Tropane compounds

Abstract

The present invention provides novel tropane compounds and methods for their use.

1 . A compound having the formula: 
     
       
         
         
             
             
         
       
     
     Where:
 the 2-, 3-, 6-, or 7-positions are α or β; 
 the compounds are racemic or 1R- or 1S-configured; 
 X═O, NR 3 , NR 10 , CHR 3 , CHR 1 , CH 2 , CHW 1 , CW 1 W 1 , CO, S, SO, SO 2 , NSO 2 R 3 , NSO 2 R 11  or CX 2 W, with the N, C, O or S atom being a member of the ring; 
 Ar=Phenyl or 1-naphthyl or 2-naphthyl, unsubstituted or substituted with one or more group selected from: —H; —Br; —Cl; —I; —F; —OH; —CH 3 ; —OCH 3 ; —CF 3 ; —NO 2 ; —NH 2 ; —CN; —NHCOCH 3 , —C(CH 3 ) 3 , —C(CH 2 )CH 3 , (CH 2 ) q CH 3 , where q=0-6; —COCH 3 ; OAc; alkyl; alkenyl; alkynyl; allyl; isopropyl; isobutyl; wherein each substituent can be at the 2, 3 and/or 4 position of the ring; 
 W or X 2 ═H, OH, OCH 3 , OAc, OCOR 4 , CH 3 , (CH 2 ) n CH 3 , R 4 ; 
 W 1 ═H, Br, Cl, I, F, OH, OCH 3 , CF 3 , NO 2 , NH 2 , CN, NHCOCH 3 , N(CH 3 ) 2 , (CH 2 ) n CH 3 , COCH 3 , or C(CH 3 ) 3 ; 
 R 2 ═R 3 , OR 3 , isopropyl, isobutyl, OCOR 4 , OCOR 5 , W 1 , CH 2 R 3 , OCOR 3 , NHR 3 , COR 3 , (CH 2 ) n COOR 3 ; 
 R 3 ═H, CH 3 , CH 2 Ar, (CH 2 ) n Ar, Ar, alkyl, alkenyl or alkynyl, cycloalkylmethyl, CH 2 CH═CHZ, (CH 2 ) n OH, (CH 2 ) n OR 4 , CH═CHZ; CH 2 J-Maleimide, CH 2 JN-Maleimide where J=CH 2  or O; (CH 2 ) n OCOCH 3 ; (CH 2 ) n OCOCH 2 OCH 3 ; (CH 2 ) n -morpholine; (CH 2 ) n -piperidine; (CH 2 ) n -piperazine; 
 R 4 ═CH 3 , CH 2 CH 3 , alkyl, alkenyl, alkynyl, allyl, isopropyl, isobutyl; 
 R 5 ═H, CH 3 , (CH 3 ) 2 , (CH 2 ) n SO 3 Q, alkyl, (alkyl) 2 , alkenyl, alkynyl, Ar, OCH 3 ; 
 Q=K + , Na + , Li + , Ca 2+ , NH 4   + , RNH 3   + , or other pharmaceutically acceptable salts; 
 R 10 ═COR 4 , CH 2 OH, (CH 2 ) n OH, (CH 2 ) n OR 4 , (CH 2 ) n COOR 3 , (CH 2 ) n OCOR 3 ; 
 R 11 ═H, COOCH 3 , COOR 4 , COR 4 , CH 2 OH, (CH 2 ) n OH, (CH 2 ) n OR 4 , CR 3 ═NOR 3 , CH═NR 3 ; 
 R 6  and R 7  independently ═H, CH 3 , CH 2 CH 3 , (CH 2 ) r CH 3 , (CH 2 ) r Ar, isopropyl, isobutyl, CH═CH—(CH 2 ) r CH 3 , CH 2 CH═CH—(CH 2 ) r CH 3 , (CH 2 ) s CH═CH—(CH 2 ) r CH 3 , C≡C—(CH 2 ) r CH 3 , CH 2 C≡C—(CH 2 ) r CH 3 , (CH 2 ) s C≡C—(CH 2 ) r CH 3 , OCOR 3 , (CH 2 ) d OCOR 3 , COOR 3  or (CH 2 ) d COOR 3 ;
 d=1-6; 
 r=0-4; 
 s=0-4; 
 n=0-4; and 
 Z=F, Cl, I or Br. 
 
