(5R)-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione and method of preparation thereof
OwnerRobert McCall, Martin Meglasson +4inventors
InventorsRobert McCall, Martin Meglasson, Brad Acker, Richard Heier, Alan Jin, Malcolm Moon
Life of this patent
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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. The present invention also provides a novel pharmaceutical agent, (5R)-5 -(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione and pharmaceutically acceptable salts thereof.
Claims110
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
- R1, R2 and R3 are the same or different and are:
- —H,
- C1-C6 alkyl,
- C3-C5 alkenyl,
- C3-C5 alkynyl,
- C3-C5 cycloalkyl,
- C4-C10 cycloalkyl,
- phenyl substituted C1-C6 alkyl,
- —NR1R2 where R1 and R2 are cyclized with the attached nitrogen atom to produce pyrrolidiyl, piperidinyl, morphoninyl, 4-methyl piperazinyl or imidazolyl;
- X is:
- —H,
- C1-C6 alkyl,
- —F, —Cl, —Br, —I,
- —OH,
- C1-C6 alkoxy,
- cyano,
- carboxamide,
- carboxyl,
- (C1-C6 alkoxy)carbonyl,
- A is:
- CH,
- CH2,
- CH-(halogen) where halogen is —F, —Cl, —Br, —I,
- CHCH3,
- C═O,
- C═S,
- C—SCH3,
- C═NH,
- C—NH2,
- C—NHCH3,
- C—NHCOOCH3,
- C—NHCN,
- SO2,
- N;
- B is:
- CH2,
- CH,
- CH-(halogen) where halogen is as defined above,
- C═O,
- N,
- NH,
- N—CH3,
- D is:
- CH,
- CH2,
- CH-(halogen) where halogen is as defined above,
- C═O,
- O,
- N,
- NH,
- N—CH3;
- 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 CH2, CH-(halogen) where halogen is as defined above, CHCH3, C═O, C═S, C═NH, SO2;
- then D is CH2, CH-(halogen) where halogen is as defined above, C═O, O, NH, N—CH3;
- (2) that when n is 0, and
- A is CH, C—SCH3, C—NH2, C—NHCH3, C—NHCOOCH3, C—NHCN, N;
- then
- D is CH, N;
- (3) that when n is 1, and
- A is CH2, CH-(halogen) where halogen is as defined above, CHCH3, C═O, C═S, C═NH, SO2;
- and
- B is CH2, CH-(halogen) where halogen is as defined above, C═O, NH, N—CH3;
- then
- D is CH2, C═O, O, NH, N—CH3;
- (4) that when n is 1, and
- A is CH, C—SCH3, C—NH2, C—NHCH3, C—NHCOOCH3, C—NHCN, N;
- and
- B is CH, N;
- then
- D is CH2, C═O, O, NH, N—CH3;
- (5) that when n is 1, and
- A is CH2, CHCH3, C═O, C═S, C═NH, SO2, and
- B is CH, N;
- then
- D is CH, N;
- and pharmaceutically acceptable salts thereof to the human.
A method of inducing mating a non-human mammal which comprises administering a sexually mating amount of a compound of the formula (A)
- where
- R1, R2 and R3 are the same or different and are:
- —H,
- C1-C6 alkyl,
- C3-C5 alkenyl,
- C3-C5 alkynyl,
- C3-C5 cycloalkyl,
- C4-C10 cycloalkyl,
- phenyl substituted C1-C6 alkyl,
- —NR1R2 where R1 and R2 are cyclized with the attached nitrogen atom to produce pyrrolidiyl, piperidinyl, morphoninyl, 4-methyl piperazinyl or imidazolyl;
- X is:
- —H,
- C1-C6 alkyl,
- —F, —Cl, —Br, —I,
- —OH,
- C1-C6 alkoxy,
- cyano,
- carboxamide,
- carboxyl,
- (C1-C6 alkoxy)carbonyl,
- A is:
- CH,
- CH2,
- CH-(halogen) where halogen is —F, —Cl, —Br, —I,
- CHCH3,
- C═O,
- C═S,
- C—SCH3,
- C═NH,
- C—NH2,
- C—NHCH3,
- C—NHCOOCH3,
- C—NHCN,
- SO2,
- N;
- B is:
- CH2,
- CH,
- CH-(halogen) where halogen is as defined above,
- C═O,
- N,
- NH,
- N—CH3,
- D is:
- CH,
- CH2,
- CH-(halogen) where halogen is as defined above,
- C═O,
- O,
- N,
- NH,
- N—CH3;
- 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 CH2, CH-(halogen) where halogen is as defined above, CHCH3, C═O, C═S, C═NH, SO2;
- then D is CH2, CH-(halogen) where halogen is as defined above, C═O, O, NH, N—CH3;
- (2) that when n is 0, and
- A is CH, C—SCH3, C—NH2, C—NCH3, C—NCOOCH3, C—NHCN, N;
- then
- D is CH, N;
- (3) that when n is 1, and
- A is CH2, CH-(halogen) where halogen is as defined above, CHCH3, C═O, C═S, C═NH, SO2;
- and
- B is CH2, CH-(halogen) where halogen is as defined above, C═O, NH, N—CH3;
- then
- D is CH2, C═O, O, NH, N—CH3;
- (4) that when n is 1, and
- A is CH, C—SCH3, C—NH2, C—NHCH3, C—NHCOOCH3, C—NHCN, N;
- and
- B is CH, N;
- then
- D is CH2, C═O, O, NH, N—CH3;
- (5) that when n is 1, and
- A is CH2, CHCH3, C═O, C═S, C═NH, SO2, and
- B is CH, N;
- then
- D is CH, N;
- and pharmaceutically acceptable salts thereof.
