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US4440771A
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US
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2-Acetyl quinoline thiosemicarbazones useful in treatment of gonorrhea, malaria or bacterial infections
Assignee: United States Department of the Army
•
Filing: 1982-02-12
•
Granted: 1984-04-03
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Expires: 2002-02-12
Abstract
Abstract This invention relates to the preparation and use of various 2-acetyl quinoline thiosemicarbazones which are substituted on the 4-nitrogen atom. These compounds are useful in the treatment of gonorrhea and, in addition, many are useful either in the treatment of malaria or bacterial infections, such as leprosy and meningitis.
Inventors
- 👤 John P. Scovill
- 👤 Daniel L. Klayman
- 👤 Samuel P. Massie
- 👤 Steven D. Grant
- 👤 Armando Gonzalez
- 👤 Norman E. Morrison
- 👤 Arthur S. Dobek
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 10:34
CPC Classifications
C; C07; C07D; C07D401/00; C07D401/02; C07D401/12; C07D215/00; C07D215/02; C07D215/12; C07D215/14; Y; Y02; Y02A; Y02A50/00; Y02A50/30
Claims Analysis
Total Claims: 60
Claim 1
Independent Claim
399 words
A quinoline thiosemicarbazones compound of the formula ##STR14## or a pharmaceutically-acceptable acid addition salt thereof wherein R 1 is alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 10 carbon atoms; substituted alkyl of 1 to 12 carbon atoms (wherein the substituent is amino, alkylamino of 1 to 4 carbon atoms, dialkylamino of 1 to 4 carbon atoms in each alkyl group, cycloalkyl of 3 to 10 carbon atoms, hydroxy, COO alkyl of 1 to 4 carbon atoms, phenyl, or pyridyl); alkenyl of 2 to 6 carbon atoms; alkynyl of 3 to 6 carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of 1 to 4 carbon atoms, halo, alkoxy of 1 to 4 carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylamino, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: (1) alkylenimino having 3 to 13 carbon atoms; (2) alkylenimino having 3 to 13 carbon atoms which may contain one double bond and/or is mono- or disubstituted with alkyl having 1 to 4 carbon atoms, hydroxy, phenyl, or benzyl; (3) alkylenimino having 3 to 13 carbon atoms which is either bridged by an alkylene group having 1 to 3 carbon atoms, or is fused to a phenyl ring, or is attached by a spiro linkage to an ethylene ketal group; (4) homopiperazinyl; homopiperazinyl substituted with alkyl having 1 to 4 carbon atoms; piperazinyl; or piperazinyl substituted with alkyl having 1 to 4 carbon atoms, dialkyl having 1 to 4 carbon atoms in each alkyl group, phenyl, COO alkyl having 1 to 4 carbon atoms in the alkyl group, trifluoromethylphenyl, halophenyl, benzyl, or pyridyl; and (5) morpholino; dialkylmorpholino having 1 to 4 carbon atoms in each alkyl group; provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 2
Dependent Claim
399 words
A quinoline thiosemicarbazones compound of the formula ##STR14## or a pharmaceutically-acceptable acid addition salt thereof wherein R 1 is alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 10 carbon atoms; substituted alkyl of 1 to 12 carbon atoms (wherein the substituent is amino, alkylamino of 1 to 4 carbon atoms, dialkylamino of 1 to 4 carbon atoms in each alkyl group, cycloalkyl of 3 to 10 carbon atoms, hydroxy, COO alkyl of 1 to 4 carbon atoms, phenyl, or pyridyl); alkenyl of 2 to 6 carbon atoms; alkynyl of 3 to 6 carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of 1 to 4 carbon atoms, halo, alkoxy of 1 to 4 carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylamino, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: (1) alkylenimino having 3 to 13 carbon atoms; (2) alkylenimino having 3 to 13 carbon atoms which may contain one double bond and/or is mono- or disubstituted with alkyl having 1 to 4 carbon atoms, hydroxy, phenyl, or benzyl; (3) alkylenimino having 3 to 13 carbon atoms which is either bridged by an alkylene group having 1 to 3 carbon atoms, or is fused to a phenyl ring, or is attached by a spiro linkage to an ethylene ketal group; (4) homopiperazinyl; homopiperazinyl substituted with alkyl having 1 to 4 carbon atoms; piperazinyl; or piperazinyl substituted with alkyl having 1 to 4 carbon atoms, dialkyl having 1 to 4 carbon atoms in each alkyl group, phenyl, COO alkyl having 1 to 4 carbon atoms in the alkyl group, trifluoromethylphenyl, halophenyl, benzyl, or pyridyl; and (5) morpholino; dialkylmorpholino having 1 to 4 carbon atoms in each alkyl group; provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 3
