US2004214823A1PendingUtilityA1

Method of treating sexual disturbances

Assignee: UPJOHN COPriority: Jan 6, 1999Filed: May 14, 2004Published: Oct 28, 2004
Est. expiryJan 6, 2019(expired)· nominal 20-yr term from priority
A61P 9/08A61P 15/10A61P 15/00A61P 21/02A61K 31/485A61K 31/47A61K 31/4745A61K 31/535A61K 31/52A61K 38/2278A61K 31/475A61K 31/557
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Claims

Abstract

The present invention is a method of treating sexual disturbances in humans and inducing mating in non-human mammals using the compounds of formula (A) in a dosage range where the sexually therapeutic amount is from about 0.2 thru 8 mg/person/dose and where the sexually mating amount is from about 0.003 thru 0.2 mg/kg/dose.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method of treating sexual disturbances in a human who is in need of such treatment which comprises administering a sexually therapeutically effective amount of a compound of the formula (A)  
       
         
           
           
               
               
           
         
       
       where 
 R 1 , R 2  and R 3  are the same or different and are: 
 —H,  
 C 1 -C 6  alkyl,  
 C 3 -C 5  alkenyl,  
 C 3 -C 5  alkynyl,  
 C 3 -C 5  cycloalkyl,  
 C 4 -C 10  cycloalkyl,  
 phenyl substituted C 1 -C 6  alkyl,  
 —NR 1 R 2  where R 1  and R 2  are cyclized with the attached nitrogen atom to produce pyrrolidiyl, piperidinyl, morphoninyl, 4-methyl piperazinyl or imidazolyl;  
 
 X is: 
 —H,  
 C 1 -C 6  alkyl,  
 —F, —Cl, —Br, —I,  
 —OH,  
 C 1 -C 6  alkoxy,  
 cyano,  
 carboxamide,  
 carboxyl,  
 (C 1 -C 6  alkoxy)carbonyl,  
 
 A is: 
 CH,  
 CH 2 ,  
 CH-(halogen) where halogen is —F, —Cl, —Br, —I,  
 CHCH 3 ,  
 C═O,  
 C═S,  
 C—SCH 3 ,  
 C═NH,  
 C—NH 2 ,  
 C—NHCH 3 ,  
 C—NHCOOCH 3 ,  
 C—NHCN,  
 SO 2 ,  
 N;  
 
 B is: 
 CH 2 ,  
 CH,  
 CH-(halogen) where halogen is as defined above,  
 C═O,  
 N,  
 NH,  
 N—CH 3 ,  
 
 D is: 
 CH,  
 CH 2 ,  
 CH-(halogen) where halogen is as defined above,  
 C═O,  
 O,  
 N,  
 NH,  
 N—CH 3 :  
 and n is 0 or 1, and where  is a single or double bond, with the provisos:  
 
 (1) that when n is 0, and 
 A is CH 2 , CH-(halogen) where halogen is as defined above, CHCH 3 , C═O, C═S, C═NH, SO 2 ,  
 then D is CH 2 , CH-(halogen) where hallogen is as defined above, C═O, O, NH, N—CH 3 ;  
 
 (2) that when n is 0, and 
 A is CH, C—SCH 3 , C—NH 2 , C—NHCH 3 , C—NHCOOCH 3 , C—NHCN, N; then  
 D is CH, N;  
 
 (3) that when n is 1, and 
 A is CH 2 , CH-(halogen) where halogen is as defined above, CHCH 3 , C═O, C═S, C═NH, SO 2 ; and  
 B is CH 2 , CH-(halogen) where halogen is as defined above, C═O, NH, N—CH 3 ; then  
 D is CH 2 , C═O, O, NH, N—CH 3 ;  
 
 (4) that when n is 1, and 
 A is CH, C—SCH 3 , C—NH 2 , C—NHCH 3 , C—NHCOOCH 3 , C—NHCN, N; and  
 B is CH, N; then  
 D is CH 2 , C═O, O, NH, N—CH 3 ;  
 
 (5) that when n is 1, and 
 A is CH 2 , CHCH 3 , C═O, C═S, C═NH, SO 2 , and  
 B is CH, N; then  
 D is CH, N; and pharmaceutically acceptable salts thereof to the human.  
 
 
     
     
         2 . A method of treating sexual disturbances according to  claim 1  where the compound of formula (A) is (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione.  
     
