COMPOUNDS AND COMPOSITIONS AS TOLL-LIKE RECEPTOR 7 AGONISTSThe invention provides compounds of formula (I), immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat diseases or disorders associated with Toll-Like Receptor 7 activity.A compound of Formula (I), or pharmaceutically acceptable salt thereof:Formula (I)wherein:R1 is -NHR6 or -NHCHR6R9;R3 is H, -L2C(=0)OR7, -C(=0)OL6R12, -C(=0)OL2R12, -L2C(=0)OL2R12, -L4C(=0)OL5OH, - L4R12, -L2C(=0)OL4C(=0)L2R12, -L2C(=0)OL6R12, -L2C(=0)OL4C(=0)OL2R12, - L2C(=0)OL4C(=0)R12, -L4C(=0)OL2C(=0)R12, -CF2C(=0)R7, - CH=CHC(=0)OL4C(=0)R12, -OL2C(=0)OL4C(=0)R12, -OL4C(=0)OL2R12, - OL4C(=0)OL2C(=0)R12 or -L2C(=0)OL3R12;R4 is H, -L2C(=0)OR7, -C(=0)OL6R12, -C(=0)OL2R12, -L2C(=0)OL2R12, -L4C(=0)OL5OH, - L4R12, -L2C(=0)OL4C(=0)L2R12, -L2C(=0)OL6R12, -L2C(=0)OL4C(=0)OL2R12, - L2C(=0)OL4C(=0)R12, -L4C(=0)OL2C(=0)R12, -CF2C(=0)R7, - CH=CHC(=0)OL4C(=0)R12, -OL2C(=0)OL4C(=0)R12, -OL4C(=0)OL2R12, - OL4C(=0)OL2C(=0)R12 or -L2C(=0)OL3R12;where when R4 is H, then R3 is -L2C(=0)OR7, -C(=0)OL6R12, -C(=0)OL2R12, - L2C(=0)OL2R12, -L4C(=0)OL5OH, -L4R12, - L2C(=0)OL4C(=0)L2R12, -L2C(=0)OL6R12, - L2C(=0)OL4C(=0)OL2R12, -L2C(=0)OL4C(=0)R12, - L4C(=0)OL2C(=0)R12, -CF2C(=0)R7, -CF2C(=0)OR7, - C(=0)OR7, -N(R11)2, -CH=CHC(=0)OL4C(=0)R12, - OL2C(=0)OL4C(=0)R12, -OL4C(=0)OL2R12, - OL4C(=0)OL2C(=0)R12 or -L2C(=0)OL3R12;or when R3 is H, then R4 is -L2C(=0)OR7, -C(=0)OL6R12, -C(=0)OL2R12, - L2C(=0)OL2R12, -L4C(=0)OL5OH, -L4R12, - L2C(=0)OL4C(=0)L2R12, -L2C(=0)OL6R12, - L2C(=0)OL4C(=0)OL2R12, -L2C(=0)OL4C(=0)R12, - L4C(=0)OL2C(=0)R12, -CF2C(=0)R7, -CF2C(=0)OR7, -C(=0)OR7, -N(R11)2, -CH=CHC(=0)OL4C(=0)R12, -OL2C(=0)OL4C(=0)R12, - OL4C(=0)OL2R12, -OL4C(=0)OL2C(=0)R12 or -L2C(=0)OL3R12; l_, is -(CH2)m-;L2 is -(CH2)m-;L3 is -(CH2)m-;L4 is -(CH2)m-;L5 is -(CH2)m-;L6 is -(CH2)mO(CH2)m-;is -(CH2)m-;R6 is -C4-C6alkyl;R7 is -Ci-C3alkyl;R9 is O ;each R11 is independently selected from H or -d-C3alkyl;R12 isf) -N(R11)2;g) an unsubstituted 5-6 membered heterocycloalkyi having 1 to 2 heteroatoms independently selected from N and O;h) a 5-6 membered heterocycloalkyi having 1 to 2 heteroatoms independently selected from N and O substituted with =0;i) a 5-6 membered heterocycloalkyi having 1 to 2 heteroatoms independently selected from N and O substituted with d-C3alkyl or -C(=0)OR7; orj) an unsubstituted phenyl;andeach m is independently selected from 1 , 2, 3, and 4.