Dependent Claim
302 words
A quinoline thiosemicarbazone compound of the formula ##STR15## or a pharmaceutically-acceptable acid addition salt thereof wherein R is methyl or ethyl; and R 1 is alkyl of one to 12 carbon atoms; cycloalkyl of three to ten carbon atoms; substituted alkyl of one to 12 carbon atoms (wherein the substituent is amino, alkylamino of one to four carbon atoms, dialkylamino wherein the alkyl groups each contain one to four carbon atoms, cycloalkyl of three to ten carbon atoms, hydroxy, COO alkyl wherein the alkyl group contains one to four atoms, phenyl, or pyridyl); alkenyl of two to six carbon atoms; alkynyl of three to six carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of one to four carbon atoms, halo, alkoxy of one to four carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylaminomethyl, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: azetidino; pyrrolidino; 2,5-dimethylpyrrolidino; piperidino; ##STR16## (wherein X is 2-methyl, 3-methyl, 4-methyl, 2-ethyl, 4-hydroxy, 4-phenyl, or 4benzyl); hexamethylenimino; octamethylenimino; dodecamethylenimino; 2,6-dimethyl piperidino; 3,5-dimethyl piperidino; morpholino; 3,5-dimethylmorpholino; ##STR17## (wherein Z is methyl, phenyl, 3-trifluoromethylphenyl, benzyl, COOEt, 3-pyridyl, 2-pyridyl, or 4-fluorophenyl); azacyclotridecyl; ##STR18## provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 4
Dependent Claim
302 words
A quinoline thiosemicarbazone compound of the formula ##STR15## or a pharmaceutically-acceptable acid addition salt thereof wherein R is methyl or ethyl; and R 1 is alkyl of one to 12 carbon atoms; cycloalkyl of three to ten carbon atoms; substituted alkyl of one to 12 carbon atoms (wherein the substituent is amino, alkylamino of one to four carbon atoms, dialkylamino wherein the alkyl groups each contain one to four carbon atoms, cycloalkyl of three to ten carbon atoms, hydroxy, COO alkyl wherein the alkyl group contains one to four atoms, phenyl, or pyridyl); alkenyl of two to six carbon atoms; alkynyl of three to six carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of one to four carbon atoms, halo, alkoxy of one to four carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylaminomethyl, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: azetidino; pyrrolidino; 2,5-dimethylpyrrolidino; piperidino; ##STR16## (wherein X is 2-methyl, 3-methyl, 4-methyl, 2-ethyl, 4-hydroxy, 4-phenyl, or 4benzyl); hexamethylenimino; octamethylenimino; dodecamethylenimino; 2,6-dimethyl piperidino; 3,5-dimethyl piperidino; morpholino; 3,5-dimethylmorpholino; ##STR17## (wherein Z is methyl, phenyl, 3-trifluoromethylphenyl, benzyl, COOEt, 3-pyridyl, 2-pyridyl, or 4-fluorophenyl); azacyclotridecyl; ##STR18## provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 5
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 1 R 2 is ##STR19##
Claim 6
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 2 R 2 is ##STR20##
Claim 7
Dependent Claim
20 words
A compound or salt of claim 1 wherein NR 1 R 2 is NHCH 2 CH 2 CH 3 .
Claim 8
Dependent Claim
22 words
A compound or salt of claim 1 wherein NR 1 R 2 is N(CH 2 CH(CH 3 ) 2 ) 2 .
Claim 9
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 1 R 2 is azetidino.
Claim 10
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 1 R 2 is piperidino.
Claim 11
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 1 R 2 is 2-methylpiperidino.
Claim 12
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 1 R 2 is ethylpiperidino.
Claim 13
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 1 R 2 is hexamethylenimino.
Claim 14
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 1 R 2 is azacyclotridecyl.
