8) rr 10,-o (cf 2) rcf 3,-o (cr 8r 8) rr 10,-oh ,-sh ,-s (cr 8r 8) rr 10,-s (o) 3h ,-p (o) 3h 2,-c (=o) nr 9r 9,-nr 9r 9,-s (o) 2nr 9r 9,-nr 9s (o) 2(cf 2) rcf 3,-c (=o) nr 9s (o) 2r 6,-s (o) 2nr 9c (=o) or 6,-s (o) 2nr 9c (=o) nr 9r 9,-c (=o) nr 9s (o) 2(cf 2) rcf 3,-c (=o) (cr 8r 8) rr 10,-nr 9c (=o) h ,-nr 9c (=o) (cr 8r 8) rr 10,-oc (=o) (cr 8r 8) rr 10,-c (=nr 14) nr 9r 9,-nhc (=nr 14) nr 14r 14,-s (=o) (cr 8r 8) rr 10,-s (o) 2(cr 8r 8) rr 10,-nr 9c (=o) or 8,-nr 9s (o 2) r 8,-s (o) 2nr 9c (o) r 6, aryloxy or arylalkyl, wherein said aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclic radical, heterocyclic radical alkyl, aryloxy and arylalkyl can be chosen wantonly by 0-3 r 1breplace; r 1bbe independently selected from when occurring at every turn alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclic radical, heterocyclic radical alkyl, halogen ,-nh 2,-cn ,-no 2,-c (=o) oh ,-c (=o) o (cr 8r 8) rr 10,-o (cf 2) rcf 3,-o (cr 8r 8) rr 10,-oh ,-sh ,-s (cr 8r 8) rr 10,-s (o) 3h ,-p (o) 3h 2,-c (=o) nr 9r 9,-nr 9r 9,-s (o) 2nr 9r 9,-nr 9s (o) 2(cf 2) rcf 3,-c (=o) nr 9s (o) 2r 6,-s (o) 2nr 9c (=o) or 6,-s (o) 2nr 9c (=o) nr 9r 9,-c (=o) nr 9s (o) 2(cf 2) rcf 3,-c (=o) (cr 8r 8) rr 10,-nr 9c (=o) h ,-nr 9c (=o) (cr 8r 8) rr 10,-oc (=o) (cr 8r 8) rr 10,-c (=nr 14) nr 9r 9,-nhc (=nr 14) nr 14r 14,-s (=o) (cr 8r 8) rr 10,-s (o) 2(cr 8r 8) rr 10,-nr 9c (=o) or 8,-nr 9s (o 2) r 8, aryloxy or arylalkyl; r 3aand r 3bindependently be hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkylalkyl or arylalkyl when occurring, wherein said alkyl can be replaced by-oh at every turn; r 4when occurring be at every turn f ,-oh or alkyl; or any two the alkyl r4 that link to each other with identical carbon atoms can form 3-unit and encircle the unit ring to 6-, and it is optional can to comprise 1-4 heteroatoms that is selected from n, o and s; r 5for hydrogen, halogen ,-cn or-the o alkyl; r 5afor hydrogen, halogen ,-cn or-the o alkyl; r 5bfor hydrogen, halogen ,-cn or-the o alkyl; condition is r 5, r 5aand r 5bbe not hydrogen entirely; r 6independently be alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl when occurring at every turn; r 8independently be hydrogen or alkyl when occurring at every turn; r 9independently be hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclic radical or heterocyclic radical alkyl when occurring, wherein said aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclic radical or heterocyclic radical alkyl can be chosen wantonly by 0-5 r at every turn 9areplace, and described heteroaryl, heteroarylalkyl, heterocyclic radical or heterocyclic radical alkyl comprise 1-4 heteroatoms that is selected from n, o and s; r 9abe