CERTAIN CYCLOALKYL IMIDAZOPYRIMIDINES, A NEW CLASS OF GABA BRAIN RECEPTOR LIGANDSThis invention encompasses compounds of formula (I) and pharmaceutically acceptable non-toxic salts thereof wherein n is 0, 1, or 2, X is -N=C-R9 or -NR10-C=T, and R1, R2, R3, W and Y are variables. These compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs thereof and are useful in the diagnosis and treatment of anxiety, sleep, and seizure disorders, overdose with benzodiazepine type drugs, and enhancement of alertness.A compound of the formula:and pharmaceutically acceptable non-toxic salts thereof wherein: n is 0, 1 or 2;Ri , R2, and R3 are the same or different and represent hydrogen or straight chain or branched lower alkyl having 1-6 carbon atoms;W is phenyl, thienyl, oxazolyl, 1 ,3,4-oxadiazolyl or pyridyl; orphenyl, thienyl, oxazolyl, 1 ,3,4-oxadiazolyl or pyridyl, each of which is mono or disubstituted with halogen, hydroxy, amino, mono or dialkylamino, straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy having 1-6 carbon atoms;Y is-OR4, -COR4, -CO2R4, -OCOR4, or R4, where R4 is hydrogen, phenyl, thienyl, straight or branched chain lower alkyl having 1-6 carbon atoms, phenylalkyl or thienylalkyl where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;- C ON R4Rδ or -(CH2)n R4R 5 where n=0, 1 , or 2, R4 is hydrogen, phenyl, thienyl, straight or branched chain lower alkyl having 1-6 carbon atoms, phenylalkyl or thienylalkyl where each - 56 - alkyl portion is straight or branched chain lower alkyl having 1- 6 carbon atoms, and R5 is hydrogen or straight or branched chain lower alkyl having 1-6 carbon atoms;5 -CONR4R5 or -(CH2)nNR4Rδ where n=0, 1, or 2, and NR4R5 isN-alkyl-piperazyl, -morpholyl, -piperidyl, or -pyrrolidyl where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;1 0 NR4CO2R6 where R4 is hydrogen, phenyl, thienyl, straight or branched chain lower alkyl having 1-6 carbon atoms, phenylalkyl or thienylalkyl where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms, and RQ is phenyl or straight or branched chain lower alkyl having 1 to 6 carbon1 5 atoms; or-C(OH)R7Rβ where R7 and Rs are the same or different and represent straight or branched chain lower alkyl having 1 to 6 carbon atoms, phenyl or phenylalkyl where each alkyl portion is 20 straight or branched chain lower alkyl having 1-6 carbon atoms;X is -N=C-Rg or -NRι o-C=T,25 with the proviso that when X is -NR1 oC=T, T is oxygen or sulfur and R10 is hydrogen, straight or branched chain lower alkyl containing 1-6 carbon atoms; or3 0 C O R 1 1 where R1 1 is hydrogen, amino, straight or branched chain lower alkyl having 1 -6 carbon atoms, alkoxy having 1-6 carbon atoms, or dialkylamino where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms; and35I when X is -N=C-Rg, R9 is - 57 -hydrogen, halogen, cyano, aryioxy, or alkoxy having 1 -6 carbon atoms, amino, phenylamino, mono- or dialkylamino where each alkyl portion is straight or branched chain alkyl having 1-6 carbon atoms, phenylalkyl amino where 5 the alkyl portion is a straight or branched chain lower alkyl having 1-6 carbon atoms;CORii where Ri 1 is hydrogen, amino, straight or branched chain lower alkyl having 1 -6 carbon atoms,1 0 alkoxy having 1-6 carbon atoms, or dialkylamino where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms; orCONHR12 where R12 is hydrogen or straight or branched 1 5 chain lower alkyl having 1 to 6 carbon atoms. -58- A compound according to Claim 1 of the formula:and pharmaceutically acceptable non-toxic salts thereof wherein:W is phenyl, thienyl, oxazolyl, 1 ,3,4-oxadiazolyl or pyridyl; or1 0 phenyl, thienyl, oxazolyl, 1 ,3,4-oxadiazolyl or pyridyl, each of which is mono or disubstituted with halogen, hydroxy, amino, mono or dialkylamino, straight or branched chain lower alkyl having 1 -6 carbon atoms, or straight or branched chain lower 1 5 alkoxy having 1-6 carbon atoms;Y is-OR4, -COR4, -CO2R4. -OCOR4. or R4, where R4 is hydrogen, phenyl, thienyl, straight or branched chain lower alkyl having 1 -20 6 carbon atoms, phenylalkyl or thienylalkyl where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;- CON R4R5 or -(CH2)nN R4R5 where n=0, 1 , or 2, R4 is 25 hydrogen, phenyl, thienyl, straight or branched chain lower alkyl having 1-6 carbon atoms, phenylalkyl or thienylalkyl where each alkyl portion is straight or branched chain lower alkyl having 1- 6 carbon atoms, and R5 is hydrogen or straight or branched chain lower alkyl having 1-6 carbon atoms;30-CONR4R5 or -(CH2)nNR4R5 where n=0, 1 , or 2, and NR4R5 is N-alkyl-piperazyl, -morpholyl, -piperidyl, or -pyrrolidyl where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;NR4CO2R6 where R4 is hydrogen, phenyl, thienyl, straight or branched chain lower alkyl having 1-6 carbon atoms, phenylalkyl or thienylalkyl where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms, and Re is phenyl or straight or branched chain lower alkyl having 1 to 6 carbon atoms; or-C(OH)R7R8 where R7 and Re are the same or different and represent straight or branched chain lower alkyl having 1 to 6 carbon atoms, phenyl or phenylalkyl where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms; ...