 
   
   
       2 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to  claim 1 . 
   
   
       3 . (canceled) 
   
   
       4 . A method of treating a medical condition comprising administering to a patient a compound according to  claim 1  said medical condition being attention deficit hyperactivity disorder (ADHD), Parkinson's disease, cocaine addiction, smoking cessation, weight reduction, obsessive-compulsive disorder, various forms of depression, traumatic brain injury, stroke or narcolepsy. 
   
   
       5 . A method of making a medicament for treating attention deficit hyperactivity disorder (ADHD), Parkinson's disease, cocaine addiction, smoking cessation, weight reduction, obsessive-compulsive disorder, various forms of depression, traumatic brain injury, stroke or narcolepsy, said method comprising formulating a compound according to  claim 1  into said medicament. 
   
   
       6 . A method of treating a medical condition comprising administering to a patient a compound according to  claim 1 , said medical condition being attention deficit hyperactivity disorder (ADHD); Parkinson's disease; cocaine addiction; smoking cessation; weight reduction; obsessive-compulsive disorder; various forms of depression; traumatic brain injury; stroke; narcolepsy; seasonal affective disorders; sexual dysfunction; sexual behavior disorders; learning deficit; disorders involving the release of acetylcholine, including memory deficits, senile dementia, dementia of aging, AIDS-dementia, pseudodementia, presenile dementia, autism, mutism, cognitive disorders, dyslexia, tardive dyskinesia, hyperkinesias, anxiety, panic disorders, paranoia, post-traumatic syndrome; social phobia, other phobias; psychosis; bipolar disorder and other psychiatric or clinical dysfunctions; mania; manic depression; schizophrenia (deficient form and productive form); acute or chronic extrapyramidal symptoms induced by neuroleptic agents; chronic fatigue syndrome; deficits of alertness, attention, arousal and vigilance; disorders of sleep and jet-lag; obesity, bulimia, anorexia nervosa and other eating disorders; cocaine and other drug addiction or misuse; alcoholism; neurological disorders; epilepsy; neurodegenerative diseases including Alzheimer Disease, Huntington Disease, Amyotrophic Lateral Sclerosis, Gilles de la Tourette syndrome; mild, moderate or severe pain of acute, chronic or recurrent character, pain caused by migraine, postoperative pain or phantom limb pain; disorders linked to decreased transmission of serotonin in mammals, including Ganser syndrome, migraine headache, pre-menstrual syndrome or late luteal phase syndrome or peripheral neuropathy. 
   
   
       7 . A method screening compounds for use as a treatment for altering monoamine transport, comprising exposing cells having associated monoamine transporters to a compound according to  claim 1 , and assessing binding of the compound to the cells. 
   
   
       8 . A method of diagnosing a disease or disorder that affects monoamine transport comprising labeling a compound of  claim 1 , administering the labeled compound to a patient, imaging the binding of the labeled compound in the patient, and comparing said imaged patient binding to a reference standard. 
   
   
       9 .- 11 . (canceled) 
   
   
       12 . A compound having one of the following formulae: 
     
       
         
         
             
             
         
