US5344928A
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US
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Phenothiazine derivatives, their production and use
Assignee: Takeda Pharmaceutical Co Ltd
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Filing: 1992-04-14
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Granted: 1994-09-06
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Expires: 2012-04-14
Abstract
Abstract There is disclosed a novel phenothiazine derivative of the general formula (I): ##STR1## wherein R 1 , R 2 , R 3 and R 4 are the same or different and are a C 1-6 alkyl group and at least one of them has as a substituent a group which can react with amino group, thiol group or carboxyl group, and X - is a counter ion of the phenazathionium. Their production and the intermediates used in the production are also disclosed. The compound (I) is a derivative of methylene blue and is applicable to photodynamic therapy of cancer or immunoassays utilizing chemiluminescence.
Inventors
- 👤 Hirotomo Masuya
- 👤 Hiroshi Shimadzu
- 👤 Toshio Miyawaki
- 👤 Marvin A. Motsenbocker
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 16:41
CPC Classifications
C; C07; C07D; C07D207/00; C07D207/02; C07D207/30; C07D207/34; C07D207/36; C07D207/40; C07D207/404; C07C; C07C381/00; C07C381/02; C07D279/00; C07D279/10; C07D279/14; C07D279/18; C07D417/00; C07D417/02; C07D417/12; C07D417/14; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/531; G01N33/532; G01N33/533; Y; Y10; Y10S; Y10S436/00; Y10S436/811
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
64 words
A phenothiazine derivative of the formula (I): ##STR16## wherein R 1 , R 2 , R 3 and R 4 are the same or different and are respectively a C 1-6 alkyl group, at least one of which has as a substituent a group which can react with amino group, thiol group or carboxyl group, and X' is a counter ion of the phenazathionium.
Claim 2
Dependent Claim
64 words
A phenothiazine derivative of the formula (I): ##STR16## wherein R 1 , R 2 , R 3 and R 4 are the same or different and are respectively a C 1-6 alkyl group, at least one of which has as a substituent a group which can react with amino group, thiol group or carboxyl group, and X' is a counter ion of the phenazathionium.
Claim 3
Dependent Claim
48 words
A phenothiazine derivative according to claim 1, wherein the substituent is carboxyl group, halogenocarbonyl group, azidocarbonyl group, cyanocarbonyl group, an alkoxycarbonyloxycarbonyl group, a substituted phenoxycarbonyl group, 1-imidazolyl-carbonyl group, 1-benzotriazolyloxycarbonyl group, 5-norbornene-2,3-dicarboximidoxycarbonyl group, succinimidoxycarbonyl group, maleimidoxycarbonyl group, aspartic acid residue, glutamic acid residue, maleimido group, or an aminoalkylcarbamoyl group.
Claim 4
Dependent Claim
56 words
A phenothiazine derivative according to claim 2, wherein the substituent is carboxyl group, chlorocarbonyl group, azidocarbonyl group, cyanocarbonyl group, ethoxycarbonyloxycarbonyl group, isobutoxycarbonyloxycarbonyl group, p-nitrophenoxycarbonyl group, 2,4-dinitrophenoxycarbonyl group, pentachlorophenoxycarbonyl group, 2,4,5-trichlorophenoxycarbonyl group, pentafluorophenoxycarbonyl group, 1-imidazolyl-carbonyl group, 1-benzotriazolyloxycarbonyl group, 5-norbornene-2,3-dicarboximideoxycarbonyl group, succinimidoxycarbonyl group, maleimidoxycarbonyl group, aspattic acid residue, glutamic acid residue, maleimido group, aminoethylcarbamoyl group, or aminodecylcarbamoyl group.
Claim 5
Dependent Claim
32 words
A phenothiazine derivative according to claim 1, wherein the group X is the counter ion formed by a halogen atom, hydroxyl, perchloric acid, sulfuric acid, nitric acid, trifluoroacetic acid or hydrofluoroboric acid.
Claim 6
Dependent Claim
10 words
A phenothiazine derivative according to claim 1, which is hydrophilic.
Claim 7
Dependent Claim
17 words
A phenothiazine derivative according to claim 1 which is 3-[N-methyl-N-(4-succinimidoxycarbonylbutyl)amino]-7-dimethylaminophenazathionium chloride, 3-[N-methyl-N-(5-succinimidoxycarbonylpentyl)amino]-7-dimethylaminophenazathionium chloride, 3-[N-methyl-N-(3-succinimidoxycarbonylpropyl)amino]-7-dimethylaminophenazathionium chloride, 3-[N-methyl-N-(3-succinimidoxycarbonylpropyl)amino]-7-[N-(3-ethoxycarbonylpropyl)-N-methylamino]phenazathionium chloride,
Claim 8
Dependent Claim
21 words
7-bis[N-methyl-N-(3-succinimidoxycarbonylpropyl)amino]phenazathionium chloride, 3-[N-methyl-N-(3-succinimidoxycarbonylpropyl)amino]-7-[N-(3-carboxypropyl)-N-methylamino]phenazathionium chloride, 3-[N-methyl-N-(3-succinimidoxycarbonylpropyl)amino]-7-[N-[3-(1,3-dicarboxypropylcarbamoyl)propyl]-N-methylamino]phenazathionium chloride, 3,7-bis[N-methyl-N-(5-succinimidoxycarbonylpentyl)amino]phenazathionium chloride, 3-[N-methyl-N-(5-succinimidoxycarbonylpentyl)amino]-7-[N-(5-carboxypentyl)-N-methylamino]-phenazathionium chloride, 3-[N-methyl-N-(5-succinimidoxycarbonylpentyl)amino]-7-[N-[5-(1,3-dicarboxypropylcarbamoyl)pentyl]-N-methyamino]phenazathiomium chloride, 3-[N-(3-maleimidopropyl)-N-methylamino]-7-[N-(3-carboxypropyl]-N-methylamino]phenazathionium chloride, 3-[N-(3-maleimidopropyl)-N-methylamino]-7-[N-[3-(1,3-dicarboxypropylcarbamoyl)propyl]-N-methylamino]phenazathionium chloride, 3-[N-(4-maleimidobutyl)-N-methylamino]-7-[N-(4-carboxybutyl)-N-methylamino]phenazathionium chloride, or 3-[N-(4-maleimidobutyl)-N-methylamino]-7-dimethylaminophenazathionium chloride.