신규부류의 GABA(γ-아미노낙산)브레인 수용기 리간드로서의 특정 싸이클로 알킬 이미다조피리미딘본원은 하기식 화합물 및 그의 제약적으로 용인할만한 비독성 염들에 관한다.〔식중 : n은 0, 1 또는 2이고, X는 -N=C-R9 또는 -NR10-C=T이며, R1, R 2, R3, W 및 Y는 변수임.상기 화합물들은 GABAa 브레인 수용기들 또는 그의 프로드러그들에 대한 고도의 선택적 아고니스트, 길항체 또는 역 아고니스트들이며 불안, 발작질환들과 벤조디 아제핀형타입 약물과용의 진단 및 치료와 주의력 증진에 유용한 것이다.하기식의 화합물 및 그의 제약적으로 용인할 수 있는 비독성염들.  〔식중 : n은 0, 1, 또는 2; R1, R2 및 R3는 서로 같거나 다르고 수소 또는 C1-6 저알킬의 직쇄 또는 분지쇄로 표시되고: W는 페닐, 티에닐, 옥사졸릴, 1, 3, 4-옥사디아졸릴 또는 피리딜; 또는 직각이 할로겐, 하이드록시, 아미노, 모노 또는 다알킬 아미노, 직쇄 또는 분지쇄의 C1-6 저알킬 또는 직쇄 또는 분지쇄의 C1-6 저알콕시로 1 또는 2치환된 페닐, 티에닐, 옥사졸릴, 1, 3, 4-옥사디아졸릴 또는 피리딜 Y는 -OR4, -COR4, -CO2R4, -OCOR4 또는 R4(R4는 수소, 페닐, 티에닐, (각 알킬부분이 직쇄 또는 분지쇄의 C1-6-저알킬인)직쇄 또는 분지쇄의 C1-6저알킬, 페닐알킬 또는 티에닐알킬인); -CONR4R5 또는 -(CH2)nNR4R5(n은 0, 1 또는 2이고 R4는 수소, 페닐, 티에닐, (각 알킬부분이 직쇄 또는 분지쇄의 C1-6-저알킬인)직쇄 또는 분지쇄의 C1-6 저알킬, 페닐알킬 또는티에닐알킬이며 R5는 수소, 또는 직쇄 또는 분지쇄의 C1-6 저알킬인); -CONR4R5 또는 -(CH2)nNR4R5(n은 0, 1 또는 2이고 NR4R5는 (각 알킬부분이 직쇄 또는 분지쇄의 C1-6-저알킬인) N-알킬-피페라질, N-알킬-모르폴릴, N-알킬-피페리딜, 또는 N-알킬-피롤리디인); NR4CO2R5(R4는 수소, 페닐, 티에닐, (각 알킬부분이 직쇄 또는 분지쇄의 C1-6-저알킬); 또는 -C(OH)R7R8(R7 및 R 8은 서로 같거나 다르고 직쇄 또는분지쇄의 C1-6 저알킬); 또는 -C(OH)R7R8(R7 및 R8은 서로 같거나 다르고 직쇄 또는 분지쇄의 C1-6 저알킬, 페닐 또는 페닐알킬(각 알킬부분이 직쇄 또는 분지쇄의 C1-6(저알킬인)인) : X는  또는  단, X가 -NR10C=T일때, T는 수소 또는 황이고 R10은 수소, 직쇄 또는 분지쇄의 C1-6저알킬; 또는 COR11(R11은 수소, 아미노, 직쇄 또는 분지쇄의 C1-6 저알킬, C1-6 알콕시 또는 디알킬아미노(각 알킬부분이 직쇄 또는 분지쇄의 C1-6-저알키린인); 및 X가 일때, R9는 수소, 할로겐, 시아노, 아릴옥시 또는 C1-6 알콕시, 아미노, 페니라미노, 모노-또는 디알킬아미노(가 알킬부분이 직쇄 또는 분지쇄의 C1-6 알킬인), 페닐알킬아미노(알킬부분이 직쇄 또는 분지쇄의 C1-6 저알킬인); COR11(R11은 수소, 아미노, 직쇄 또는 분지쇄 C1-6 저알킬 또는 디알킬아미노(각 알킬부분이 직쇄 또는 분지쇄의 C1-6 저알킬인)인; 또는 CONHR12(R12는 수소 또는, 직쇄 분지쇄의 C1-6 저알킬인)일 것을 조건으로 함.〕