Claim 15
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 1 R 2 is ##STR21##
Claim 16
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 1 R 2 is ##STR22##
Claim 17
Dependent Claim
14 words
A compound or salt of claim 1 wherein NR 1 R 2 is ##STR23##
Claim 18
Dependent Claim
16 words
A compound or salt of claim 1 wherein R 1 and R 2 are each methyl.
Claim 19
Dependent Claim
17 words
A compound or salt of claim 1 wherein R 1 is 1-adamantyl and R 2 is hydrogen.
Claim 20
Dependent Claim
17 words
A compound or salt of claim 1 wherein R 1 is allyl and R 2 is hydrogen.
Claim 21
Dependent Claim
17 words
A compound or salt of claim 1 wherein R 1 is cyclohexyl and R 2 is hydrogen.
Claim 22
Dependent Claim
17 words
A compound or salt of claim 1 wherein R 1 is diethylaminoethyl and R 2 is hydrogen.
Claim 23
Dependent Claim
17 words
A compound or salt of claim 1 wherein R 1 is 3-fluorophenyl and R 2 is hydrogen.
Claim 24
Dependent Claim
16 words
A compound or salt of claim 1 wherein R 1 and R 2 are each isobutyl.
Claim 25
Dependent Claim
17 words
A compound or salt of claim 1 wherein R 1 is methyl and R 2 is cyclohexyl.
Claim 26
Dependent Claim
17 words
A compound or salt of claim 1 wherein R 1 is 2-methylbenzyl and R 2 is hydrogen.
Claim 27
Dependent Claim
17 words
A compound or salt of claim 1 wherein R 1 is 2-pyridyl and R 2 is hydrogen.
Claim 28
Dependent Claim
17 words
A compound or salt of claim 1 wherein R 1 is 1,1,3,3-tetramethylbutyl and R 2 is hydrogen.
Claim 29
Dependent Claim
17 words
A compound or salt of claim 1 wherein R 1 is 2-picolyl and R 2 is hydrogen.
Claim 30
Independent Claim
411 words
A method for treating an animal infected with leprosy by administering to said animal a therapeutically effective amount of a quinoline thiosemicarbazone compound of the formula ##STR24## or a pharmaceutically-acceptable acid addition salt thereof wherein R 1 is alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 10 carbon atoms; substituted alkyl of 1 to 12 carbon atoms (wherein the substituent is amino, alkylamino of 1 to 4 carbon atoms, dialkylamino of 1 to 4 atoms in each alkyl group, cycloalkyl of 3 to 10 carbon atoms, hydroxy, COO alkyl of 1 to 4 carbon atoms, phenyl, or pyridyl); alkenyl of 2 to 6 carbon atoms; alkynyl of 3 to 6 carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of 1 to 4 carbon atoms, halo, alkoxy of 1 to 4 carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylamino, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: (1) alkylenimino having 3 to 13 carbon atoms; (2) alkylenimino having 3 to 13 carbon atoms which may contain one double bond and/or is mono- or disubstituted with alkyl, hydroxy, phenyl, or benzyl; (3) alkylenimino having 3 to 13 carbon atoms which is either bridged by an alkylene group having 1 to 3 carbon atoms, or is fused to a phenyl ring, or is attached by a spiro linkage to an ethylene ketal group; (4) homopiperazinyl; homopiperazinyl substituted with alkyl having 1 to 4 carbon atoms; piperazinyl; or piperazinyl substituted with alkyl having 1 to 4 carbon atoms, dialkyl having 1 to 4 carbon atoms in each alkyl group, phenyl, COO alkyl having 1 to 4 carbon atoms in the alkyl group, trifluoromethylphenyl, halophenyl, benzyl, or pyridyl; and (5) morpholino; dialkylmorpholino having 1 to 4 carbon atoms in each alkyl group; provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 31
Independent Claim
411 words
A method for treating an animal infected with leprosy by administering to said animal a therapeutically effective amount of a quinoline thiosemicarbazone compound of the formula ##STR24## or a pharmaceutically-acceptable acid addition salt thereof wherein R 1 is alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 10 carbon atoms; substituted alkyl of 1 to 12 carbon atoms (wherein the substituent is amino, alkylamino of 1 to 4 carbon atoms, dialkylamino of 1 to 4 atoms in each alkyl group, cycloalkyl of 3 to 10 carbon atoms, hydroxy, COO alkyl of 1 to 4 carbon atoms, phenyl, or pyridyl); alkenyl of 2 to 6 carbon atoms; alkynyl of 3 to 6 carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of 1 to 4 carbon atoms, halo, alkoxy of 1 to 4 carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylamino, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: (1) alkylenimino having 3 to 13 carbon atoms; (2) alkylenimino having 3 to 13 carbon atoms which may contain one double bond and/or is mono- or disubstituted with alkyl, hydroxy, phenyl, or benzyl; (3) alkylenimino having 3 to 13 carbon atoms which is either bridged by an alkylene group having 1 to 3 carbon atoms, or is fused to a phenyl ring, or is attached by a spiro linkage to an ethylene ketal group; (4) homopiperazinyl; homopiperazinyl substituted with alkyl having 1 to 4 carbon atoms; piperazinyl; or piperazinyl substituted with alkyl having 1 to 4 carbon atoms, dialkyl having 1 to 4 carbon atoms in each alkyl group, phenyl, COO alkyl having 1 to 4 carbon atoms in the alkyl group, trifluoromethylphenyl, halophenyl, benzyl, or pyridyl; and (5) morpholino; dialkylmorpholino having 1 to 4 carbon atoms in each alkyl group; provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 32
Dependent Claim
14 words
The method of claim 28 wherein the quinoline thiosemicarbazone compound is 1-azacycloheptane-1-thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 33
Dependent Claim
14 words
The method of claim 28 wherein the quinoline thiosemicarbazone compound is 3-azabicyclo[3.2.2]nonane-3-thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 34
Dependent Claim
14 words
The method of claim 28 wherein the quinoline thiosemicarbazone compound is 4-(2-Pyridyl)piperidinothiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 35
Dependent Claim
14 words
The method of claim 28 wherein the quinoline thiosemicarbazone compound is Pyrrolidine-1-thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 36
Dependent Claim
15 words
The method of claim 28 wherein the quinoline thiosemicarbazone compound is 1-Propyl aminothiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 37
Dependent Claim
14 words
The method of claim 28 wherein the quinoline thiosemicarbazone compound is Diisobutylaminothiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 38
Independent Claim
419 words
A method for treating an animal having a malarial infection by administering to said animal a therapeutically effective amount of a quinoline thiosemicarbazone compound of the formula ##STR25## or a pharmaceutically-acceptable acid addition salt thereof wherein R 1 is alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 10 carbon atoms; substituted alkyl of 1 to 12 carbon atoms (wherein the substituent is amino, alkylamino of 1 to 4 carbon atoms, dialkylamino of 1 to 4 carbon atoms in each alkyl group, cycloalkyl of 3 to 10 carbon atoms, hydroxy, COO alkyl of 1 to 4 carbon atoms, phenyl, or pyridyl); alkenyl of 2 to 6 carbon atoms; alkynyl of 3 to 6 carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of 1 to 4 carbon atoms, halo, alkoxy of 1 to 4 carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylamino, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: (1) alkylenimino having 3 to 13 carbon atoms; (2) alkylenimino having 3 to 13 carbon atoms which may contain one double bond and/or is mono- or disubstituted with alkyl having 1 to 4 carbon atoms, hydroxy, phenyl, or benzyl; (3) alkylenimino having 3 to 13 carbon atoms which is either bridged by an alkylene group having 1 to 3 carbon atoms, or is fused to a phenyl ring, or is attached by a spiro linkage to an ethylene ketal group; (4) homopiperazinyl; homopiperazinyl substituted with alkyl having 1 to 4 carbon atoms; piperazinyl; or piperazinyl substituted with alkyl having 1 to 4 carbon atoms, dialkyl having 1 to 4 carbon atoms in each alkyl group, phenyl, COO alkyl having 1 to 4 carbon atoms in the alkyl group, trifluoromethylphenyl, halophenyl, benzyl, or pyridyl; and (5) morpholino; dialkylmorpholino having 1 to 4 carbon atoms in each alkyl group; provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 39
Independent Claim
419 words