independently selected from when occurring at every turn alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclic radical, heterocyclic radical alkyl, halogen ,-nh 2,-cn ,-no 2,-c (=o) oh ,-c (=o) o (cr 8r 8) rr 14,-o (cf 2) rcf 3,-o (cr 8r 8) rr 14,-oh ,-sh ,-s (cr 8r 8) rr 14,-s (o) 3h ,-p (o) 3h 2,-c (=o) nr 14r 14,-nr 14r 14,-s (o) 2nr 14r 14,-nr 14s (o) 2(cf 2) rcf 3,-c (=o) nr 14s (o) 2r 6,-s (o) 2nr 14c (=o) or 6,-s (o) 2nr 14c (=o) nr 14r 14,-c (=o) nr 14s (o) 2(cf 2) rcf 3,-c (=o) (cr 8r 8) rr 14,-nr 14c (=o) h ,-nr 14c (=o) (cr 8r 8) rr 14,-oc (=o) (cr 8r 8) rr 14,-c (=nr 14) nr 14r 14,-nhc (=nr 14) nr 14r 14,-s (=o) (cr 8r 8) rr 14,-s (o) 2(cr 8r 8) rr 14,-nr 14c (=o) or 8,-nr 14s (o 2) r 8, aryloxy or arylalkyl; r 10be independently selected from alkyl, aryl, arylalkyl, heterocyclic radical or heterocyclic radical alkyl when occurring, wherein said alkyl, aryl, arylalkyl, heterocyclic radical or heterocyclic radical alkyl can be chosen wantonly by 0-3 r at every turn 10areplace, and described heterocyclic radical and heterocyclic radical alkyl comprise 1-4 heteroatoms that is selected from n, o and s; r 10abe independently selected from when occurring at every turn alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclic radical, heterocyclic radical alkyl, halogen ,-nh 2,-cn ,-no 2,-c (=o) oh ,-c (=o) o (cr 8r 8) rr 14,-o (cf 2) rcf 3,-o (cr 8r 8) rr 14,-oh ,-sh ,-s (cr 8r 8) rr 14,-s (o) 3h ,-p (o) 3h 2,-c (=o) nr 14r 14,-nr 14r 14,-s (o) 2nr 14r 14,-nr 14s (o) 2(cf 2) rcf 3,-c...
케모킨 수용체 활성 조절인자로서의 피페라지닐 유도체본 출원은 하기 화학식 I 또는 이의 입체이성질체 또는 제약상 허용되는 염인 MIP-1α 조절인자에 관한 것이다. <화학식 I>  상기 식 중, m, T, W, R1, R4, R5, R5a 및 R5b는 본원에 정의된 바와 같다. 또한, 상기 조절인자를 사용하는 염증성 질환, 예컨대 천식 및 알레르기성 질환, 뿐만 아니라 자가면역 병리, 예컨대 류마티스성 관절염 및 아테롬성동맥경화증의 치료 및 예방 방법이 개시되어 있다.하기 화학식 I의 화합물, 또는 이의 입체이성질체, 전구약물 또는 제약상 허용되는 염. <화학식 I> [이미지] 상기 식 중, T는 존재하지 않거나, [이미지]이고; W는 -CHR3a-, -CHR3aCHR3b- 또는 시클로알킬이고; R1은 알킬, 시클로알킬, 아릴, 헤테로시클릴 또는 헤테로아릴이고, 이들 모두는 0 내지 5개의 R1a로 임의로 치환될 수 있고; R1a는, 각각의 경우에, 독립적으로 알킬, 할로알킬, 아릴, 알케닐, 알키닐, 시클로알킬, 시클로알킬알킬, 헤테로아릴, 헤테로아릴알킬, 헤테로시클릴, 헤테로시클릴알킬, 할로, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)O(CR8R8)rR10, -O(CF2)rCF3, -O(CR8R8)rR10, -OH, -SH, -S(CR8R8)rR10, -S(O)3H, -P(O)3H2, -C(=O)NR9R9, -NR9R9, -S(O)2NR9R9, -NR9S(O)2(CF2)rCF3, -C(=O)NR9S(O)2R6, -S(O)2NR9C(=O)OR6, -S(O)2NR9C(=O)NR9R9, -C(=O)NR9S(O)2(CF2)rCF3, -C(=O)(CR8R8)rR10, -NR9C(=O)H, -NR9C(=O)(CR8R8)rR10, -OC(=O)(CR8R8)rR10, -C(=NR14)NR9R9, -NHC(=NR14)NR14R14, -S(=O)(CR8R8)rR10, -S(O)2(CR8R8)rR10, -NR9C(=O)OR8, -NR9S(O2)R8, -S(O)2NR9C(O)R6, 아릴옥시 또는 아릴알킬로부터 선택되고, 이때 상기 아릴, 시클로알킬, 시클로알킬알킬, 헤테로아릴, 헤테로아릴알킬, 헤테로시클릴, 헤테로시클릴알킬, 아릴옥시 및 아릴알킬은 0 내지 3개의 R1b로 임의로 치환될 수 있고; R1b는, 각각의 경우에, 독립적으로 