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
- R1, R2 and R3 are the same or different and are:
- —H,
- C1-C6 alkyl,
- C3-C5 alkenyl,
- C3-C5 alkynyl,
- C3-C5 cycloalkyl,
- C4-C10 cycloalkyl,
- phenyl substituted C1-C6 alkyl,
- —NR1R2 where R1 and R2 are cyclized with the attached nitrogen atom to produce pyrrolidiyl, piperidinyl, morphoninyl, 4-methyl piperazinyl or imidazolyl;
- X is:
- —H,
- C1-C6 alkyl,
- —F, —Cl, —Br, —I,
- —OH,
- C1-C6 alkoxy,
- cyano,
- carboxamide,
- carboxyl,
- (C1-C6 alkoxy)carbonyl,
- A is:
- CH,
- CH2,
- CH-(halogen) where halogen is —F, —Cl, —Br, —I,
- CHCH3,
- C═O,
- C═S,
- C—SCH3,
- C═NH,
- C—NH2,
- C—NHCH3,
- C—NHCOOCH3,
- C—NHCN,
- SO2,
- N;
- B is:
- CH2,
- CH,
- CH-(halogen) where halogen is as defined above,
- C═O,
- N,
- NH,
- N—CH3,
- D is:
- CH,
- CH2,
- CH-(halogen) where halogen is as defined above,
- C═O,
- O,
- N,
- NH,
- N—CH3;
- 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 CH2, CH-(halogen) where halogen is as defined above, CHCH3, C═O, C═S, C═NH, SO2;
- then D is CH2, CH-(halogen) where halogen is as defined above, C═O, O, NH, N—CH3;
- (2) that when n is 0, and
- A is CH, C—SCH3, C—NH2, C—NHCH3, C—NHCOOCH3, C—NHCN, N;
- then
- D is CH, N;
- (3) that when n is 1, and
- A is CH2, CH-(halogen) where halogen is as defined above, CHCH3, C═O, C═S, C═NH, SO2;
- and
- B is CH2, CH-(halogen) where halogen is as defined above, C═O, NH, N—CH3;
- then
- D is CH2, C═O, O, NH, N—CH3;
- (4) that when n is 1, and
- A is CH, C—SCH3, C—NH2, C—NHCH3, C—NHCOOCH3, C—NHCN, N;
- and
- B is CH, N;
- then
- D is CH2, C═O, O, NH, N—CH3;
- (5) that when n is 1, and
- A is CH2, CHCH3, C═O, C═S, C═NH, SO2, and
- B is CH, N;
- then
- D is CH, N;
- and pharmaceutically acceptable salts thereof to the human.
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 R1, R2 and R3 are the same or different and are:
- —H,
- C1-C6 alkyl,
- C3-C5 alkenyl,
- C3-C5 alkynyl,
- C3-C5 cycloalkyl,
- C4-C10 cycloalkyl,
- phenyl substituted C1-C6 alkyl,
- —NR1R2 where R1 and R2 are cyclized with the attached nitrogen atom to produce pyrrolidiyl, piperidinyl, morphoninyl, 4-methyl piperazinyl or imidazolyl;
- X is:
- —H,
- C1-C6 alkyl,
- —F, —Cl, —Br, —I,
- —OH,
- C1-C6 alkoxy,
- cyano,
- carboxamide,
- carboxyl,
- (C1-C6 alkoxy)carbonyl,
- A is:
- CH,
- CH2,
- CH-(halogen) where halogen is —F, —Cl, —Br, —I,
- CHCH3,
- C═O,
- C═S,
- C—SCH3,
- C═NH,
- C—NH2,
- C—NHCH3,
- C—NHCOOCH3,
- C—NHCN,
- SO2,
- N;
- B is:
- CH2,
- CH,
- CH-(halogen) where halogen is as defined above,
- C═O,
- N,
- NH,
- N—CH3,
- D is:
- CH,
- CH2,
- CH-(halogen) where halogen is as defined above,
- C═O,
- O,
- N,
- NH,
- N—CH3;
- 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 CH2, CH-(halogen) where halogen is as defined above, CHCH3, C═O, C═S, C═NH, SO2;
- then D is CH2, CH-(halogen) where halogen is as defined above, C═O, O, NH, N—CH3;
- (2) that when n is 0, and
- A is CH, C—SCH3, C—NH2, C—NHCH3, C—NHCOOCH3, C—NHCN, N;
- then
- D is CH, N;
- (3) that when n is 1, and
- A is CH2, CH-(halogen) where halogen is as defined above, CHCH3, C═O, C═S, C═NH, SO2;
- and
- B is CH2, CH-(halogen) where halogen is as defined above, C═O, NH, N—CH3;
- then
- D is CH2, C═O, O, NH, N—CH3;
- (4) that when n is 1, and
- A is CH, C—SCH3, C—NH2, C—NHCH3, C—NHCOOCH3, C—NHCN, N;
- and
- B is CH, N;
- then
- D is CH2, C═O, O, NH, N—CH3;
- (5) that when n is 1, and
- A is CH2, CHCH3, C═O, C═S, C═NH, SO2, and
- B is CH, N;
- then
- D is CH, N;
- and pharmaceutically acceptable salts thereof to the human.
(5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione and pharmaceutically acceptable salts thereof.
A compound of the formula
- and pharmaceutically acceptable salts thereof.
(5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione and pharmaceutically acceptable salts thereof.
A process for the preparation of (5R)-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione which comprises:
- (1) contacting (5R)-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-one or pharmaceutically acceptable salts thereof with tetraphosphorous decasulfide and
- (2) heating to more than 100°.
Dependencies are inferred from the claim text.