A method for treating an animal having a malarial infection by administering to said animal a therapeutically effective amount of a quinoline thiosemicarbazone compound of the formula ##STR25## or a pharmaceutically-acceptable acid addition salt thereof wherein R 1 is alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 10 carbon atoms; substituted alkyl of 1 to 12 carbon atoms (wherein the substituent is amino, alkylamino of 1 to 4 carbon atoms, dialkylamino of 1 to 4 carbon atoms in each alkyl group, cycloalkyl of 3 to 10 carbon atoms, hydroxy, COO alkyl of 1 to 4 carbon atoms, phenyl, or pyridyl); alkenyl of 2 to 6 carbon atoms; alkynyl of 3 to 6 carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of 1 to 4 carbon atoms, halo, alkoxy of 1 to 4 carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylamino, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: (1) alkylenimino having 3 to 13 carbon atoms; (2) alkylenimino having 3 to 13 carbon atoms which may contain one double bond and/or is mono- or disubstituted with alkyl having 1 to 4 carbon atoms, hydroxy, phenyl, or benzyl; (3) alkylenimino having 3 to 13 carbon atoms which is either bridged by an alkylene group having 1 to 3 carbon atoms, or is fused to a phenyl ring, or is attached by a spiro linkage to an ethylene ketal group; (4) homopiperazinyl; homopiperazinyl substituted with alkyl having 1 to 4 carbon atoms; piperazinyl; or piperazinyl substituted with alkyl having 1 to 4 carbon atoms, dialkyl having 1 to 4 carbon atoms in each alkyl group, phenyl, COO alkyl having 1 to 4 carbon atoms in the alkyl group, trifluoromethylphenyl, halophenyl, benzyl, or pyridyl; and (5) morpholino; dialkylmorpholino having 1 to 4 carbon atoms in each alkyl group; provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 40
Dependent Claim
14 words
The method of claim 35 wherein the quinoline thiosemicarbazone compound is 1-Azacycloheptane-1-thiocarboxylic acid 2-[1-(2-quinolyl)ethlidene]hydrazide.
Claim 41
Dependent Claim
14 words
The method of claim 35 wherein the quinoline thiosemicarbazone compound is 3-Azabicyclo[3.2.2]nonane-3-thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazine.
Claim 42
Dependent Claim
14 words
The method of claim 35 wherein the quinoline thiosemicarbazone compound is Pyrrolidine-1-thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 43
Dependent Claim
14 words
The method of claim 35 wherein the quinoline thiosemicarbazone compound is 1-Propylaminothiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 44
Dependent Claim
15 words
The method of claim 35 wherein the quinoline thiosemicarbazone compound is Diisobutylamino thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 45
Independent Claim
408 words
A method for treating an animal infected with gonorrhoeae by administering to said animal a therapeutically effective amount of a quinoline thiosemicarbazone compound of the formula ##STR26## or a pharmaceutically-acceptable acid addition salt thereof wherein R 1 is alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 10 carbon atoms; substituted alkyl of 1 to 12 carbon atoms (wherein the substituent is amino, alkylamino, dialkylamino of 1 to 4 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, hydroxy, COO alkyl of 1 to 4 carbon atoms, phenyl, or pyridyl); alkenyl of 2 to 6 carbon atoms; alkynyl of 3 to 6 carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of 1 to 4 carbon atoms, halo, alkoxy of 1 to 4 carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylamino, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: (1) alkylenimino having 3 to 13 carbon atoms; (2) alkylenimino having 3 to 13 carbon atoms which may contain one double bond and/or is mono- or disubstituted with alkyl having 1 to 4 carbon atoms, hydroxy, phenyl, or benzyl; (3) alkylenimino having 3 to 13 carbon atoms which is either bridged by an alkylene group having 1 to 3 carbon atoms, or is fused to a phenyl ring, or is attached by a spiro linkage to an ethylene ketal group; (4) homopiperazinyl; homopiperazinyl substituted with alkyl having 1 to 4 carbon atoms; piperazinyl; or piperazinyl substituted with alkyl having 1 to 4 carbon atoms, dialkyl having 1 to 4 carbon atoms in each alkyl group, phenyl, COO alkyl having 1 to 4 carbon atoms in the alkyl group, trifluoromethylphenyl, halophenyl, benzyl, or pyridyl; and (5) morpholino; dialkylmorpholino having 1 to 4 carbon atoms in each alkyl group; provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 46
Independent Claim
408 words
