公开(公告)号：CA2455861A1

公开(公告)日：2003-02-20

申请号：CA2455861

申请日：2002-08-01

Applicant: SCHERING CORP

Inventor： PISSARNITSKI DMITRI A ,  JOSIEN HUBERT B ,  ASBEROM THEODROS ,  CLADER JOHN W

IPC: A61K31/40 ,  A61K31/445 ,  A61K31/4462 ,  A61K31/4468 ,  A61K31/453 ,  A61K31/4535 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61P25/00 ,  A61P25/28 ,  A61P43/00 ,  C07D207/14 ,  C07D211/56 ,  C07D211/58 ,  C07D211/62 ,  C07D211/96 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D405/12 ,  C07D409/06 ,  C07D413/06 ,  C07D417/06 ,  C07D405/06 ,  A61K31/4709

Abstract: Novel aryl and heteroaryl sulfonamides are disclosed. The sulfonamides, whic h are gamma secretase inhibitors, are represented by the formula: (I), wherein Ar1 and Ar2 independently represent aryl or heteroaryl and Y represents a bo nd or a (C(R3)2)1-3 group. Also disclosed is a method of inhibiting gamma secretase, and a method of treating Alzheimer s disease using the compounds of formula I.

公开(公告)号：AT227708T

公开(公告)日：2002-11-15

申请号：AT97932321

申请日：1997-07-08

Applicant: SCHERING CORP

Inventor： ASBEROM THEODROS ,  LOWE DEREK B ,  GREEN MICHAEL J

IPC: A61K31/00 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4468 ,  A61K31/4545 ,  A61K45/06 ,  A61P25/28 ,  C07D211/58 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14

Abstract: 1,4-Di-substituted piperidine muscarinic antagonists of formula (I) or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein X is a bond, -O-, -S-, -SO-, -SO2-, -CO-, -C(OR )2-, -CH2-O-, -O-CH2-, -CH=CH-, -CH2-, -CH(C1-C6 alkyl)-, -C(C1-C6 alkyl)2-, -CONR -, -NR CO-, -SO2NR - or -NR SO2-; R is C3-C6 cycloalkyl, (a), (b), (c), (d), (e), optionally substituted phenyl or optionally substituted pyridyl; R is H, -CN, -CF3, alkyl, cycloalkyl, cycloalkenyl, alkenyl, -COR , -COO(alkyl, aryl, heteroaryl, alkylaryl or alkylheteroaryl), alkylaryl, alkylheteroaryl or -CON(R )2; R is cycloalkyl, cycloalkenyl, t-butoxycarbonyl or optionally substituted 4-piperidinyl; R and R are H, halo, -CF3, alkyl, alkoxy or -OH; R and R are H, alkyl, -CF3, alkoxy, -OH, alkylcarbonyl, alkoxycarbonyl, R CONH-, R OCONH-, R NHCONH- or NH2CONR -; R is H or alkyl, or the two R groups may form -(CH2)2-4; R is H, alkyl, cycloalkyl, -(alkyl)COOR , aryl, heteroaryl, alkylaryl, alkylheteroaryl and adamantyl; R is H or alkyl; R is H, C1-C20 alkyl, C1-C6 cycloalkyl, aryl or heteroaryl; and R is H, C1-C6 alkyl, aryl or heteroaryl; useful for treating cognitive disorders such as Alzheimer's disease are disclosed, as well as pharmaceutical compositions and methods of preparation. Also disclosed are combinations of compounds of formula (I) capable of enhancing ACh release with ACh'ase inhibitors.

公开(公告)号：PL341114A1

公开(公告)日：2001-03-26

申请号：PL34111498

申请日：1998-11-23

Applicant: SCHERING CORP

Inventor： CHACKALAMANNIL SAMUEL ,  ASBEROM THEODROS ,  XIA YAN ,  DOLLER DARIO ,  CLASBY MARTIN C ,  CZARNIECKI MICHAEL F

IPC: C07D491/056 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/427 ,  A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/4738 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61P7/02 ,  A61P9/00 ,  A61P9/04 ,  A61P9/06 ,  A61P9/10 ,  A61P9/12 ,  A61P35/00 ,  A61P43/00 ,  C07D401/06 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D491/04 ,  C07D493/04 ,  C07D493/10

