Diazahomoadamantane derivatives and methods of use thereofThe invention relates to compounds that are diazahomoadamantane derivatives, compositions comprising such compounds, and methods of using such compounds and compositions.The compound of formula (i)whereinx is ch 2or c=o; r is a hydrogen, ar 1, ar 2-ar 3,-(ch 2) qar 3,-c (o) ar 3,-c (o) oar 3,-c (o) nr 1r 2,-c (o)-(cr xr y) q-ar 3,-c (o)-(cr xr y) q-o-ar 3,-c (o)-ar 2-ar 3, or (i); ar 1, ar 2, and ar 3be aryl or heteroaryl independently of one another; a is aryl or heteroaryl;q is 1,2,3,4, or 5;r and s are 0,1,2 or 3 independently, wherein r and s be 2,3 or 4;r 1it is hydrogen or alkyl; r 2be aryl, arylalkyl, heteroaryl, or heteroarylalkyl; r xand r y, when occurring each time, be hydrogen independently of one another, alkyl, fluorine, or haloalkyl; wherein each aryl or heteroaryl or the aryl on arylalkyl and heteroarylalkyl group and heteroaryl moieties are unsubstituted or to be selected from following substituting group by 1,2,3,4 or 5 substituted: alkyl, thiazolinyl, alkynyl, halogen, cyanic acid ,-g independently 1,-no 2,-or 1a,-o-(cr 4ar 5a) p-o-,-oc (o) r 1a,-oc (o) n (r b) (r 3a) ,-sr 1a,-s (o) 2r 2a,-s (o) 2n (r b) (r 3a) ,-c (o) r 1a,-c (o) or 1a,-c (o) n (r b) (r 3a) ,-n (r b) (r 3a) ,-n (r a) c (o) r 1a,-n (r a) c (o) o (r 1a) ,-n (r a) c (o) n (r b) (r 3a) ,-(cr 4ar 5a) m-no 2,-(cr 4ar 5a) m-or 1a,-(cr 4ar 5a) m-oc (o) r 1a,-(cr 4ar 5a) m-oc (o) n (r b) (r 3a) ,-(cr 4ar 5a) m-sr 1a,-(cr 4ar 5a) m-s (o) 2r 2a,-(cr 4ar 5a) m-s (o) 2n (r b) (r 3a) ,-(cr 4ar 5a) m-c (o) r 1a,-(cr 4ar 5a) m-c (o) or 1a,-(cr 4ar 5a) m-c (o) n (r b) (r 3a) ,-(cr 4ar 5a) m-n (r b) (r 3a) ,-(cr 4ar 5a) m-n (r a) c (o) r 1a,-(cr 4ar 5a) m-n (r a) c (o) o (r 1a) ,-(cr 4ar 5a) m-n (r a) c (o) n (r b) (r 3a) ,-(cr 4ar 5a) m-g 2, cyanic acid alkyl, and haloalkyl; wherein r 1aand r 3a, when occurring each time, be hydrogen independently of one another, alkyl, haloalkyl, g 2, or-(cr 6ar 7a) n-g 2r 2a, when occurring each time, be alkyl independently, haloalkyl, g 2, or-(cr 6ar 7a) n-g 2r 4a, r 5a, r 6a, and r 7a, when occurring each time, be hydrogen independently of one another, halogen, alkyl, or haloalkyl; r aand r b, when occurring each time, be hydrogen independently of one another, alkyl, or haloalkyl; m and n when occurring each time, are 1,2,3,4 independently of one another, or 5;p when occurring each time, is 1 or 2;-o-(cr 4ar 5a) p-o-is the divalent substituent that is connected to two adjacent carbonss of aryl or heteroaryl; g 1, when occurring each time, be heterocycle or naphthenic base, each g wherein 1be unsubstituted independently or to be