Novel azabenzimidazole hexahydrofuro[3,2-b]furan derivativesNovel compounds of the structural formula (I) are activators of AMP-protein kinase and may be useful in the treatment, prevention and suppression of diseases mediated by the AMPK activated protein kinase. The compounds of the present invention may be useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.The compound of structural formula i:or its officinal salt, wherein:t is selected from: cr 3, n and n-oxide; u is selected from: cr 1, n and n-oxide; v is selected from: cr 2, n and n-oxide; w is selected from: cr 4, n and n-oxide, condition is at least one in t, u, v and w is n or n-oxide;x is selected from:(1) -ch 2-， (2) -chf-，(3) -cf 2-， (4) -s-，(5) -o-，(6) –o-ch 2-， (7) –o-ch 2ch 2-， (8) -nh-，(9) -c(o)-，(10) -nhc(o)-，(11) -c(o)nh-，(12) -nhso 2-， (13)-so 2nh-, and (14) -co 2-， wherein each ch 2be unsubstituted or be selected from following substituent group by 1 or 2 and replace: hydroxyl, halogen, nh 2, c 1-6alkyl, co 2h, co 2c 1-6alkyl, coc 1-6alkyl, phenyl and-ch 2phenyl, and wherein each nh is unsubstituted or is selected from following substituent group by 1 and replaces: c 1-6alkyl, co 2h, co 2c 1-6alkyl, coc 1-6alkyl, phenyl and-ch 2phenyl; y is selected from:wherein a is selected from: ch 2, nh, nc 1-6alkyl, o and s, and wherein y is unsubstituted or is selected from r by 1,2,3 or 4 bsubstituent group replace; z is selected from:(1) nr 5， (2)-s-, and(3) -o-；each r 1and r 2independently selected from: (1) hydrogen,(2) halogen,(3) cn，(4) cf 3， (5)-c 1-6alkyl, (6)-c 2-6thiazolinyl, (7)-c 2-6alkynyl, (8)-(ch 2) pc 3-10cycloalkyl, (9)-(ch 2) pc 3-7cycloalkyl-aryl groups, (10)-(ch 2) pc 3-7cycloalkyl-heteroaryl, (11)-(ch 2) pc 4-10cycloalkenyl group, (12)-(ch 2) pc 4-7cycloalkenyl group-aryl, (13)-(ch 2) pc 4-7cycloalkenyl group-heteroaryl, (14)-(ch 2) pc 2-10ring is mixed alkyl, (15)-(ch 2) pc 2-10ring is mixed thiazolinyl, (16)-(ch 2) paryl, (17)-(ch 2) paryl-c 1-8alkyl, (18)-(ch 2) paryl-c 2-8thiazolinyl, (19)-(ch 2) paryl-c 2-8alkynyl-c 1-8alkyl, (20)-(ch 2) paryl-c 2-8alkynyl-c 3-7cycloalkyl, (21)-(ch 