       
       Where: 
       the 2-, 3-, 6-, or 7-positions are α or β; 
       the compounds are racemic or 1R- or 1S-configured; 
       X═O, NR 3 , NR 10 , CHR 3 , CHR 1 , CH 2 , CHW 1 , CW 1 W 1 , CO, S, SO, SO 2 , NSO 2 R 3 , NSO 2 R 11  or CX 2 W, with the N, C, O or S atom being a member of the ring; 
       Ar=Phenyl or 1-naphthyl or 2-naphthyl, unsubstituted or substituted with one or more group selected from: —H; —Br; —Cl; —I; —F; —OH; —CH 3 ; —OCH 3 ; —CF 3 ; —NO 2 ; —NH 2 ; —CN; —NHCOCH 3 , —C(CH 3 ) 3 , —C(CH 2 )CH 3 , (CH 2 ) q CH 3 , where q=0-6; —COCH 3 ; OAc; alkyl; alkenyl; alkynyl; allyl; isopropyl; isobutyl; wherein each substitutent can be at the 2, 3 and/or 4 position of the ring; 
       W or X 2 ═H, OH, OCH 3 , OAc, OCOR 4 , CH 3 , (CH 2 ) n CH 3 , R 4 ; 
       W 1 ═H, Br, Cl, I, F, OH, OCH 3 , CF 3 , NO 2 , NH 2 , CN, NHCOCH 3 , N(CH 3 ) 2 , (CH 2 ) n CH 3 , COCH 3 , or C(CH 3 ) 3 ; 
       R 2 ═R 3 , OR 3 , isopropyl, isobutyl, OCOR 4 , OCOR 5 , W 1 , CH 2 R 3 , OCOR 3 , NHR 3 , COR 3 , (CH 2 ) n COOR 3 ; 
       R 3 ═H, CH 3 , CH 2 Ar, (CH 2 ) n Ar, Ar, alkyl, alkenyl or alkynyl, cycloalkylmethyl, CH 2 CH═CHZ, (CH 2 ) n OH, (CH 2 ) n OR 4 , CH═CHZ; CH 2 J-Maleimide, CH 2 JN-Maleimide where J=CH 2  or O; (CH 2 ) n OCOCH 3 ; (CH 2 ) n OCOCH 2 OCH 3 ; (CH 2 ) n -morpholine; (CH 2 ) n -piperidine; (CH 2 ) n -piperazine; 
       R 4 ═CH 3 , CH 2 CH 3 , alkyl, alkenyl, alkynyl, allyl, isopropyl, isobutyl; 
       R 5 ═H, CH 3 , (CH 3 ) 2 , (CH 2 ) n SO 3 Q, alkyl, (alkyl) 2 , alkenyl, alkynyl, Ar, OCH 3 ; 
       Q=K + , Na + , Li + , Ca 2+ , NH 4   + , RNH 3   + , or other pharmaceutically acceptable salts; 
       R 10 ═COR 4 , CH 2 OH, (CH 2 ) n OH, (CH 2 ) n OR 4 , (CH 2 ) n COOR 3 , (CH 2 ) n OCOR 3 ; 
       R 11 ═H, COOCH 3 , COOR 4 , COR 4 , CH 2 OH, (CH 2 ) n OH, (CH 2 ) n OR 4 , CR 3 ═NOR 3 , CH═NR 3 ; 
       R 6  and R 7  independently ═H, CH 3 , CH 2 CH 3 , (CH 2 ) r CH 3 , (CH 2 ) r Ar, isopropyl, isobutyl, CH═CH—(CH 2 ) r CH 3 , CH 2 CH═CH—(CH 2 ) r CH 3 , (CH 2 ) s CH═CH—(CH 2 ) r CH 3 , C≡C—(CH 2 ) r CH 3 , CH 2 C≡C—(CH 2 ) r CH 3 , (CH 2 ) s C≡C—(CH 2 ) r CH 3 , OCOR 3 , (CH 2 ) d OCOR 3 , COOR 3  or (CH 2 ) d COOR 3 ;
 d=1-6; 
 r=0-4; 
 s=0-4; 
 m=0-4; 
 n=0-4; and 
 
       Z=F, Cl, I or Br. 
     
   
   
       13 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to  claim 12 . 
   
   
       14 . (canceled) 
   
   
       15 . A method of treating a medical condition comprising administering to a patient a compound according to  claim 12  said medical condition being attention deficit hyperactivity disorder (ADHD), Parkinson's disease, cocaine addiction, smoking cessation, weight reduction, obsessive-compulsive disorder, various forms of depression, traumatic brain injury, stroke or narcolepsy. 
   