Claim 9
Dependent Claim
21 words
7-bis[N-methyl-N-(3-succinimidoxycarbonylpropyl)amino]phenazathionium chloride, 3-[N-methyl-N-(3-succinimidoxycarbonylpropyl)amino]-7-[N-(3-carboxypropyl)-N-methylamino]phenazathionium chloride, 3-[N-methyl-N-(3-succinimidoxycarbonylpropyl)amino]-7-[N-[3-(1,3-dicarboxypropylcarbamoyl)propyl]-N-methylamino]phenazathionium chloride, 3,7-bis[N-methyl-N-(5-succinimidoxycarbonylpentyl)amino]phenazathionium chloride, 3-[N-methyl-N-(5-succinimidoxycarbonylpentyl)amino]-7-[N-(5-carboxypentyl)-N-methylamino]-phenazathionium chloride, 3-[N-methyl-N-(5-succinimidoxycarbonylpentyl)amino]-7-[N-[5-(1,3-dicarboxypropylcarbamoyl)pentyl]-N-methyamino]phenazathiomium chloride, 3-[N-(3-maleimidopropyl)-N-methylamino]-7-[N-(3-carboxypropyl]-N-methylamino]phenazathionium chloride, 3-[N-(3-maleimidopropyl)-N-methylamino]-7-[N-[3-(1,3-dicarboxypropylcarbamoyl)propyl]-N-methylamino]phenazathionium chloride, 3-[N-(4-maleimidobutyl)-N-methylamino]-7-[N-(4-carboxybutyl)-N-methylamino]phenazathionium chloride, or 3-[N-(4-maleimidobutyl)-N-methylamino]-7-dimethylaminophenazathionium chloride.
Claim 10
Dependent Claim
79 words
A phenothiazine derivative of the formula (II): ##STR17## wherein at least one of R 1 ', R 2 ', R 3 ' and R 4 ' is a group of the formula: --(CH 2 )m--CO--Y, the others are C 1-6 alkyl group, Y is a lower alkoxy group having 1 to 4 carbon atoms, an aralkyloxy group or a 1-phenoxy-ethoxy group, m is an integer of 1 to 6 and X - is a counter ion of the phenazathionium.
Claim 11
Dependent Claim
79 words
A phenothiazine derivative of the formula (II): ##STR17## wherein at least one of R 1 ', R 2 ', R 3 ' and R 4 ' is a group of the formula: --(CH 2 )m--CO--Y, the others are C 1-6 alkyl group, Y is a lower alkoxy group having 1 to 4 carbon atoms, an aralkyloxy group or a 1-phenoxy-ethoxy group, m is an integer of 1 to 6 and X - is a counter ion of the phenazathionium.
Claim 12
Dependent Claim
25 words
A phenothiazine derivative according to claim 7, wherein the group Y is methoxy, ethoxy, propoxy, secbutoxy, tert-butoxy, benzyloxy, p-nitrogenzyloxy, p-methylthiobnzyloxy, diphenylmethyloxy, 4-pyridylmethoxy, or 1-phenoxy-ethoxy group.
Claim 13
Dependent Claim
32 words
A phenothiazine derivative according to claim 7, wherein the group X is the counter ion formed by a halogen atom, hydroxyl, perchloric acid, sulfuric acid, nitric acid, trifluoroacetic acid or hydrofluoroboric acid.
Claim 14
Dependent Claim
22 words
A phenothiazine derivative according to claim 7 which is 3-[N-(4-ethoxycarbonylbutyl)-N-methylamino]-7-dimethylaminophenazathionium chloride, 3-[N-(5-ethoxycarbonylpentyl)-N-methylamino]-7-dimethylaminophenazathionium chloride, 3-[N-(3-tert-butoxycarbonylpropyl)-N-methylamino]-7-dimethylaminophenazathionium chloride, 3-[N-(3-tert-butoxycarbonylpropyl)-N-methylamino]-7-[N-(3-ethoxycarbonylpropyl)-N-methylamino]phenazathionium chloride, 3,7-bis]N-(3-tert-butoxycarbonylpropyl)-N-methylamino]phenazathionium chloride, or 3,7-bis]N-(5-ethoxycarbonylpentyl)-N-methylamino]phenazathionium chloride.
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