2) paryl-c 2-8alkynyl-c 3-7cycloalkenyl group, (22)-(ch 2) paryl-c 2-8alkynyl-c 2-10ring is mixed alkyl, (23)-(ch 2) paryl-c 2-8alkynyl-c 2-10ring is mixed thiazolinyl, (24)-(ch 2) paryl-c 2-8alkynyl-aryl, (25)-(ch 2) paryl-c 2-8alkynyl-heteroaryl, (26)-(ch 2) paryl-c 3-7cycloalkyl, (27)-(ch 2) paryl-c 3-7cycloalkenyl group, (28)-(ch 2) paryl-c 2-10ring is mixed alkyl, (29)-(ch 2) paryl-c 2-10ring is mixed thiazolinyl, (30)-(ch 2) paryl-aryl, (31)-(ch 2) paryl-heteroaryl, (32)-(ch 2) pheteroaryl, (33)-(ch 2) pheteroaryl-c 3-7cycloalkyl, (34)-(ch 2) pheteroaryl-c 2-10ring is mixed alkyl, (35)-(ch 2) pheteroaryl-c 2-10ring is mixed thiazolinyl, (36)-(ch 2) pheteroaryl-aryl, (37)-(ch 2) pheteroaryl-heteroaryl, (38)-c 2-6thiazolinyl-alkyl, (39)-c 2-6thiazolinyl-aryl, (40)-c 2-6alkenyl-heteroaryl, (41)-c 2-6thiazolinyl-c 3-7cycloalkyl, (42)-c 2-6thiazolinyl-c 3-7cycloalkenyl group, (43)-c 2-6thiazolinyl-c 2-7ring is mixed alkyl, (44)-c 2-6thiazolinyl-c 2-7ring is mixed thiazolinyl, (45)-c 2-6alkynyl-(ch 2) 1-3-o-aryl, (46)-c 2-6alkynyl-alkyl, (47)-c 2-6alkynyl-aryl, (48)-c 2-6alkynyl-heteroaryl, (49)-c 2-6alkynyl-c 3-7cycloalkyl, (50)-c 2-6alkynyl-c 3-7cycloalkenyl group, (51)-c 2-6alkynyl-c 2-7ring is mixed alkyl, (52)-c 2-6alkynyl-c 2-7ring is mixed thiazolinyl, and (53) – c (o) nh-(ch 2) 0-3phenyl, wherein each ch 2be unsubstituted or be selected from following substituent group by 1 or 2 and replace: halogen, cf 3,-oh ,-nh 2, – c 1-6alkyl ,-oc 1-6alkyl, – nhc 1-6wan ji is with – n (c 1-6alkyl) 2, wherein each alkyl, thiazolinyl, alkynyl, cycloalkyl, cycloalkenyl group, ring mix alkyl, ring mix thiazolinyl, phenyl, aryl and heteroaryl be unsubstituted or by 1,2,3 or 4 independently selected from r asubstituent group replace, condition is r 1and r 2in at least one and only one be selected from: hydrogen, halogen ,-cn ,-cf 3,-c 1-6alkyl, – c 2-6thiazolinyl and-c 2-6alkynyl; r 3and r 4do not exist independently of one another or be selected from: (1) hydrogen,(2) halogen,(3) – c 1-6alkyl, (4) – c 2-6thiazolinyl, (5) – c 2-6alkynyl, (6) – c 3-10cycloalkyl, (7) – c 3-10cycloalkenyl