Abstract: Heterocyclic-substituted tricyclics of formula (I) or a pharmaceutically acceptable salt thereof, wherein: the single dotted line represents an optional double bond; the double dotted line represents an optional single bond; n is 0-2; Q is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Het is an optionally substituted mono-, bi- or tricyclic heteroaromatic group; B is -(CH2)n3-, wherein n3 is 0-5, -CH2-O-, -CH2S-, -CH2-NR -, -C(O)NR -. -NR C(O)-, (a), optionally substituted alkenyl or optionally substituted alkynyl; X is -O- or -NR - when the double dotted line represents a single bond, or X is -OH or -NHR when the bond is absent; Y is =O, =S, (H, H), (H, OH) or (H, C1-C6 alkoxy) when the double dotted line represents a single bond, or when the bond is absent, Y is =O, (H, H), (H, OH), (H, SH) or (H, C1-C6 alkoxy); R is absent when the double dotted line represents a single bond and is H, -NR R , or -OR when the bond is absent; or Y is (A) or (B) and R is H or C1-C6 alkyl; are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds.

公开(公告)号：ID24726A

公开(公告)日：2000-08-03

申请号：ID20000993

申请日：1998-11-23

Applicant: SCHERING CORP

Inventor： CHACKALAMANNIL SAMUEL ,  ASBEROM THEODROS ,  XIA YAN ,  DOLLER DARIO ,  CLASBY MARTIN C ,  CZARNIECKI MICHAEL F

IPC: C07D491/056 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/427 ,  A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/4738 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61P7/02 ,  A61P9/00 ,  A61P9/04 ,  A61P9/06 ,  A61P9/10 ,  A61P9/12 ,  A61P35/00 ,  A61P43/00 ,  C07D401/06 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D491/04 ,  C07D493/04 ,  C07D493/10 ,  D21H27/00 ,  D21H21/20 ,  C08F8/00 ,  D21H17/37 ,  D06M15/347 ,  D06M15/263 ,  D06M15/285

Abstract: Heterocyclic-substituted tricyclics of formula (I) or a pharmaceutically acceptable salt thereof, wherein: the single dotted line represents an optional double bond; the double dotted line represents an optional single bond; n is 0-2; Q is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Het is an optionally substituted mono-, bi- or tricyclic heteroaromatic group; B is -(CH2)n3-, wherein n3 is 0-5, -CH2-O-, -CH2S-, -CH2-NR -, -C(O)NR -. -NR C(O)-, (a), optionally substituted alkenyl or optionally substituted alkynyl; X is -O- or -NR - when the double dotted line represents a single bond, or X is -OH or -NHR when the bond is absent; Y is =O, =S, (H, H), (H, OH) or (H, C1-C6 alkoxy) when the double dotted line represents a single bond, or when the bond is absent, Y is =O, (H, H), (H, OH), (H, SH) or (H, C1-C6 alkoxy); R is absent when the double dotted line represents a single bond and is H, -NR R , or -OR when the bond is absent; or Y is (A) or (B) and R is H or C1-C6 alkyl; are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds.

公开(公告)号：NZ333801A

公开(公告)日：2000-04-28

申请号：NZ33380197

申请日：1997-08-06

Applicant: SCHERING CORP

Inventor： LOWE DEREK B ,  CHANG WEI K ,  KOZLOWSKI JOSEPH A ,  BERGER JOEL G ,  MCQUADE ROBERT ,  BARNETT ALLEN ,  SHERLOCK MARGARET ,  TOM WING ,  DUGAR SUNDEEP ,  CHEN LIAN-YONG ,  CLADER JOHN W ,  CHACKALAMANNIL SAMUEL ,  WANG YUGUANG ,  MCCOMBIE STUART W ,  TAGAT JAYARAM R ,  VICE SUSAN F ,  VACCARO WAYNE D ,  GREEN MICHAEL J ,  BROWNE MARGARET E ,  ASBEROM THEODROS ,  BOYLE CRAIG D ,  JOSIEN HUBERT B

IPC: A61K31/00 ,  A61K31/435 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  C07D211/58 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/496 ,  A61K31/50 ,  A61K31/501 ,  A61K45/00 ,  A61P25/28 ,  C07D211/24 ,  C07D211/32 ,  C07D211/96 ,  C07D239/34 ,  C07D257/04 ,  C07D295/02 ,  C07D295/03 ,  C07D295/084 ,  C07D295/088 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/145 ,  C07D295/15 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

Abstract: Di-N-substituted piperazine or 1,4 di-substituted piperidine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) wherein R, R1, R2, R3, R4, R21, R27, R28, X, Y and Z as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula with acetylcholinesterase inhibitors.