     
         3 . A method of inducing mating a non-human mammal which comprises administering a sexually mating amount of a compound of the formula (A)  
       
         
           
           
               
               
           
         
       
       where 
 R 1 , R 2  and R 3  are the same or different and are: 
 —H,  
 C 1 -C 6  alkyl,  
 C 3 -C 5  alkenyl,  
 C 3 -C 5  alkynyl,  
 C 3 -C 5  cycloalkyl,  
 C 4 -C 10  cycloalkyl,  
 phenyl substituted C 1 -C 6  alkyl,  
 —NR 1 R 2  where R 1  and R 2  are cyclized with the attached nitrogen atom to produce pyrrolidiyl, piperidinyl, morphoninyl, 4-methyl piperazinyl or imidazolyl;  
 
 X is: 
 —H,  
 C 1 -C 6  alkyl,  
 —F, —Cl, —Br, —I,  
 —OH,  
 C 1 -C 6  alkoxy,  
 cyano,  
 carboxamide,  
 carboxyl,  
 (C 1 -C 6  alkoxy)carbonyl,  
 
 A is: 
 CH,  
 CH 2 ,  
 CH-(halogen) where halogen is —F, —Cl, —Br, —I,  
 CHCH 3 ,  
 C═O,  
 C═S,  
 C—SCH 3 ,  
 C═NH,  
 C—NH 2 ,  
 C—NHCH 3 ,  
 C—NHCOOCH 3 ,  
 C—NHCN,  
 SO 2 ,  
 N;  
 
 B is: 
 CH 2 ,  
 CH,  
 CH-(halogen) where halogen is as defined above,  
 C═O,  
 N,  
 NH,  
 N—CH 3 ,  
 
 D is: 
 CH,  
 CH 2 ,  
 CH-(halogen) where halogen is as defined above,  
 C═O,  
 O,  
 N,  
 NH,  
 N—CH 3 ;  
 and n is 0 or 1, and where  is a single or double bond, with the provisos:  
 
 (1) that when n is 0, and 
 A is CH 2 , CH-(halogen) where halogen is as defined above, CHCH 3 , C═O, C═S, C═NH, SO 2 ;  
 then D is CH 2 , CH-(halogen) where halogen is as defined above, C═O, O, NH, N—CH 3 ;  
 
 (2) that when n is 0, and 
 A is CH, C—SCH 3 , C—NH 2 , C—NHCH 3 , C—NHCOOCH 3 , C—NHCN, N; then  
 D is CH, N;  
 
 (3) that when n is 1, and 
 A is CH 2 , CH-(halogen) where halogen is as defined above, CHCH 3 , C═O, C═S, C═NH, SO 2 ; and  
 B is CH 2 , CH-(halogen) where halogen is as defined above, C═O, NH, N—CH 3 ; then  
 D is CH 2 , C═O, O, NH, N—CH 3 ,  
 
 (4) that when n is 1, and 
 A is CH, C—SCH 3 , C—NH 2 , C—NHCH 3 , C—NHCOOCH 3 , C—NHCN, N; and  
 B is CH, N; then  
 D is CH 2 , C═O, O, NH, N—CH 3 ;  
 
 (5) that when n is 1, and 
 A is CH 2 , CHCH 3 , C═O, C═S, C═NH, SO 2 , and  
 B is CH, N; then  
 D is CH, N; and pharmaceutically acceptable salts thereof.  
 
 
     
     
         4 . A method of inducing mating according to  claim 3  where the compound of formula (A) is (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione.  
     
     
         5 . A method of treating a sexual deficiency state in a human who has epilepsy, craniopharyngioma, hypogonadism or who has had a hysterectomyoophorectomy, hysterectomy or oophorectomy which comprises administering a sexually therapeutically effective amount of a compound of the formula (A)  
       
         
           
           
               
               
           
         
       
       where 
 R 1 , R 2  and R 3  are the same or different and are: 
 —H,  
 C 1 -C 6  alkyl,  
 C 3 -C 5  alkenyl,  
 C 3 -C 5  alkynyl,  
 C 3 -C 5  cycloalkyl,  
 C 4 -C 10  cycloalkyl,  
 phenyl substituted C 1 -C 6  alkyl,  
 —NR 1 R 2  where R 1  and R 2  are cyclized with the attached nitrogen atom to produce pyrrolidiyl, piperidinyl, morphoninyl, 4-methyl piperazinyl or imidazolyl;  
 
 X is: 
 —H,  
 C 1 -C 6  alkyl,  
 —F, —Cl, —Br, —I,  
 —OH,  
 C 1 -C 6  alkoxy,  
 cyano,  
 carboxamide,  
 carboxyl,  
 (C 1 -C 6  alkoxy)carbonyl,  
 
 A is: 
 CH,  
 CH 2 ,  
 CH-(halogen) where halogen is —F, —Cl, —Br, —I,  
 CHCH 3 ,  
 C═O,  
 C═S,  
 C—SCH 3 ,  
 C═NH,  
 C—NH 2 ,  
 C—NHCH 3 ,  
 C—NHCOOCH 3 ,  
 C—NHCN,  
 SO 2 ,  
 N;  
 
 B is: 
 CH 2 ,  
 CH,  
 CH-(halogen) where halogen is as defined above,  
 C═O,  
 N,  
 NH,  
 N—CH 3 ,  
 
 D is: 
 CH,  
 CH 2 ,  
 CH-(halogen) where halogen is as defined above,  
 C═O,  
 O,  
 N,  
 NH,  
 N—CH 3 ;  
 and n is 0 or 1, and where  is a single or double bond, with the provisos:  
 
 (1) that when n is 0, and 
 A is CH 2 , CH-(halogen) where halogen is as defined above, CHCH 3 , C═O, C═S, C═NH, SO 2 ;  
 then D is CH 2 , CH-(halogen) where halogen is as defined above, C═O, O, NH, N—CH 3 ;  
 