group, (8) aryl,(9) heteroaryl,(10) –cn，(11) –cf 3， (12) –oh，(13)-oc 1-6alkyl, (14) –nh 2， (15) – nhc 1-6alkyl, (16) – n (c 1-6alkyl) 2, (17)-sc 1-6alkyl, (18)-soc 1-6alkyl, (19) – so 2c 1-6alkyl, (20) – nhso 2c 1-6alkyl, (21) – nhc (o) c 1-6alkyl, (22) – so 2nhc 1-6alkyl, and (23) – c (o) nhc 1-6alkyl; r 5be selected from: (1) hydrogen,(2)-c 1-6alkyl, (3)-c 1-6thiazolinyl, (4) -(ch 2) uoh， (5)-ch 2co 2h, and (6)-ch 2co 2c 1-6alkyl; each r aindependently selected from: (1)-(ch 2) m-halogen, (2) oxo,(3) -(ch 2) moh， (4) -(ch 2) mn(r j) 2， (5) -(ch 2) mno 2， (6) -(ch 2) mcn， (7)-c 1-6alkyl, (8) -(ch 2) mcf 3， (9) -(ch 2) mocf 3， (10)-o-(ch 2) m-oc 1-6alkyl, (11) -(ch 2) mn(r j)c(o)r f， (12) -(ch 2) mn(r j)co 2r f， (13) -(ch 2) mc(=n-oh)n(r j) 2， (14)-(ch 2) moc 1-6alkyl, (15)-(ch 2) mo-(ch 2) m-c 3-7cycloalkyl, (16)-(ch 2) mo-(ch 2) m-c 2-7ring is mixed alkyl, (17)-(ch 2) mo-(ch 2) m-aryl, (18)-(ch 2) mo-(ch 2) m-heteroaryl, (19)-(ch 2) msc 1-6alkyl, (20)-(ch 2) ms (o) c 1-6alkyl, (21)-(ch 2) mso 2c 1-6alkyl, (22)-(ch 2) mo-so 2c 1-6alkyl, (23)-(ch 2) mso 2(ch 2) m-c 3-7cycloalkyl, (24)-(ch 2) mso 2(ch 2) m-c 2-7ring is mixed a...
신규 아자벤즈이미다졸 헥사히드로푸로[3,2-B]푸란 유도체하기 구조 화학식 I의 신규 화합물은 AMP-단백질 키나제의 활성화제이고, AMPK 활성화 단백질 키나제에 의해 매개되는 질환의 치료, 예방 및 억제에 유용할 수 있다. 본 발명의 화합물은 제2형 당뇨병, 고혈당증, 대사 증후군, 비만, 고콜레스테롤혈증 및 고혈압의 치료에 유용할 수 있다. <화학식 I>하기 구조 화학식 I의 화합물 또는 그의 제약상 허용되는 염.<화학식 I>[이미지]상기 식에서,T는 CR3, N 및 N-옥시드로 이루어진 군으로부터 선택되고;U는 CR1, N 및 N-옥시드로 이루어진 군으로부터 선택되고;V는 CR2, N 및 N-옥시드로 이루어진 군으로부터 선택되고;W는 CR4, N 및 N-옥시드로 이루어진 군으로부터 선택되며,단 T, U, V 및 W 중 적어도 1개는 N 또는 N-옥시드이고;X는(1) -CH2-,(2) -CHF-,(3) -CF2-,(4) -S-,(5) -O-,(6) -O-CH2-,(7) -O-CH2CH2-,(8) -NH-,(9) -C(O)-,(10) -NHC(O)-,(11) -C(O)NH-,(12) -NHSO2-,(13) -SO2NH-, 및(14) -CO2-로부터 선택되고,여기서 각각의 CH2는 비치환되거나 또는 히드록시, 할로겐, NH2, C1-6알킬, CO2H, CO2C1-6알킬, COC1-6알킬, 페닐 및 -CH2페닐로부터 선택된 1 또는 2개의 치환기로 치환되고, 여기서 각각의 NH는 비치환되거나 또는 C1-6알킬, CO2H, CO2C1-6알킬, COC1-6알킬, 페닐 및 -CH2페닐로부터 선택된 1개의 치환기로 치환되고;Y는[이미지]로부터 선택되고,여기서 A는 CH2, NH, NC1-6알킬, O 및 S로부터 선택되고, 여기서 Y는 비치환되거나 또는 Rb로부터 선택된 1, 2, 3 또는 4개의 치환기로 치환되고;Z는(1) NR5,(2) -S-, 및(3) -O-로부터 선택되고;각각의 R1 및 R2는 독립적으로(1) 수소,(2) 