GB1565734A - Fused triazoles - Google Patents
Fused triazoles Download PDFInfo
- Publication number
- GB1565734A GB1565734A GB1844877A GB1844877A GB1565734A GB 1565734 A GB1565734 A GB 1565734A GB 1844877 A GB1844877 A GB 1844877A GB 1844877 A GB1844877 A GB 1844877A GB 1565734 A GB1565734 A GB 1565734A
- Authority
- GB
- United Kingdom
- Prior art keywords
- radical
- formula
- compound
- gastric
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/12—Oxygen or sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The triazolothiadiazine derivatives correspond to the formula I <IMAGE> in which R1 to R6 and n have the meanings given in Claim 1. These derivatives and their addition salts with pharmaceutically acceptable acids can be used as active substances of therapeutic compositions, especially for treating gastric ulcers.
Description
(54) FUSED TRLAZOLES (71) We, LAROCHE NAVARRON S.A., a French Body Corporate of 20,
Rue Jean Jaurès, 92800 PUTEAUX, France, do hereby declare the invention for which we pray that a patent may be granted to us and the method by which it is to be performed to be particularly described in and by the following statement:- This invention relates to new triazolothiadiazine derivatives, to a process for their preparation and to their applications, particularly for therapeutic purposes.
The present invention relates to compounds having the general formula:
in which:
R1 represents a hydrogen atom, a trifluoromethyl radical, a straight- or branched
chain C10 alkyl radical, a C7 cycloalkyl radical, a C10 alkyl-C37 cycloalkyl
radical, an aryloxy-C,~ealkyl radical, an aryl radical, an aryl-C,~6alkyl radical, a
saturated or unsaturated heterocyclic radical such as thienyl or furyl, a hetero
cyclic alkyl radical, a radical of the formula
in which R, is a hydroxy, cyano or C16 alkoxy radical and R8 is a C18 alkyl or
aryl radical,
R2 and R3 represent independently a hydrogen atom, an aryl radical, a C 18alkyl radical, a C37 cycloalkyl radical, a C16 alkyloxycarbonyl radical, a C1-6alkyl-
carbamoyl radical, a carboxy radical or a cyano radical, n is 0, 1, 2 or 3,
R4 represents a hydrogen atom, a C16alkyl radical, an aryl radical, a hydroxyl
radical, or a C1-6alkyloxy radical,
R5 represents hydrogen, and
R6 represents a hydrogen atom, a C1-6Alkyl radical, a C1-6alkylcarbonyl radical, an
arylcarbonyl radical or an aryl-C16alkylcarbonyl radical, or when n =0, R5 and
R6 represent together a single bond, and their pharmaceutically acceptable acid
addition salts.
In the above definition, the term aryl refers to a phenyl radical substituted with one, two or three radicals independently selected from hydrogen, halogen,
C1-6alkyl, C1-6alkyloxy, C26alkenyloxy, C2-6alkynyloxy, C1-6alkylthio, trifluoromethyl, C1-4alkylenedioxy and the nitro group.
The acid-addition salts may typically be those formed with hydrohalic, sulfuric, nitric, phosphoric, formic, acetic, maleic, fumaric, methanesulfonic, lactic, succinic, tartric acids and acidic metal salts such as disodium orthophosphate and monopotassium sulfate. In addition, the free bases may exist in a hydrated or a substantially anhydrous form.
The compounds of the formula (I) may be prepared by reacting a 4-amino-4H1,2,4-triazole-3-thiol of the formula (II) with an a-halo ketonic derivative of the formula (III) (Method A), or a dihalo derivative of the 1,2,4-triazole-3-thiol of the formula (II) with an a-halo ketonic derivative of the formula (IV) (Method B), according to the following reaction schemes:
Method A
MethodiB
in which R1, R2, R3, R4 and R5 have the above-defined meanings and X is halogen.
This reaction is advantageously effected in an inert anhydrous solvent or without solvent at the refluxing temperature, for about 4 to 24 hours.
The compounds of the formula (II) may be prepared:
I) by cyclization of a potassium dithiocarbazinate in the presence of hydrazine in
the hot in aqueous medium, according to the following reaction scheme:
2) by cyclization of a methyl dithiocarbazinate in the presence of hydrazine within
refluxing ethanol, according to the following reaction scheme:
3) by condensation of a carboxylic acid with 3-thiocarbohydrazide at temperatures
from 90"C to 1500C in the presence or in the absence of a solvent, according to
the following reaction scheme:
The compounds of the formula (I) in which R8 is other than hydrogen may be produced by action of an alkylating or acylating agent on a compound of the formula (Ib), according to conventional methods.
In addition, some compounds of the formula (Ib) may be obtained by reduction of a compound of the formula (Ia), according to conventional methods.
EXAMPLE 1.
3-Benzyl-6-methyl-7H- 1 ,2,4-triazolo[3,4b] 1 ,3,4-thiadiazine hydrochloride
(a) Intermediate 4-amino-5-benzyl-4H- 1 ,2,4-triazole-3-thiol may be prepared as
follows:
Method I
To a cooled stirred solution containing 84 g (1.5 mole) potassium hydroxide and 150 g (1 mole) phenylaceto-hydrazine in 1 litre absolute alcohol are added 114 g (1.5 mole) carbon disulfide. After three hours, the reaction mixture is poured over
I litre ethyl ether. The resulting precipitate is suction filtered, washed with 3 x 100 ml ethyl ether, and is then dried.