   
       16 . (canceled) 
   
   
       17 . A method of treating a medical condition comprising administering to a patient a compound according to  claim 12 , said medical condition being attention deficit hyperactivity disorder (ADHD); Parkinson's disease; cocaine addiction; smoking cessation;
 weight reduction; obsessive-compulsive disorder; various forms of depression; traumatic brain injury; stroke; narcolepsy; seasonal affective disorders; sexual dysfunction; sexual behavior disorders; learning deficit; disorders involving the release of acetylcholine, including memory deficits, senile dementia, dementia of aging, AIDS-dementia, pseudodementia, presenile dementia, autism, mutism, cognitive disorders, dyslexia, tardive dyskinesia, hyperkinesias, anxiety, panic disorders, paranoia, post-traumatic syndrome; social phobia, other phobias; psychosis; bipolar disorder and other psychiatric or clinical dysfunctions; mania; manic depression; schizophrenia (deficient form and productive form); acute or chronic extrapyramidal symptoms induced by neuroleptic agents; chronic fatigue syndrome; deficits of alertness, attention, arousal and vigilance; disorders of sleep and jet-lag; obesity, bulimia, anorexia nervosa and other eating disorders; cocaine and other drug addiction or misuse; alcoholism; neurological disorders; epilepsy; neurodegenerative diseases including Alzheimer Disease, Huntington Disease, Amyotrophic Lateral Sclerosis, Gilles de la Tourette syndrome; mild, moderate or severe pain of acute, chronic or recurrent character, pain caused by migraine, postoperative pain or phantom limb pain; disorders linked to decreased transmission of serotonin in mammals, including Ganser syndrome, migraine headache, pre-menstrual syndrome or late luteal phase syndrome or peripheral neuropathy.   
   
   
       18 . (canceled) 
   
   
       19 . A method of diagnosing a disease or disorder that affects monoamine transport comprising labeling a compound as described herein, comprising labeling a compound of  claim 12 , administering the labeled compound to a patient, imaging the binding of the labeled compound in the patient and comparing said imaged patient binding to a reference standard. 
   
   
       20 .- 22 . (canceled) 
   
   
       23 . A compound having the formula: 
     
       
         
         
             
             
         
       
       Where: 
       the 2-, 3-, 6-, or 7-positions are α or β; 
       the compounds are racemic or 1R- or 1S-configured; 
       X═O, NR 3 , NR 10 , CHR 3 , CHR 1 , CH 2 , CHW 1 , CW 1 W 1 , CO, S, SO, SO 2 , NSO 2 R 3 , NSO 2 R 11  or CX 2 W, with the N, C, O or S atom being a member of the ring; 
       Ar=Phenyl or 1-naphthyl or 2-naphthyl, unsubstituted or substituted with one or more group selected from: —H; —Br; —Cl; —I; —F; —OH; —CH 3 ; —OCH 3 ; —CF 3 ; —NO 2 ; —NH 2 ; —CN; —NHCOCH 3 , —C(CH 3 ) 3 , —C(CH 2 )CH 3 , (CH 2 ) q CH 3 , where q=0-6; —COCH 3 ; OAc; alkyl; alkenyl; alkynyl; allyl; isopropyl; isobutyl; wherein each substitutent can be at the 2, 3 and/or 4 position of the ring; 
       W or X 2 ═H, OH, OCH 3 , OAc, OCOR 4 , CH 3 , (CH 2 ) n CH 3 , R 4 ; 
       W 1 ═H, Br, Cl, I, F, OH, OCH 3 , CF 3 , NO 2 , NH 2 , CN, NHCOCH 3 , N(CH 3 ) 2 , (CH 2 ) n CH 3 , COCH 3 , or C(CH 3 ) 3 ; 
       R 3 ═H, CH 3 , CH 2 Ar, (CH 2 ) n Ar, Ar, alkyl, alkenyl or alkynyl, cycloalkylmethyl, CH 2 CH═CHZ, (CH 2 ) n OH, (CH 2 ) n OR 4 , CH═CHZ; CH 2 J-Maleimide, CH 2 JN-Maleimide where J=CH 2  or O; (CH 2 ) n OCOCH 3 ; (CH 2 ) n OCOCH 2 OCH 3 ; (CH 2 ) n -morpholine; (CH 2 ) n -piperidine; (CH 2 ) n -piperazine; 
       R 4 ═CH 3 , CH 2 CH 3 , alkyl, alkenyl, alkynyl, allyl, isopropyl, isobutyl; 
       R 5 ═H, CH 3 , (CH 3 ) 2 , (CH 2 ) n SO 3 Q, alkyl, (alkyl) 2 , alkenyl, alkynyl, Ar, OCH 3 ; 
       Q=K + , Na + , Li + , Ca 2+ , NH 4   + , RNH 3   + , or other pharmaceutically acceptable salts; 
       R 10 ═COR 4 , CH 2 OH, (CH 2 ) n OH, (CH 2 ) n OR 4 , (CH 2 ) n COOR 3 , (CH 2 ) n OCOR 3 ; 
       R 2 ═R 3 , OR 3 , isopropyl, isobutyl, OCOR 4 , OCOR 5 , W 1 , CH 2 R 3 , OCOR 3 , NHR 3 , COR 3 , (CH 2 ) n COOR 3 ; 
       R 1 ═H, (CH 2 ) n OH, (CH 2 ) n OR 4 , CR 3 ═NOR 3 , CH═NR 3 ; COOR 8 , COR 8 , CONHR 8 , CONR 8 R 8 , CH 2 CH 3 , (CH 2 ) n CH 3 , CHCHR 9 , (CH 2 ) n CCR 9 , (CH 2 ) n COOR 8 , (CH 2 ) n OCOR 8 , OCOR 8 , C 3 HNOR 9  or C 2 N 2 OR 9 ; 
       R 8 ═R 3 , Br, Cl, I, F, OH, OCH 3 , CF 3 , NO 2 , NH 2 , CN, NHCOCH 3 , N(CH 3 ) 2 , (CH 2 ) n CH 3 , COCH 3 , or C(CH 3 ) 3 ; C(CH 3 ) 3 , C 10 H 7  or C 10 H 6 W 1 ; 
       R 9 ═COOR 8 , CH 3 , (CH 2 ) n CH 3 , C 6 H 5 , C 6 H 4 Y, C 10 H 7  or C 10 H 6 W 1 ; 
       n=0-4; 
       m=0-4; and 
       Z=F, Cl, I or Br;
 wherein at least one of X, R 2  or R 1  comprises a COOR 3  group or a OCOR 3  group and wherein R 3  comprises an alkyl, cycloalkylmethyl, alkenyl or alkynyl group having from about 10 to 20 carbon atoms. 
 
     
   
   
       24 . The compound of  claim 23 , wherein the R 2  substituent comprises the R 3  alkyl, cycloalkylmethyl, alkenyl or alkynyl group having from 10 to 20 carbon atoms. 
   
   
       25 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to  claim 23 . 
   
   
       26 . (canceled) 
   
   
       27 . A method of treating a medical condition comprising administering to a patient a compound according to  claim 23  said medical condition being attention deficit hyperactivity disorder (ADHD), Parkinson's disease, cocaine addiction, smoking cessation, weight reduction, obsessive-compulsive disorder, various forms of depression, traumatic brain injury, stroke or narcolepsy. 
   
   
       28 . (canceled) 
   
   
       29 . A method of treating a medical condition comprising administering to a patient a compound according to  claim 23 , said medical condition being attention deficit hyperactivity disorder (ADHD); Parkinson's disease; cocaine addiction; smoking cessation; weight reduction; obsessive-compulsive disorder; various forms of depression; traumatic brain injury; stroke; narcolepsy; seasonal affective disorders; sexual dysfunction; sexual behavior disorders; learning deficit; disorders involving the release of acetylcholine, including memory deficits, senile dementia, dementia of aging, AIDS-dementia, pseudodementia, presenile dementia, autism, mutism, cognitive disorders, dyslexia, tardive dyskinesia, hyperkinesias, anxiety, panic disorders, paranoia, post-traumatic syndrome; social phobia, other phobias; psychosis; bipolar disorder and other psychiatric or clinical dysfunctions; mania; manic depression; schizophrenia (deficient form and productive form); acute or chronic extrapyramidal symptoms induced by neuroleptic agents; chronic fatigue syndrome; deficits of alertness, attention, arousal and vigilance; disorders of sleep and jet-lag; obesity, bulimia, anorexia nervosa and other eating disorders; cocaine and other drug addiction or misuse; alcoholism; neurological disorders; epilepsy; neurodegenerative diseases including Alzheimer Disease, Huntington Disease, Amyotrophic Lateral Sclerosis, Gilles de la Tourette syndrome; mild, moderate or severe pain of acute, chronic or recurrent character, pain caused by migraine, postoperative pain or phantom limb pain; disorders linked to decreased transmission of serotonin in mammals, including Ganser syndrome, migraine headache, pre-menstrual syndrome or late luteal phase syndrome or peripheral neuropathy. 
   