selected from following substituting group by 1,2,3,4 or 5 substituted: alkyl, thiazolinyl, alkynyl, halogen, cyanic acid, oxo ,-no 2,-or 1b,-oc (o) r 1b,-oc (o) n (r b) (r 3b) ,-sr 1b,-s (o) 2r 2b,-s (o) 2n (r b) (r 3b) ,-c (o) r 1b,-c (o) or 1b,-c (o) n (r b) (r 3b) ,-n (r b) (r 3b) ,-n (r a) c (o) r 1b,-n (r a) c (o) o (r 1b) ,-n (r a) c (o) n (r b) (r 3b) ,-(cr 4br 5b) m-no 2,-(cr 4br 5b) m-or 1b,-(cr 4br 5b) m-oc (o) r 1b,-(cr 4br 5b) m-oc (o) n (r b) (r 3b) ,-(cr 4br 5b) m-sr 1b,-(cr 4br 5b) m-s (o) 2r 2b,-(cr 4br 5b) m-s (o) 2n (r b) (r 3b) ,-(cr 4br 5b) m-c (o) r 1b,-(cr 4br 5b) m-c (o) or 1b,-(cr 4br 5b) m-c (o) n (r b) (r 3b) ,-(cr 4br 5b) m-n (r b) (r 3b) ,-(cr 4br 5b) m-n (r a) c (o) r 1b,-(cr 4br 5b) m-n (r a) c (o) o (r 1b) ,-(cr 4br 5b) m-n (r a) c (o) n (r b) (r 3b), cyanic acid alkyl, and haloalkyl; r 1band r 3b, when occurring each time, be hydrogen independently of one another, alkyl, or haloalkyl; r 2b, when occurring each time, be alkyl or haloalkyl independently; r 4band r 5b, when occurring each time, be hydrogen independently of one another, halogen, alkyl, or haloalkyl; with g 2, when occurring each time, be aryl, heteroaryl, heterocycle, or naphthenic base, wherein each g 2be unsubstituted independently or to be selected from following substituting group by 1,2,3,4 or 5 substituted: alkyl, thiazolinyl, alkynyl, halogen, cyanic acid, oxo ,-no 2,-or 1b,-oc (o) r 1b,-oc (o) n (r b) (r 3b) ,-sr 1b,-s (o) 2r 2b,-s (o) 2n (r b) (r 3b) ,-c (o) r 1b,-c (o) or 1b,-c (o) n (r b) (r 3b) ,-n (r b) (r 3b) ,-n (r a) c (o) r 1b,-n (r a) c (o) o (r 1b) ,-n (r a) c (o) n (r b) (r 3b) ,-(cr 4br 5b) m-no 2,-(cr 4br 5b) m-or 1b,-(cr 4br 5b) m-oc (o) r 1b,-(cr 4br 5b) m-oc (o) n (r b) (r 3b) ,-(cr 4br 5b) m-sr 1b,-(cr 4br 5b) m-s (o) 2r 2b,-(cr 4br 5b) m-s (o) 2n (r b) (r 3b) ,-(cr 4br 5b) m-c (o) r 1b,-(cr 4br 5b) m-c (o) or 1b,-(cr 4br 5b) m-c (o) n (r b) (r 3b) ,-(cr 4br 5b) m-n (r b) (r 3b) ,-(cr 4br 5b) m-n (r a) c (o) r 1b,-(cr 4br 5b) m-n (r a) c (o) o (r 1b) ,-(cr 4br 5b) m-n (r a) c (o) n (r b) (r 3b), cyanic acid alkyl, and haloalkyl; or its acceptable for pharmaceutical salt, acid amides, ester or prodrug.
디아자호모아다만탄 유도체 및 이들의 사용 방법본 발명은 디아자호모아다만탄 유도체인 화합물, 이러한 화합물을 포함하는 조성물, 및 이러한 화합물 및 조성물의 사용 방법에 관한 것이다.화학식 I의 화합물, 또는 이의 약제학적으로 허용되는 염, 아미드, 에스테르 또는 전구약물.