公开(公告)号：HK1018776A1

公开(公告)日：2000-01-07

申请号：HK99103789

申请日：1999-09-02

Applicant: SCHERING CORP

Inventor： LOWE DEREK B ,  CHANG WEI K ,  KOZLOWSKI JOSEPH A ,  BERGER JOEL G ,  MCQUADE ROBERT ,  BARNETT ALLEN ,  SHERLOCK MARGARET ,  TOM WING ,  DUGAR SUNDEEP ,  CHEN LIAN-YONG ,  CLADER JOHN W ,  CHACKALAMANNIL SAMUEL ,  WANG YUGUANG ,  MCCOMBIE STUART W ,  TAGAT JAYARAM R ,  VICE SUSAN F ,  VACCARO WAYNE D ,  GREEN MICHAEL J ,  BROWNE MARGARET E ,  ASBEROM THEODROS ,  BOYLE CRAIG D ,  JOSIEN HUBERT B

IPC: C07D211/58 ,  A61K31/00 ,  A61K31/435 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/496 ,  A61K31/50 ,  A61K31/501 ,  A61K45/00 ,  A61P25/28 ,  C07D211/24 ,  C07D211/32 ,  C07D211/96 ,  C07D239/34 ,  C07D257/04 ,  C07D295/02 ,  C07D295/03 ,  C07D295/084 ,  C07D295/088 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/145 ,  C07D295/15 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D ,  A61K

Abstract: Di-N-substituted piperazine or 1,4 di-substituted piperadine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) wherein R, R1, R2, R3, R4, R21, R27, R28, X, Y, and Z are as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula with acetylcholinesterase inhibitors.

公开(公告)号：NZ303415A

公开(公告)日：1999-10-28

申请号：NZ30341596

申请日：1996-02-16

Applicant: SCHERING CORP

Inventor： LOWE DEREK ,  CHANG WEI ,  KOZLOWSKI JOSEPH ,  BERGER JOEL G ,  MCQUADE ROBERT ,  BARNETT ALLEN ,  SHERLOCK MARGARET ,  TOM WING ,  DUGAR SUNDEEP ,  CHEN LIAN-YONG ,  CLADER JOHN W ,  CHACKALAMANNIL SAMUEL ,  WANG YUGUANG ,  MCCOMBIE STUART W ,  TAGAT JAYARAM ,  VICE SUSAN F ,  VACCARO WAYNE ,  GREEN MICHAEL J ,  BROWNE MARGARET E ,  ASBEROM THEODROS

IPC: C07D295/08 ,  A61K31/335 ,  A61K31/357 ,  A61K31/36 ,  A61K31/365 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4468 ,  A61K31/451 ,  A61K31/495 ,  A61K31/496 ,  A61K31/505 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/5377 ,  A61P25/28 ,  C07D211/14 ,  C07D211/22 ,  C07D211/24 ,  C07D211/26 ,  C07D211/32 ,  C07D211/58 ,  C07D211/62 ,  C07D239/34 ,  C07D257/04 ,  C07D271/06 ,  C07D295/02 ,  C07D295/03 ,  C07D295/084 ,  C07D295/088 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/12 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/14 ,  C07D295/145 ,  C07D295/15 ,  C07D307/33 ,  C07D309/12 ,  C07D317/28 ,  C07D317/62 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D401/10 ,  C07D403/10 ,  C07D407/04 ,  C07D413/10

Abstract: Di-N-substituted piperazine or 1,4 di-substituted piperadine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) wherein R, R1, R2, R3, R4, R21, R27, R28, X, Y, and Z are as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula or other compounds capable of enhancing acetylcholine release with acetylcholinesterase inhibitors.

公开(公告)号：AU1415899A

公开(公告)日：1999-06-15

申请号：AU1415899

申请日：1998-11-23

Applicant: SCHERING CORP

Inventor： CHACKALAMANNIL SAMUEL ,  ASBEROM THEODROS ,  XIA YAN ,  DOLLER DARIO ,  CLASBY MARTIN C ,  CZARNIECKI MICHAEL F

IPC: C07D491/056 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/427 ,  A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/4738 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61P7/02 ,  A61P9/00 ,  A61P9/04 ,  A61P9/06 ,  A61P9/10 ,  A61P9/12 ,  A61P35/00 ,  A61P43/00 ,  C07D401/06 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D491/04 ,  C07D493/04 ,  C07D493/10