Potassium 3-benzyl-dithiocarbazinate (221 g; 0.95 mole) and hydrazine (48 g) in 500 ml water are refluxed during one hour, with stirring. The reaction mixture is then poured over ice and is made acidic with concentrated hydrochloric acid. The resulting white precipitate is washed with water and then recrystallized from aqueous ethyl alcohol, to give 4-amino-5-benzyl-4H-1,2,4-triazole-3-thiol which melts at 1720C.
N.M.R. (DMSO de) 7.4 ppm, 5H,s 13.6 ppm, 1H, s (S--H) 4.15 ppm, 2H, s
5.65 ppm (2H), s (NH2)
Method 2
To a cooled stirred solution containing 8.4 g (0.15 mole) potassium hydroxide and 15 g (0.1 mole) phenylaceto-hydrazide in 100 ml absolute alcohol are added 11.4 g (0.15 mole) carbon disulfide. After 3 hours, water (30 ml) is added, followed by the dropwise addition of methyl iodide (14.2 g). The methyl ester precipitates out after 30 minutes on further addition of 100 ml water.
24 g (0.1 mole) of the previously obtained methyl 3-benzyldithiocarbazinate and 5 ml hydrazine in 100 ml ethyl alcohol are refluxed during 12 hours. The reaction mixture is poured over ice and is then made acidic with concentrated hydrochloric acid. The compound obtained after recrystallization is identical with that obtained with method 1.
Method 3
3-Thiocarbohydrazide (10.6 g) and phenylacetic acid (13.6 g) are heated during 3 hours at 1500C. After cooling, anhydrous ether (200 ml) is added thereto. The resulting precipitate is suction filtered and then recrystallized from aqueous alcohol.
(b) 4-Amino-5-benzyl-4H-1,2,4-triazole-3-thiol (15 g; 0.073 mole) prepared
according to method 1, 2 or 3, and chloroacetone (6.75 g) are refluxed during
12 hours. The resulting material crystallizes on cooling, after which the
resulting crystals are suction filtered. Recrystallization from absolute alcohol
gives a compound which melts at 2520 C.
N.M.R. (DMSO d6) 7.4 ppm, 5H,s 4 ppm,2H,s 11.8 ppm,(H+)s 4.3 ppm, 2H, s
2.35 ppm, 3H, s (CH3)
EXAMPLE 2.
3-Benzyl-6-methyl-5,6-dihydro-7H- 1 ,2,4-triazolo[3,4b] 1 ,3,4-thiadiazine hydrochloride
While maintaining the temperature between 0 C and 5"C, potassium borohydride (6.2 g) is added portionwise to a solution of sodium hydroxide (3 g) and the compound obtained in Example 1(21.8 g) in methanol (150 ml). After the addition, stirring is continued during 20 hours at room temperature, after which the solvent is evaporated off and the residue is dissolved in methylene chloride (100 ml) and washed with water. The hydrochloride is extracted according to the conventional method, to give a compound which melts at 1700 C.
EXAMPLE 3.
3-Benzyl-5,6-dihydro-7H- 1 ,2,4-triazolo[3,4bi 1 ,3,4-thiadiazepine hydrobromide
4-Amino-5-benzyl-4H-l ,2,4-triazole-3-thiol (15 g) and l-bromo-3-chloropropane (8 ml) in absolute alcohol (100 ml) are refluxed during 4 hours. The solvent is then evaporated off and the residue is recrystallized from aqueous alcohol. The resulting compound melts at 230"C.
C: theory: 44.04% H: theory: 4.67% N: theory: 17.12%
found: 43.91% found: 4.59% found: 17.13%
The following compounds were prepared according to the procedure of
Example 1.
EXAMPLE 4.
3 - Phenyl - 6 - ethoxy - 7H - 1,2,4 - triazolo[3,4b]1,3,4 - thiadiazine hydrobromide. M.p. = 146 C.
EXAMPLE 5.
3 - Methyl - 6 - ethoxy - 7H - 1,2,4 - triazolo - [3,4b]1,3,4 - thiadiazine hydrochloride. M.p. = 130"C.
EXAMPLE 6.
3 - ortho - Methoxyphenyl - 6 - methyl - 7H - 1,2,4 - triazolo[3,4b]1,3,4 - thiadiazine hydrochloride. M.p. = 170 C.
EXAMPLE 7.
3 - para - Methoxybenzyl - 6 - methyl - 7H - 1,2,4 - triazolo[3,4b] 1,3,4 - thiadiazine hydrochloride. M.p. = 1370C.
EXAMPLE 8.
3 - para - Chlorophenyl - 6 - methyl - 7H - 1,2,4 - triazolo[3,4b] 1,3,4 - thiadiazine hydrochloride. M.p. = 155 C.
EXAMPLE 9.
3 - para - Chlorobenzyl - 6 - methyl - 7H - 1,2,4 - triazolo[3,4b]1,3,4 - thiadiazine hydrochloride. M.p. = 140 C.
EXAMPLE 10.
3 - Propyl - 6 methyl - 7 - phenyl - 7H - 1,2,4 - triazolo[3,4b] 1,3,4 - thiadiazine hydrochloride. M.p. = 116 C.
EXAMPLE 11.
3 - Benzyl - 6 - phenyl - 7H - 1,2,4 - triazolo[3,4b]1,3,4 - thiadiazine hydrochloride. M.p. = 1550C.
EXAMPLE 12.
3 - