公开(公告)号：US20100204224A1

公开(公告)日：2010-08-12

申请号：US11993557

申请日：2006-07-07

申请人： Richard Hamlyn ,  Glyn Addison ,  Christopher Geoffrey Earnshaw ,  Harry Finch ,  Mike Huckstep ,  Rosemary Lynch ,  Sarah Mellor

发明人： Richard Hamlyn ,  Glyn Addison ,  Christopher Geoffrey Earnshaw ,  Harry Finch ,  Mike Huckstep ,  Rosemary Lynch ,  Sarah Mellor

IPC分类号： A61K31/5377 ,  C07D471/08 ,  A61K31/4995 ,  C07D487/10 ,  A61K31/407 ,  C07D487/04 ,  A61P13/10 ,  A61P25/00

CPC分类号： C07D487/04 ,  C07D487/08 ,  C07D487/10

摘要： Compounds of the formula (I), and pharmaceutically acceptable salts thereof, are found to be antagonists of SNS sodium channels. They are therefore useful as analgesic and neuroprotective agents; wherein (1) represents (A), (B) or (C); R1 represents: (a) -L-A or L′-A′ wherein L represents a bond or a C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl moiety, A represents a phenyl, 5- to 10-membered heteroaryl, C3-C6 carbocyclyl or 5- to 10 membered heterocyclyl group, L′ represents a C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl moiety, and A′ represents -Het-A or —X-A wherein Het represents —O—, —S— or NR′, and X represents —CO—, —SO—, SO2—, —CO—O—, CO—S, CONR′, —O—CO—, —S—CO— or NR′—CO—, wherein R′ represents hydrogen or C1-C6 alkyl; (b) -L-A-A′ or -L-A-L-A wherein A′ is as defined above, each A is the same or different and is as defined above and each L is the same or different and is as defined above; (c) -A-Z-A wherein Z is -Het-L′, —X-L′, -L′-Het- or L′-X, wherein Het, L′ and X are as defined above and each A is the same or different and is as defined above; (d) -A-Het-Y or -A-X—Y wherein is [L′-Het]n-L′, [L′-Het]n-L′, -[L′-Het]n-A, -L′-B-L′, -L′-B-A or -A-L-A wherein n is from 1 to 4 and B is —X—, —NR′—CO—NR′, —O—CO—NR′— or —NR′—CO—O, and wherein X and L are as defined above, each A is the same or different and is as defined above, each L′ is the same or different and is as defined above, each R′ is the same or different and is as defined above and each Het is the same or different and is as defined above; or (e) -L-CR(A)(A′) or L-CR(A)(L-A) wherein R is hydrogen or C1-C4 alkyl, A′ is as defined above, each L is the same or different and is as defined above and each A is the same or different and is as defined above; R2 represents -L-A-, L′-A′, -L-A-A′ or L-A-L-A wherein L′ and A′ are as defined above, each L is the same or different and is as defined above and each A is the same or different and is as defined above J represents —NR3—, —O— or a direct bond wherein R3 represent s hydrogen C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl; p is an integer from 1 to 3; q is 1 or 2; and one of E and E′ is —CH2— and the other is a direct bond.

公开(公告)号：US20100105651A1

公开(公告)日：2010-04-29

申请号：US11993515

申请日：2006-07-07

申请人： Richard Hamlyn ,  David Callis ,  Christopher Geoffrey Earnshaw ,  Harry Finch ,  Mike Huckstep ,  Rosemary Lynch ,  Sarah Mellor

发明人： Richard Hamlyn ,  David Callis ,  Christopher Geoffrey Earnshaw ,  Harry Finch ,  Mike Huckstep ,  Rosemary Lynch ,  Sarah Mellor

IPC分类号： A61K31/397 ,  C07D205/04 ,  C07D401/02 ,  A61P1/00 ,  A61P13/10 ,  A61P25/00

CPC分类号： A61K31/397

摘要： Compounds of the formula (I), and pharmaceutically acceptable salts thereof, are found to be antagonists of SNS sodium channels. They are therefore useful as analgesic and neuroprotective agents, formula (I): R1 represents: (a) -L-A or -L′-A′ wherein L represents a bond or a C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl moiety, A represents a phenyl, 5- to 10-membered heteroaryl, C3-C6 carbocyclyl or 5- to 10-membered heterocyclyl group, L′ represents a C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl moiety, and A′ represents -Het-A or —X-A wherein Het represents —O—, —S— or —NR1—, and X represents —CO—, —SO—, —SO2—, —CO—O—, —CO—S—, —CONR1—, —O—CO—, —S—CO— or —NR1—CO—, wherein R1 represents hydrogen or C1-C6 alkyl; (b) -L-CR(A)(A′) or -L-CR(A)(L-A) wherein R is hydrogen or C1-C4 alkyl, A′ is as defined above, each L is the same or different and is as defined above and each A′ is the same or different and is as defined above; (c) -L-A-A′ or -L-A-L-A wherein A′ and L are as defined above and each A is the same or different and is as defined above; or (d) -A-Z-A wherein Z is -Het-L′-, —X-L′-, -L′-Het- or -L′-X—, wherein Het, L′ and X are as defined above and each A is the same or different and is as defined above; J represents —NRS—, —O— or a direct bond; R5 represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl; R4 is represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl; and either R represents -L-A, -L-A′, -L-A-A′, -L-A-L-A, -L-CR(A)(L-A), -L-CR(A)(A′) or -L-CR(A)(L″) wherein L″ is -Het-L′, —CONH2 or —CO2H, and wherein A′, Het, X and R are as defined above, each L is the same or different and is as defined above, each A is the same or different and is as defined above and R3 represents hydrogen, C1-C6 alkyl C2-C6 alkynyl or (CO)-L′, wherein L is as defined above or R2 and R3 form, together with the nitrogen to which they are attached, a 5- to 10-membered heteroaryl or 5- to 10-membered heterocyclyl ring.