 (2) that when n is 0, and 
 A is CH, C—SCH 3 , C—NH 2 , C—NHCH 3 , C—NHCOOCH 3 , C—NHCN, N; then  
 D is CH, N;  
 
 (3) that when n is 1, and 
 A is CH 2 , CH-(halogen) where halogen is as defined above, CHCH 3 , C═O, C═S, C═NH, SO 2 ; and  
 B is CH 2 , CH-(halogen) where halogen is as defined above, C═O, NH, N—CH 3 ; then  
 D is CH 2 , C═O, O, NH, N—CH 3 ;  
 
 (4) that when n is 1, and 
 A is CH, C—SCH 3 , C—NH 2 , C—NHCH 3 , C—NHCOOCH 3 , C—NHCN, N; and  
 B is CH, N; then  
 D is CH 2 , C═O, O, NH, N—CH 3 ,  
 
 (5) that when n is 1, and 
 A is CH 2 , CHCH 3 , C═O, C═S, C═NH, SO 2 , and  
 B is CH, N; then  
 D is CH, N; and pharmaceutically acceptable salts thereof to the human.  
 
 
     
     
         6 . A method of treating a sexual deficiency state according to  claim 5  where the compound of formula (A) is (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione.  
     
     
         7 . A method of increasing sexual desire, interest or performance in a human who is desirous thereof which comprises administering a sexually useful effective amount of a compound of the formula (A)  
       
         
           
           
               
               
           
         
       
       where 
 R 1 , R 2  and R 3  are the same or different and are: 
 —H,  
 C 1 -C 6  alkyl,  
 C 3 -C 5  alkenyl,  
 C 3 -C 5  alkynyl,  
 C 3 -C 5  cycloalkyl,  
 C 4 -C 10  cycloalkyl,  
 phenyl substituted C 1 -C 6  alkyl,  
 —NR 1 R 2  where R 1  and R 2  are cyclized with the attached nitrogen atom to produce pyrrolidiyl, piperidinyl, morphoninyl, 4-methyl piperazinyl or imidazolyl;  
 
 X is: 
 —H,  
 C 1 -C 6  alkyl,  
 —F, —Cl, —Br, —I,  
 —OH,  
 C 1 -C 6  alkoxy,  
 cyano,  
 carboxamide,  
 carboxyl,  
 (C 1 -C 6  alkoxy)carbonyl,  
 
 A is: 
 CH,  
 CH 2 ,  
 CH-(halogen) where halogen is —F, —Cl, —Br, —I,  
 CHCH 3 ,  
 C═O,  
 C═S,  
 C—SCH 3 ,  
 C═NH,  
 C—NH 2 ,  
 C—NHCH 3 ,  
 C—NHCOOCH 3 ,  
 C—NHCN,  
 SO 2 ,  
 N;  
 
 B is: 
 CH 2 ,  
 CH,  
 CH-(halogen) where halogen is as defined above,  
 C═O,  
 N,  
 NH,  
 N—CH 3 ,  
 
 D is: 
 CH,  
 CH 2 ,  
 CH-(halogen) where halogen is as defined above,  
 C═O,  
 O,  
 N,  
 NH,  
 N—CH 3 ;  
 and n is 0 or 1, and where  is a single or double bond, with the provisos:  
 
 (1) that when n is 0, and 
 A is CH 2 , CH-(halogen) where halogen is as defined above, CHCH 3 , C═O, C═S, C═NH, SO 2 ;  
 then D is CH 2 , CH-(halogen) where halogen is as defined above, C═O, O, NH, N—CH 3 ,  
 
 (2) that when n is 0, and 
 A is CH, C—SCH 3 , C—NH 2 , C—NHCH 3 , C—NHCOOCH 3 , C—NHCN, N; then  
 D is CH, N;  
 
 (3) that when n is 1, and 
 A is CH 2 , CH-(halogen) where halogen is as defined above, CHCH 3 , C═O, C═S, C═NH, SO 2 ; and  
 B is CH 2 , CH-(halogen) where halogen is as defined above, C═O, NH, N—CH 3 ; then  
 D is CH 2 , C═O, O, NH, N—CH 3 ;  
 
 (4) that when n is 1, and 
 A is CH, C—SCH 3 , C—NH 2 , C—NHCH 3 , C—NHCOOCH 3 , C—NHCN, N; and  
 B is CH, N; then  
 D is CH 2 , C═O, O, NH, N—CH 3 ;  
 
 (5) that when n is 1, and 
 A is CH 2 , CHCH 3 , C═O, C═S, C═NH, SO 2 , and  
 B is CH, N; then  
 D is CH, N; and pharmaceutically acceptable salts thereof to the human.  
 
 
     
     
         8 . A method of increasing sexual desire, interest or performance in a human who is desirous thereof according to  claim 7  where the compound of formula (A) is (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione.  
     
     
         9 . (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione and pharmaceutically acceptable salts thereof.  
     
     
         10 . A compound according to  claim 9  which is (5R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione malate.

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