   
       30 . (canceled) 
   
   
       31 . A method of diagnosing a disease or disorder that affects monoamine transport comprising labeling a compound of  claim 23 , administering the labeled compound to a patient, imaging the binding of the labeled compound in the patient, and comparing said imaged patient binding to a reference standard. 
   
   
       32 . (canceled) 
   
   
       33 . (canceled) 
   
   
       34 . The method of  claim 31  in which the disease or disorder is attention deficit hyperactivity disorder (ADHD); Parkinson's disease; cocaine addiction; smoking cessation; weight reduction; obsessive-compulsive disorder; various forms of depression; traumatic brain injury; stroke; narcolepsy; seasonal affective disorders; sexual dysfunction; sexual behavior disorders; learning deficit; disorders involving the release of acetylcholine, including memory deficits, senile dementia, dementia of aging, AIDS-dementia, pseudodementia, presenile dementia, autism, mutism, cognitive disorders, dyslexia, tardive dyskinesia, hyperkinesias, anxiety, panic disorders, paranoia, post-traumatic syndrome; social phobia, other phobias; psychosis; bipolar disorder and other psychiatric or clinical dysfunctions; mania; manic depression; schizophrenia (deficient form and productive form); acute or chronic extrapyramidal symptoms induced by neuroleptic agents; chronic fatigue syndrome; deficits of alertness, attention, arousal and vigilance; disorders of sleep and jet-lag; obesity, bulimia, anorexia nervosa and other eating disorders; cocaine and other drug addiction or misuse; alcoholism; neurological disorders; epilepsy; neurodegenerative diseases including Alzheimer Disease, Huntington Disease, Amyotrophic Lateral Sclerosis, Gilles de la Tourette syndrome; mild, moderate or severe pain of acute, chronic or recurrent character, pain caused by migraine, postoperative pain or phantom limb pain; disorders linked to decreased transmission of serotonin in mammals, including Ganser syndrome, migraine headache, pre-menstrual syndrome or late luteal phase syndrome or peripheral neuropathy. 
   
   
       35 . The compound according to  claim 1 , wherein X further comprises N-L-Ch, where “L” is a linking moiety comprising a chain of atoms containing 2 to about 6 carbon atoms and “Ch” is a tridentate or tetradentate chelating ligand that forms a neutral complex with technetium or rhenium. 
   
   
       36 . The compound according to  claim 35  wherein “Ch” comprises N-{2-((2-((triphenylmethyl)thio)-ethyl)amino)acetyl}-S-(triphenylmethyl)-2-aminoethanethiol (“MAMA′”). 
   
   
       37 . The compound according to  claim 36  wherein the linker comprises (CH 2 ) m , CH 2 (CH 2 ) m CH 2 , (CH 2 ) m C 6 H 4 (CH 2 ) p , CH 2 (CHCH)CH 2 , CH 2 CCCH 2 , (CH 2 ) m NHR(CH 2 ), (CH 2 ) m O(CH 2 ), (CH 2 ) m S(CH 2 ), CH 2 CONH(CH 2 ) m , (CH 2 ) m CONH(CH 2 ) p , and (CH 2 ) m COO(CH 2 ) p , where m=0-5, p=0-5, and (m+p)=1-5. 
   
   
       38 . The compound according to  claim 23 , wherein X further comprises N-L-Ch, where “L” is a linking moiety comprising a chain of atoms containing 2 to about 6 carbon atoms and “Ch” is a tridentate or tetradentate chelating ligand that forms a neutral complex with technetium or rhenium. 
   
   
       39 . The compound according to  claim 38  wherein “Ch” comprises N-{2-((2-((triphenylmethyl)thio)-ethyl)amino)acetyl}-S-(triphenylmethyl)-2-aminoethanethiol (“MAMA′”). 
   