화학식 I[이미지]위의 화학식 I에서,X는 CH2 또는 C=O이고;R은 수소, Ar1, Ar2-Ar3, -(CH2)qAr3, -C(O)Ar3, -C(O)OAr3, -C(O)NR1R2, -C(O)-(CRxRy)q-Ar3, -C(O)-(CRxRy)q-O-Ar3, -C(O)-Ar2-Ar3 또는 [이미지](i)이고;Ar1, Ar2 및 Ar3은 각각 독립적으로 아릴 또는 헤테로아릴이고;A는 알릴 또는 헤테로아릴이고;q는 1, 2, 3, 4 또는 5이고;r 및 s는 독립적으로 0, 1, 2 또는 3이고, 여기서, r과 s의 총합은 2, 3 또는 4이고;R1은 수소 또는 알킬이고;R2는 아릴, 아릴알킬, 헤테로아릴 또는 헤테로알릴알킬이고;Rx 및 Ry는, 각각의 경우, 각각 독립적으로 수소, 알킬, 불소 또는 할로알킬이고;여기서, 각각의 아릴 또는 헤테로아릴, 또는 아릴알킬 및 헤테로아릴알킬 그룹 상의 아릴 및 헤테로아릴 잔기(moiety)는 독립적으로 치환되지 않거나 알킬, 알케닐, 알키닐, 할로겐, 시아노, -G1, -NO2, -OR1a, -O-(CR4aR5a)p-O-, -OC(O)R1a, -OC(O)N(Rb)(R3a), -SR1a, -S(O)2R2a, -S(O)2N(Rb)(R3a), -C(O)R1a, -C(O)OR1a, -C(O)N(Rb)(R3a), -N(Rb)(R3a), -N(Ra)C(O)R1a, -N(Ra)C(O)O(R1a), -N(Ra)C(O)N(Rb)(R3a), -(CR4aR5a)m-NO2, -(CR4aR5a)m-OR1a, -(CR4aR5a)m-OC(O)R1a, -(CR4aR5a)m-OC(O)N(Rb)(R3a), -(CR4aR5a)m-SR1a, -(CR4aR5a)m-S(O)2R2a, -(CR4aR5a)m-S(O)2N(Rb)(R3a), -(CR4aR5a)m-C(O)R1a, -(CR4aR5a)m-C(O)OR1a, -(CR4aR5a)m-C(O)N(Rb)(R3a), -(CR4aR5a)m-N(Rb)(R3a), -(CR4aR5a)m-N(Ra)C(O)R1a, -(CR4aR5a)m-N(Ra)C(O)O(R1a), -(CR4aR5a)m-N(Ra)C(O)N(Rb)(R3a), -(CR4aR5a)m-G2, 시아노알킬 및 할로알킬로 이루어진 그룹으로부터 선택되는 1, 2, 3, 4 또는 5개의 치환체로 치환되고; 여기서,R1a 및 R3a는, 각각의 경우, 각각 독립적으로 수소, 알킬, 할로알킬, G2 또는 -(CR6aR7a)n-G2이고;R2a는, 각각의 경우, 독립적으로 알킬, 할로알킬, G2 또는 -(CR6aR7a)n-G2이고;R4a, R5a, R6a 및 R7a는, 각각의 경우, 각각 독립적으로 수소, 할로겐, 알킬 또는 할로알킬이고;Ra 및 Rb는, 각각의 경우, 각각 독립적으로 수소, 알킬 또는 할로알킬이고;m 및 n은, 각각의 경우, 각각 독립적으로 1, 2, 3, 4 또는 5이고;p는, 각각의 경우, 1 또는 2이고;-O-(CR4aR5a)p-O-는 아릴 또는 헤테로아릴의 2개의 인접한 탄소 원자에 결합된 2가 치환체이고;G1은, 각각의 경우, 헤테로사이클 또는 사이클로알킬이고, 여기서, 각각의 G1은 독립적으로 치환되지 않거나 알킬, 알케닐, 알키닐, 할로겐, 시아노, 옥소, -NO2, -OR1b, -OC(O)R1b, -OC(O)N(Rb)(R3b), -SR1b, -S(O)2R2b, -S(O)2N(Rb)(R3b), -C(O)R1b, -C(O)OR1b, -C(O)N(Rb)(R3b), -N(Rb)(R3b), -N(Ra)C(O)R1b, -N(Ra)C(O)O(R1b), -N(Ra)C(O)N(Rb)(R3b), -(CR4bR5b)m-NO2, -(CR4bR5b)m-OR1b, -(CR4bR5b)m-OC(O)R1b, -(CR4bR5b)m-OC(O)N(Rb)(R3b), -(CR4bR5b)m-SR1b, -(CR4bR5b)m-S(O)2R2b, -(CR4bR5b)m-S(O)2N(Rb)(R3b), -(CR4bR5b)m-C(O)R1b, -(CR4bR5b)m-C(O)OR1b, -(CR4bR5b)m-C(O)N(Rb)(R3b), -(CR4bR5b)m-N(Rb)(R3b), -(CR4bR5b)m-N(Ra)C(O)R1b, -(CR4bR5b)m-N(Ra)C(O)O(R1b), -(CR4bR5b)m-N(Ra)C(O)N(Rb)(R3b), 시아노알킬 및 할로알킬로 이루어진 그룹으로부터 선택되는 1, 2, 3, 4 또는 5개의 치환체로 치환되고;R1b 및 R3b는, 각각의 경우, 각각 독립적으로 수소, 알킬 또는 할로알킬이고;R2b는, 각각의 경우, 독립적으로 알킬 또는 할로알킬이고;R4b 및 R5b는, 각각의 경우, 각각 독립적으로 수소, 할로겐, 알킬 또는 할로알킬이고;G2는, 각각의 경우, 아릴, 헤테로아릴, 헤테로사이클 또는 사이클로알킬이고, 여기서, 각각의 G2는 독립적으로 치환되지 않거나 알킬, 알케닐, 알키닐, 할로겐, 시아노, 옥소, -NO2, -OR1b, -OC(O)R1b, -OC(O)N(Rb)(R3b), -SR1b, -S(O)2R2b, -S(O)2N(Rb)(R3b), -C(O)R1b, -C(O)OR1b, -C(O)N(Rb)(R3b), -N(Rb)(R3b), -N(Ra)C(O)R1b, -N(Ra)C(O)O(R1b), -N(Ra)C(O)N(Rb)(R3b), -(CR4bR5b)m-NO2, -(CR4bR5b)m-OR1b, -(CR4bR5b)m-OC(O)R1b, -(CR4bR5b)m-OC(O)N(Rb)(R3b), -(CR4bR5b)m-SR1b, -(CR4bR5b)m-S(O)2R2b, -(CR4bR5b)m-S(O)2N(Rb)(R3b), -(CR4bR5b)m-C(O)R1b, -(CR4bR5b)m-C(O)OR1b, -(CR4bR5b)m-C(O)N(Rb)(R3b), -(CR4bR5b)m-N(Rb)(R3b), -(CR4bR5b)m-N(Ra)C(O)R1b, -(CR4bR5b)m-N(Ra)C(O)O(R1b), -(CR4bR5b)m-N(Ra)C(O)N(Rb)(R3b), 시아노알킬 및 할로알킬로 이루어진 그룹으로부터 선택되는 1, 2, 3, 4 또는 5개의 치환체로 치환된다.