알킬, 할로알킬, 아릴, 알케닐, 알키닐, 시클로알킬, 시클로알킬알킬, 헤테로아릴, 헤테로아릴알킬, 헤테로시클릴, 헤테로시클릴알킬, 할로, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)O(CR8R8)rR10, -O(CF2)rCF3, -O(CR8R8)rR10, -OH, -SH, -S(CR8R8)rR10, -S(O)3H, -P(O)3H2, -C(=O)NR9R9, -NR9R9, -S(O)2NR9R9, -NR9S(O)2(CF2)rCF3, -C(=O)NR9S(O)2R6, -S(O)2NR9C(=O)OR6, -S(O)2NR9C(=O)NR9R9, -C(=O)NR9S(O)2(CF2)rCF3, -C(=O)(CR8R8)rR10, -NR9C(=O)H, -NR9C(=O)(CR8R8)rR10, -OC(=O)(CR8R8)rR10, -C(=NR14)NR9R9, -NHC(=NR14)NR14R14, -S(=O)(CR8R8)rR10, -S(O)2(CR8R8)rR10, -NR9C(=O)OR8, -NR9S(O2)R8, 아릴옥시 또는 아릴알킬로부터 선택되고; R3a 및 R3b는, 각각의 경우에, 독립적으로 수소, 알킬, 시클로알킬, 알케닐, 시클로알킬알킬 또는 아릴알킬이고, 이때 상기 알킬은 -OH로 치환될 수 있고; R4는, 각각의 경우에, F, -OH 또는 알킬이거나; 또는 동일한 탄소 원자에 부착된 임의의 2개의 알킬인 R4는 N, O 및 S로부터 선택된 1 내지 4개의 헤테로원자를 임의로 함유할 수 있는 3- 내지 6-원의 고리를 형성할 수 있고; R5는 수소, 할로, -CN 또는 -O알킬이고; R5a는 수소, 할로, -CN 또는 -O알킬이고; R5b는 수소, 할로, -CN 또는 -O알킬이되; 단, R5, R5a 및 R5b가 모두 수소는 아니고; R6은, 각각의 경우에, 독립적으로 알킬, 시클로알킬, 시클로알킬알킬, 아릴, 아릴알킬, 헤테로아릴 또는 헤테로아릴알킬이고; R8은, 각각의 경우에, 독립적으로 수소 또는 알킬이고; R9는, 각각의 경우에, 독립적으로 수소, 알킬, 시클로알킬, 아릴, 아릴알킬, 헤테로아릴, 헤테로아릴알킬, 헤테로시클릴 또는 헤테로시클릴알킬이고, 이때 상기 아릴, 아릴알킬, 헤테로아릴, 헤테로아릴알킬, 헤테로시클릴 또는 헤테로시클릴알킬은 0 내지 5개의 R9a로 임의로 치환될 수 있고, 상기 헤테로아릴, 헤테로아릴알킬, 헤테로시클릴 또는 헤테로시클릴알킬은 N, O 및 S로부터 선택된 1 내지 4개의 헤테로원자를 함유하고; R9a는, 각각의 경우에, 독립적으로 알킬, 할로알킬, 아릴, 알케닐, 알키닐, 시클로알킬, 시클로알킬알킬, 헤테로아릴, 헤테로아릴알킬, 헤테로시클릴, 헤테로시클릴알킬, 할로, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)O(CR8R8)rR14, -O(CF2)rCF3, -O(CR8R8)rR14, -OH, -SH, -S(CR8R8)rR14, -S(O)3H, -P(O)3H2, -C(=O)NR14R14, -NR14R14, -S(O)2NR14R14, -NR14S(O)2(CF2)rCF3, C(=O)NR14S(O)2R6, -S(O)2NR14C(=O)OR6, -S(O)2NR14C(=O)NR14R14, -C(=O)NR14S(O)2(CF2)rCF3, -C(=O)(CR8R8)rR14, -NR14C(=O)H, -NR14C(=O)(CR8R8)rR14, -OC(=O)(CR8R8)rR14, -C(=NR14)NR14R14, -NHC(=NR14)NR14R14, -S(=O)(CR8R8)rR14, -S(O)2(CR8R8)rR14, -NR14C(=O)OR8, -NR14S(O2)R8, 아릴옥시 또는 아릴알킬로부터 선택되고; R10은, 각각의 경우에, 독립적으로 알킬, 아릴, 아릴알킬, 헤테로시클릴 또는 헤테로시클릴알킬로부터 선택되고, 이때 상기 알킬, 아릴, 아릴알킬, 헤테로시클릴 또는 헤테로시클릴알킬은 0 내지 3개의 R10a로 임의로 치환될 수 있고, 상기 헤테로시클릴 및 헤테로시클릴알킬은 N, O 및 S로부터 선택된 1 내지 4개의 헤테로원자를 함유하고; R10a는, 각각의 경우에, 독립적으로 알킬, 할로알킬, 아릴, 알케닐, 알키닐, 시클로알킬, 시클로알킬알킬, 헤테로아릴, 헤테로아릴알킬, 헤테로시클릴, 헤테로시클릴알킬, 할로, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)O(CR8R8)rR14, -O(CF2)rCF3, -O(CR8R8)rR14, -OH, -SH, -S(CR8R8)rR14, -S(O)3H, -P(O)3H2, -C(=O)NR14R14, -NR14R14, -S(O)2NR14R14, -NR14S(O)2(CF2)rCF3, -C(=O)NR14S(O)2R6, -S(O)2NR14C(=O)OR6, -S(O)2NR14C(=O)NR14R14, -C(=O)NR14S(O)2(CF2)rCF3, -C(=O)(CR8R8)rR14, -NR14C(=O)H, -NR14C(=O)(CR8R8)rR14, -OC(=O)(CR8R8)rR14, -C(=NR14)NR14R14, -NHC(=NR14)NR14R14, -S(=O)(CR8R8)rR14, -S(O)2(CR8R8)rR14, -NR14C(=O)OR8, -NR14S(O2)R8, 아릴옥시 또는 아릴알킬로부터 선택되고; R14는, 각각의 경우에, 독립적으로 수소, 알킬, 시클로알킬 또는 페닐로부터 선택되고; m은 0 내지 2이고; r은 0 내지 5이되; 단, 하기 구조의 화합물은 제외한다. [이미지]