할로겐,(3) CN,(4) CF3,(5) -C1-6알킬,(6) -C2-6알케닐,(7) -C2-6알키닐,(8) -(CH2)pC3-10시클로알킬,(9) -(CH2)pC3-7시클로알킬-아릴,(10) -(CH2)pC3-7시클로알킬-헤테로아릴,(11) -(CH2)pC4-10시클로알케닐,(12) -(CH2)pC4-7시클로알케닐-아릴,(13) -(CH2)pC4-7시클로알케닐-헤테로아릴,(14) -(CH2)pC2-10시클로헤테로알킬,(15) -(CH2)pC2-10시클로헤테로알케닐,(16) -(CH2)p아릴,(17) -(CH2)p아릴-C1-8알킬,(18) -(CH2)p아릴-C2-8알케닐,(19) -(CH2)p아릴-C2-8알키닐-C1-8알킬,(20) -(CH2)p아릴-C2-8알키닐-C3-7시클로알킬,(21) -(CH2)p아릴-C2-8알키닐-C3-7시클로알케닐,(22) -(CH2)p아릴-C2-8알키닐-C2-10시클로헤테로알킬,(23) -(CH2)p아릴-C2-8알키닐-C2-10시클로헤테로알케닐,(24) -(CH2)p아릴-C2-8알키닐-아릴,(25) -(CH2)p아릴-C2-8알키닐-헤테로아릴,(26) -(CH2)p아릴-C3-7시클로알킬,(27) -(CH2)p아릴-C3-7시클로알케닐,(28) -(CH2)p아릴-C2-10시클로헤테로알킬,(29) -(CH2)p아릴-C2-10시클로헤테로알케닐,(30) -(CH2)p아릴-아릴,(31) -(CH2)p아릴-헤테로아릴,(32) -(CH2)p헤테로아릴,(33) -(CH2)p헤테로아릴-C3-7시클로알킬,(34) -(CH2)p헤테로아릴-C2-10시클로헤테로알킬,(35) -(CH2)p헤테로아릴-C2-10시클로헤테로알케닐,(36) -(CH2)p헤테로아릴-아릴,(37) -(CH2)p헤테로아릴-헤테로아릴,(38) -C2-6알케닐-알킬,(39) -C2-6알케닐-아릴,(40) -C2-6알케닐-헤테로아릴,(41) -C2-6알케닐-C3-7시클로알킬,(42) -C2-6알케닐-C3-7시클로알케닐,(43) -C2-6알케닐-C2-7시클로헤테로알킬,(44) -C2-6알케닐-C2-7시클로헤테로알케닐,(45) -C2-6 알키닐-(CH2)1-3-O-아릴,(46) -C2-6알키닐-알킬,(47) -C2-6알키닐-아릴,(48) -C2-6알키닐-헤테로아릴,(49) -C2-6알키닐-C3-7시클로알킬,(50) -C2-6알키닐-C3-7시클로알케닐,(51) -C2-6알키닐-C2-7시클로헤테로알킬,(52) -C2-6알키닐-C2-7시클로헤테로알케닐, 및(53) -C(O)NH-(CH2)0-3페닐로부터 선택되고,여기서 각각의 CH2는 비치환되거나 또는 할로겐, CF3, -OH, -NH2, -C1-6알킬, -OC1-6알킬, -NHC1-6알킬, 및 -N(C1-6알킬)2로부터 선택된 1 또는 2개의 치환기로 치환되고, 여기서 각각의 알킬, 알케닐, 알키닐, 시클로알킬, 시클로알케닐, 시클로헤테로알킬, 시클로헤테로알케닐, 페닐, 아릴 및 헤테로아릴은 비치환되거나 또는 Ra로부터 독립적으로 선택된 1, 2, 3 또는 4개의 치환기로 치환되며,단 R1 및 R2 중 적어도 1개 및 단 1개는 수소, 할로겐, -CN, -CF3, -C1-6알킬, -C2-6알케닐 및 -C2-6알키닐로 이루어진 군으로부터 선택되고;R3 및 R4는 각각 독립적으로 부재하거나 또는(1) 수소,(2) 할로겐,(3) -C1-6알킬,(4) -C2-6알케닐,(5) -C2-6알키닐,(6) -C3-10시클로알킬,(7) -C3-10시클로알케닐,(8) 아릴,(9) 헤테로아릴,(10) -CN,(11) -CF3,(12) -OH,(13) -OC1-6알킬,(14) -NH2,(15) -NHC1-6알킬,(16) -N(C1-6알킬)2,(17) -SC1-6알킬,(18) -SOC1-6알킬,(19) -SO2C1-6알킬,(20) -NHSO2C1-6알킬,(21) -NHC(O)C1-6알킬,(22) -SO2NHC1-6알킬, 및(23) -C(O)NHC1-6알킬로부터 선택되고;R5는(1) 수소,(2) -C1-6알킬,(3) -C1-6알케닐,(4) -(CH2)uOH,(5) -CH2CO2H, 및(6) -CH2CO2C1-6알킬로부터 선택되고;각각의 Ra는 독립적으로(1) -(CH2)m-할로겐,(2) 옥소,(3) -(CH2)mOH,(4) -(CH2)mN(Rj)2,(5) -(CH2)mNO2,(6) -(CH2)mCN,(7) -C1-6알킬,(8) -(CH2)mCF3,(9) -(CH2)mOCF3,(10) -O-(CH2)m-OC1-6 