톨-유사 수용체 7 효능제로서의 화합물 및 조성물본 발명은 화학식 I의 화합물, 이러한 화합물을 포함하는 면역원성 조성물 및 제약 조성물 및 이러한 화합물을 사용하여 톨-유사 수용체 7 활성과 연관된 질환 또는 장애를 치료하는 방법을 제공한다. <화학식 I>화학식 I의 화합물, 또는 그의 제약상 허용되는 염.<화학식 I>여기서:R1은 -NHR6 또는 -NHCHR6R9이고;R3은 H, -L2C(=O)OR7, -C(=O)OL6R12, -C(=O)OL2R12, -L2C(=O)OL2R12, -L4C(=O)OL5OH, -L4R12, -L2C(=O)OL4C(=O)L2R12, -L2C(=O)OL6R12, -L2C(=O)OL4C(=O)OL2R12, -L2C(=O)OL4C(=O)R12, -L4C(=O)OL2C(=O)R12, -CF2C(=O)R7, -CH=CHC(=O)OL4C(=O)R12, -OL2C(=O)OL4C(=O)R12, -OL4C(=O)OL2R12, -OL4C(=O)OL2C(=O)R12 또는 -L2C(=O)OL3R12이고;R4는 H, -L2C(=O)OR7, -C(=O)OL6R12, -C(=O)OL2R12, -L2C(=O)OL2R12, -L4C(=O)OL5OH, -L4R12, -L2C(=O)OL4C(=O)L2R12, -L2C(=O)OL6R12, -L2C(=O)OL4C(=O)OL2R12, -L2C(=O)OL4C(=O)R12, -L4C(=O)OL2C(=O)R12, -CF2C(=O)R7, -CH=CHC(=O)OL4C(=O)R12, -OL2C(=O)OL4C(=O)R12, -OL4C(=O)OL2R12, -OL4C(=O)OL2C(=O)R12 또는 -L2C(=O)OL3R12이고;여기서 R4가 H인 경우에, R3은 -L2C(=O)OR7, -C(=O)OL6R12, -C(=O)OL2R12, -L2C(=O)OL2R12, -L4C(=O)OL5OH, -L4R12, -L2C(=O)OL4C(=O)L2R12, -L2C(=O)OL6R12, -L2C(=O)OL4C(=O)OL2R12, -L2C(=O)OL4C(=O)R12, -L4C(=O)OL2C(=O)R12, -CF2C(=O)R7, -CF2C(=O)OR7, -C(=O)OR7, -N(R11)2, -CH=CHC(=O)OL4C(=O)R12, -OL2C(=O)OL4C(=O)R12, -OL4C(=O)OL2R12, -OL4C(=O)OL2C(=O)R12 또는 -L2C(=O)OL3R12이거나;또는 R3이 H인 경우에, R4는 -L2C(=O)OR7, -C(=O)OL6R12, -C(=O)OL2R12, -L2C(=O)OL2R12, -L4C(=O)OL5OH, -L4R12, -L2C(=O)OL4C(=O)L2R12, -L2C(=O)OL6R12, -L2C(=O)OL4C(=O)OL2R12, -L2C(=O)OL4C(=O)R12, -L4C(=O)OL2C(=O)R12, -CF2C(=O)R7, -CF2C(=O)OR7, -C(=O)OR7, -N(R11)2, -CH=CHC(=O)OL4C(=O)R12, -OL2C(=O)OL4C(=O)R12, -OL4C(=O)OL2R12, -OL4C(=O)OL2C(=O)R12 또는 -L2C(=O)OL3R12이고;L1은 -(CH2)m-이고;L2는 -(CH2)m-이고;L3은 -(CH2)m-이고;L4는 -(CH2)m-이고;L5는 -(CH2)m-이고;L6은 -(CH2)mO(CH2)m-이고;L9는 -(CH2)m-이고;R6은 -C4-C6알킬이고;R7은 -C1-C3알킬이고;R9는 L1OH이고;각각의 R11은 독립적으로 H 또는 -C1-C3알킬로부터 선택되고;R12는f) -N(R11)2;g) N 및 O로부터 독립적으로 선택된 1 내지 2개의 헤테로원자를 갖는 비치환된 5-6원 헤테로시클로알킬;h) =O로 치환된, N 및 O로부터 독립적으로 선택된 1 내지 2개의 헤테로원자를 갖는 5-6원 헤테로시클로알킬;i) C1-C3알킬 또는 -C(=O)OR7로 치환된, N 및 O로부터 독립적으로 선택된 1 내지 2개의 헤테로원자를 갖는 5-6원 헤테로시클로알킬;또는j) 비치환된 페닐이고;각각의 m은 독립적으로 1, 2, 3, 및 4로부터 선택된다.