   
       40 . The compound according to  claim 38  wherein the linker comprises (CH 2 ) m , CH 2 (CH 2 ) m CH 2 , (CH 2 ) m C 6 H 4 (CH 2 ) p , CH 2 (CHCH)CH 2 , CH 2 CCCH 2 , (CH 2 ) m NHR(CH 2 ), (CH 2 ) m O(CH 2 ), (CH 2 ) m S(CH 2 ), CH 2 CONH(CH 2 ) m , (CH 2 ) m CONH(CH 2 ) p , and (CH 2 ) m COO(CH 2 ) p , where m=0-5, p=0-5, and (m+p)=1-5. 
   
   
       41 . A compound selected from the group consisting of 2-[{3-[3α-(4-Fluoro-phenyl)-2β-(1-methoxyimino-propyl)-8-aza-bicyclo[3.2.1]oct-8-yl]-propyl}-(2-tritylsulfanyl-ethyl)-amino]-N-(2-tritylsulfanyl-ethyl)-acetamide; 
     2-[{3-[3α-(3,4-Dichloro-phenyl)-2β-(1-methoxyimino-propyl)-8-aza-bicyclo[3.2.1]oct-8-yl]-propyl}-(2-tritylsulfanyl-ethyl)-amino]-N-(2-tritylsulfanyl-ethyl)-acetamide; 
     2-[{3-[2β-(1-Methoxyimino-propyl)-3α-naphthalen-2-yl-8-aza-bicyclo[3.2.1]oct-8-yl]-propyl}-(2-tritylsulfanyl-ethyl)-amino]-N-(2-tritylsulfanyl-ethyl)-acetamide; 
     2-[{3-[3β-(4-Fluoro-phenyl)-2β-(1-methoxyimino-propyl)-8-aza-bicyclo[3.2.1]oct-8-yl]-propyl}-(2-tritylsulfanyl-ethyl)-amino]-N-(2-tritylsulfanyl-ethyl)-acetamide; 
     2-[{3-[3β-(3,4-Dichloro-phenyl)-2β-(1-methoxyimino-propyl)-8-aza-bicyclo[3.2.1]oct-8-yl]-propyl}-(2-tritylsulfanyl-ethyl)-amino]-N-(2-tritylsulfanyl-ethyl)-acetamide; 
     2-[{3-[2β-(1-Methoxyimino-propyl)-3β-naphthalen-2-yl-8-aza-bicyclo[3.2.1]oct-8-yl]-propyl}-(2-tritylsulfanyl-ethyl)-amino]-N-(2-tritylsulfanyl-ethyl)-acetamide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3α-(4-fluorophenyl)tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3α-(3,4-dichlorophenyl)tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3α-(2-naphthyl)tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3β-(4-fluorophenyl)tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3β-(3,4-dichlorophenyl)tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3β-(2-naphthyl)tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide;(RS)—N-{2((3′N′-prolyl-(1″R-3α-(4-fluorophenyl)-7β-hydroxy-tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3α-(3,4-dichlorophenyl)-7β-hydroxy-tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3α-(2-naphthyl)-7β-hydroxy-tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3α-(4-fluorophenyl)-7β-dodecanoyloxy-tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3α-(3,4-dichlorophenyl)-7β-dodecanoyloxy-tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     (RS)—N-{2((3′N′-propyl-(1″R-3α-(2-naphthyl)-7β-dodecanoyloxy-tropane-2″β-(1-methoxyimino-propyl))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato} 99m technetium(V) oxide; 
     1-[3β-(4-Fluoro-phenyl)-8-(3-iodo-allyl)-8-aza-bicyclo[3.2.1]oct-2β-yl]-propan-1-one O-methyl-oxime; 
     1-[3β-(4-Fluoro-phenyl)-7β-hydroxy-8-(3-iodo-allyl)-8-aza-bicyclo[3.2.1]oct-2′-yl]-propan-1-one O-methyl-oxime;
 dodecanoic acid 3β-(4-fluoro-phenyl)-8-(3-iodo-allyl)-4β-(1-methoxyimino-propyl)-8-aza-bicyclo[3.2.1]oct-6β-yl ester; and 
 dodecanoic acid 3β-(4-fluoro-phenyl)-8-(3-iodo-allyl)-2β-(1-methoxyimino-propyl)-8-aza-bicyclo[3.2.1]oct-6β-yl ester. 
 
   
   
       42 .- 44 . (canceled)