A method for treating an animal infected with gonorrhoeae by administering to said animal a therapeutically effective amount of a quinoline thiosemicarbazone compound of the formula ##STR26## or a pharmaceutically-acceptable acid addition salt thereof wherein R 1 is alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 10 carbon atoms; substituted alkyl of 1 to 12 carbon atoms (wherein the substituent is amino, alkylamino, dialkylamino of 1 to 4 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, hydroxy, COO alkyl of 1 to 4 carbon atoms, phenyl, or pyridyl); alkenyl of 2 to 6 carbon atoms; alkynyl of 3 to 6 carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of 1 to 4 carbon atoms, halo, alkoxy of 1 to 4 carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylamino, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: (1) alkylenimino having 3 to 13 carbon atoms; (2) alkylenimino having 3 to 13 carbon atoms which may contain one double bond and/or is mono- or disubstituted with alkyl having 1 to 4 carbon atoms, hydroxy, phenyl, or benzyl; (3) alkylenimino having 3 to 13 carbon atoms which is either bridged by an alkylene group having 1 to 3 carbon atoms, or is fused to a phenyl ring, or is attached by a spiro linkage to an ethylene ketal group; (4) homopiperazinyl; homopiperazinyl substituted with alkyl having 1 to 4 carbon atoms; piperazinyl; or piperazinyl substituted with alkyl having 1 to 4 carbon atoms, dialkyl having 1 to 4 carbon atoms in each alkyl group, phenyl, COO alkyl having 1 to 4 carbon atoms in the alkyl group, trifluoromethylphenyl, halophenyl, benzyl, or pyridyl; and (5) morpholino; dialkylmorpholino having 1 to 4 carbon atoms in each alkyl group; provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 47
Dependent Claim
14 words
The method of claim 41 wherein the quinoline thiosemicarbazone compound is 1-Azacycloheptane-1-thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 48
Dependent Claim
14 words
The method of claim 41 wherein the quinoline thiosemicarbazone compound is 3-Azabicyclo[3.2.2]noname-3-thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 49
Dependent Claim
15 words
The method of claim 41 wherein the quinoline thiosemicarbazone compound is Diisobutylamino thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 50
Dependent Claim
14 words
The method of claim 41 wherein the quinoline thiosemicarbazone compound is Pyrrolidine-1-thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 51
Dependent Claim
14 words
The method of claim 41 wherein the quinoline thiosemicarbazone compound is 1-Propylaminothiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 52
Independent Claim
417 words
A method for treating an animal infected with meningitis by administering to said animal a therapeutically effective amount of a quinoline thiosemicarbazone compound of the formula ##STR27## or a pharmaceutically-acceptable acid addition salt thereof wherein R.sub. is alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 10 carbon atoms; substituted alkyl of 1 to 12 carbon atoms (wherein the substituent is amino, alkylamino of 1 to 4 carbon atoms, dialkylamino of 1 to 4 carbon atoms in each alkyl group, cycloalkyl of 3 to 10 carbon atoms, hydroxy, COO alkyl of 1 to 4 carbon atoms, phenyl, or pyridyl); alkenyl of 2 to 6 carbon atoms; alkynyl of 3 to 6 carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of 1 to 4 carbon atoms, halo, alkoxy of 1 to 4 carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylamino, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: (1) alkylenimino having 3 to 13 carbon atoms; (2) alkylenimino having 3 to 13 carbon atoms which may contain one double bond and/or is mono- or disubstituted with alkyl having 1 to 4 carbon atoms, hydroxy, phenyl, or benzyl; (3) alkylenimino having 3 to 13 carbon atoms which is either bridged by an alkylene group having 1 to 3 carbon atoms, or is fused to a phenyl ring, or is attached by a spiro linkage to an ethylene ketal group; (4) homopiperazinyl; homopiperazinyl substituted with alkyl having 1 to 4 carbon atoms; piperazinyl; or piperazinyl substituted with alkyl having 1 to 4 carbon atoms, dialkyl having 1 to 4 carbon atoms in each alkyl group, phenyl, COO alkyl having 1 to 4 carbon atoms in the alkyl group, trifluoromethylphenyl, halophenyl, benzyl, or pyridyl; and (5) morpholino; dialkylmorpholino having 1 to 4 carbon atoms in each alkyl group; provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 53