알킬,(11) -(CH2)mN(Rj)C(O)Rf,(12) -(CH2)mN(Rj)CO2Rf,(13) -(CH2)mC(=N-OH)N(Rj)2,(14) -(CH2)mOC1-6알킬,(15) -(CH2)mO-(CH2)m-C3-7시클로알킬,(16) -(CH2)mO-(CH2)m-C2-7시클로헤테로알킬,(17) -(CH2)mO-(CH2)m-아릴,(18) -(CH2)mO-(CH2)m-헤테로아릴,(19) -(CH2)mSC1-6알킬,(20) -(CH2)mS(O)C1-6알킬,(21) -(CH2)mSO2C1-6알킬,(22) -(CH2)mO-SO2C1-6알킬,(23) -(CH2)mSO2(CH2)m-C3-7시클로알킬,(24) -(CH2)mSO2(CH2)m-C2-7시클로헤테로알킬,(25) -(CH2)mSO2(CH2)m-아릴,(26) -(CH2)mSO2(CH2)m-헤테로아릴,(27) -(CH2)mSO2NH2,(28) -(CH2)mSO2NHC1-6알킬,(29) -(CH2)mSO2NHC3-7시클로알킬,(30) -(CH2)mSO2NHC2-7시클로헤테로알킬,(31) -(CH2)mSO2NH-아릴,(32) -(CH2)mSO2NH-헤테로아릴,(33) -(CH2)mNHSO2-C1-6알킬,(34) -(CH2)mNHSO2-C3-7시클로알킬,(35) -(CH2)mNHSO2-C2-7시클로헤테로알킬,(36) -(CH2)mNHSO2-아릴,(37) -(CH2)mNHSO2NH-헤테로아릴,(38) -(CH2)mN(Rj)-C1-6알킬,(39) -(CH2)mN(Rj)-C3-7시클로알킬,(40) -(CH2)mN(Rj)-(CH2)m-C3-7시클로알킬,(41) -(CH2)mN(Rj)-C2-7시클로헤테로알킬,(42) -(CH2)mN(Rj)-(CH2)m-C2-7시클로헤테로알킬,(43) -(CH2)mN(Rj)-C2-7시클로헤테로알케닐,(44) -(CH2)mN(Rj)-(CH2)m-C2-7시클로헤테로알케닐,(45) -(CH2)mN(Rj)-아릴,(46) -(CH2)mN(Rj)-(CH2)m-아릴,(47) -(CH2)mN(Rj)-헤테로아릴,(48) -(CH2)mN(Rj)-(CH2)m-헤테로아릴,(49) -(CH2)mC(O)Rf,(50) -(CH2)mC(O)N(Rj)2,(51) -(CH2)mN(Rj)C(O)N(Rj)2,(52) -(CH2)mCO2H,(53) -(CH2)mOCOH,(54) -(CH2)mCO2Rf,(55) -(CH2)mOCORf,(56) -(CH2)mC3-7시클로알킬,(57) -(CH2)mC3-7시클로알케닐,(58) -(CH2)mC2-6시클로헤테로알킬,(59) -(CH2)mC2-6시클로헤테로알케닐,(60) -(CH2)m아릴, 및(61) -(CH2)m헤테로아릴로 이루어진 군으로부터 선택되고,여기서 각각의 CH2는 비치환되거나 또는 옥소, -OH, -(CH2)1-3OH, -CN, -NH2, -NH(C1-6알킬), -N(C1-6알킬)2, -C1-6알킬, 1-5개의 OH로 치환된 -C1-6알킬, -OC1-6알킬, 할로겐, -CH2F, -CHF2, -CF3, -CO2H, -CO2C1-6알킬, -C3-7시클로알킬, 페닐, CH2페닐, 헤테로아릴 및 CH2헤테로아릴로부터 선택된 1 또는 2개의 치환기로 치환되고, 여기서 알킬, 시클로알킬, 시클로알케닐, 시클로헤테로알킬, 시클로헤테로알케닐, 아릴 및 헤테로아릴은 비치환되거나 또는 옥소, -OH, -(CH2)1-5OH, -CN, -NH2, -NH(C1-6알킬), -N(C1-6알킬)2, -C1-6알킬, 1-5개의 OH로 치환된 -C1-6알킬, -OC1-6알킬, 할로겐, -CH2F, -CHF2, -CF3, 1, 2 또는 3개의 -OH로 임의로 치환된 -(CH2)1-5CF3, -CO2H, -CO2C1-6알킬, -SO2C1-6알킬, -C3-7시클로알킬, 페닐, CH2페닐, 헤테로아릴 및 CH2헤테로아릴로부터 선택된 1, 2, 3 또는 4개의 치환기로 치환되고;각각의 Rb는 독립적으로(1) 수소,(2) -C1-6알킬,(3) -C1-6알케닐,(4) -(CH2)nC3-10시클로알킬,(5) -(CH2)nC3-10시클로알케닐,(6) -(CH2)nC2-10시클로헤테로알킬,(7) -(CH2)nC2-10시클로헤테로알케닐,(8) -(CH2)n아릴,(9) -(CH2)n헤테로아릴,(10) ...