Abstract: Heterocyclic-substituted tricyclics of formula (I) or a pharmaceutically acceptable salt thereof, wherein: the single dotted line represents an optional double bond; the double dotted line represents an optional single bond; n is 0-2; Q is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Het is an optionally substituted mono-, bi- or tricyclic heteroaromatic group; B is -(CH2)n3-, wherein n3 is 0-5, -CH2-O-, -CH2S-, -CH2-NR -, -C(O)NR -. -NR C(O)-, (a), optionally substituted alkenyl or optionally substituted alkynyl; X is -O- or -NR - when the double dotted line represents a single bond, or X is -OH or -NHR when the bond is absent; Y is =O, =S, (H, H), (H, OH) or (H, C1-C6 alkoxy) when the double dotted line represents a single bond, or when the bond is absent, Y is =O, (H, H), (H, OH), (H, SH) or (H, C1-C6 alkoxy); R is absent when the double dotted line represents a single bond and is H, -NR R , or -OR when the bond is absent; or Y is (A) or (B) and R is H or C1-C6 alkyl; are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds.

公开(公告)号：CA2309352A1

公开(公告)日：1999-06-03

申请号：CA2309352

申请日：1998-11-23

Applicant: SCHERING CORP

Inventor： ASBEROM THEODROS ,  CZARNIECKI MICHAEL F ,  XIA YAN ,  CLASBY MARTIN C ,  CHACKALAMANNIL SAMUEL ,  DOLLER DARIO

IPC: C07D491/056 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/427 ,  A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/4738 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61P7/02 ,  A61P9/00 ,  A61P9/04 ,  A61P9/06 ,  A61P9/10 ,  A61P9/12 ,  A61P35/00 ,  A61P43/00 ,  C07D401/06 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D491/04 ,  C07D493/04 ,  C07D493/10 ,  C07D221/00 ,  C07D317/00

Abstract: Heterocyclic-substituted tricyclics of formula (I) or a pharmaceutically acceptable salt thereof, wherein: the single dotted line represents an optional double bond; the double dotted line represents an optional single bond; n is 0-2; Q is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Het is an optionally substituted mono-, bi- or tricyclic heteroaromatic group; B is -(CH2)n3-, wherein n3 is 0-5, -CH2-O-, -CH2S-, -CH2-NR6-, -C(O)NR6-. -NR6C(O)-, (a), optionally substituted alkenyl or optionally substituted alkynyl; X is -O- or -NR6- when the double dotted line represents a single bond, or X is -OH or -NHR20 when the bond is absent; Y is =O, =S, (H, H), (H, OH) or (H, C1-C6 alkoxy) when the double dotted line represents a single bond, or when the bond is absent, Y is =O, (H, H), (H, OH), (H, SH) or (H, C1-C6 alkoxy); R15 is absent when the double dotted line represents a single bond and is H, -NR18R19, or -OR17 when the bond is absent; or Y is (A) or (B) and R15 is H or C1-C6 alkyl; are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds.

公开(公告)号：ZA977011B

公开(公告)日：1998-02-06

申请号：ZA977011

申请日：1997-08-06

Applicant: SCHERING CORP

Inventor： LOWE DEREK B ,  BERGER JOEL G ,  SHERLOCK MARGARET ,  CHEN LIAN-YONG ,  WANG YUGUANG ,  VICE SUSAN F ,  BROWNE MARGARET E ,  JOSIEN HUBERT B ,  CHANG WEI K ,  MCQUADE ROBERT ,  TOM WING ,  CLADER JOHN W ,  MCCOMBIE STUART W ,  VACCARO WAYNE D ,  ASBEROM THEODROS ,  KOZLOWSKI JOSEPH A ,  BARNETT ALLEN ,  DUGAR SUNDEEP ,  CHACKALAMANNIL SAMUEL ,  TAGAT JAYARAM R ,  GREEN MICHAEL J ,  BOYLE CRAIG D

IPC: A61K31/00 ,  A61K31/435 ,  A61K31/4427 ,  C07D211/58 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/496 ,  A61K31/50 ,  A61K31/501 ,  A61K45/00 ,  A61P25/28 ,  C07D211/24 ,  C07D211/32 ,  C07D211/96 ,  C07D239/34 ,  C07D257/04 ,  C07D295/02 ,  C07D295/03 ,  C07D295/084 ,  C07D295/088 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/145 ,  C07D295/15 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D ,  A61K ,  A61J

Abstract: Di-N-substituted piperazine or 1,4 di-substituted piperadine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) wherein R, R1, R2, R3, R4, R21, R27, R28, X, Y, and Z are as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula with acetylcholinesterase inhibitors.