Independent Claim
417 words
A method for treating an animal infected with meningitis by administering to said animal a therapeutically effective amount of a quinoline thiosemicarbazone compound of the formula ##STR27## or a pharmaceutically-acceptable acid addition salt thereof wherein R.sub. is alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 10 carbon atoms; substituted alkyl of 1 to 12 carbon atoms (wherein the substituent is amino, alkylamino of 1 to 4 carbon atoms, dialkylamino of 1 to 4 carbon atoms in each alkyl group, cycloalkyl of 3 to 10 carbon atoms, hydroxy, COO alkyl of 1 to 4 carbon atoms, phenyl, or pyridyl); alkenyl of 2 to 6 carbon atoms; alkynyl of 3 to 6 carbon atoms; substituted benzyl (wherein the substituent is methyl or phenyl on the alpha carbon atom, or the substituent is methyl, dimethyl, halo, dihalo, or ethoxy on the phenyl ring); adamantyl; phenyl; naphthyl; substituted phenyl or substituted naphthyl (wherein the ring is mono-, di-, or trisubstituted and the substituents are alkyl of 1 to 4 carbon atoms, halo, alkoxy of 1 to 4 carbon atoms, hydroxy, phenoxy, trifluoromethyl, dimethylamino, diethylamino, or pyridyl; thienyl; indolyl; furyl; acridyl; quinolyl; or pyridazinyl; and R 2 is hydrogen or is selected from the group of radicals listed above for R 1 , in which case R 1 and R 2 may be the same or different; or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of: (1) alkylenimino having 3 to 13 carbon atoms; (2) alkylenimino having 3 to 13 carbon atoms which may contain one double bond and/or is mono- or disubstituted with alkyl having 1 to 4 carbon atoms, hydroxy, phenyl, or benzyl; (3) alkylenimino having 3 to 13 carbon atoms which is either bridged by an alkylene group having 1 to 3 carbon atoms, or is fused to a phenyl ring, or is attached by a spiro linkage to an ethylene ketal group; (4) homopiperazinyl; homopiperazinyl substituted with alkyl having 1 to 4 carbon atoms; piperazinyl; or piperazinyl substituted with alkyl having 1 to 4 carbon atoms, dialkyl having 1 to 4 carbon atoms in each alkyl group, phenyl, COO alkyl having 1 to 4 carbon atoms in the alkyl group, trifluoromethylphenyl, halophenyl, benzyl, or pyridyl; and (5) morpholino; dialkylmorpholino having 1 to 4 carbon atoms in each alkyl group; provided that: when R 2 is hydrogen, then R 1 cannot be ethyl, isopropyl, or monochlorophenyl.
Claim 54
Dependent Claim
14 words
The method of claim 47 wherein the quinoline thiosemicarbazone compound is 1-Azacycloheptane-1-thiocarboxylic acid 2-[1-(2-quinolyl)-ethylidene]hydrazide.
Claim 55
Dependent Claim
14 words
The method of claim 47 wherein the quinoline thiosemicarbazone compound is 3-Azabicyclo[3.2.2]noname-3-thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 56
Dependent Claim
15 words
The method of claim 47 wherein the quinoline thiosemicarbazone compound is 4-(2-Pyridyl)piperadino thiocarboxzylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 57
Dependent Claim
14 words
The method of claim 47 wherein the quinoline thiosemicarbazone compound is Pyrrolidine-1-thiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 58
Dependent Claim
14 words
The method of claim 47 wherein the quinoline thiosemicarbazone compound is 1-Propyl-aminothiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 59
Dependent Claim
14 words
The method of claim 47 wherein the quinoline thiosemicarbazone compound is Dissobutylaminothiocarboxylic acid 2-[1-(2-quinolyl)ethylidene]hydrazide.
Claim 60
Dependent Claim
28 words
A method for treating an animal which has a bacterial infection by administering to said animal a therapeutically effective amount of a quinoline thiosemicarbazone compound of claim 1.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1987-04-03 | 1987-10-03 | 1988-04-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-04-03 | 1991-10-03 | 1992-04-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-04-03 | 1995-10-03 | 1996-04-03 | $7700.00 | Window Closed / Lapsed |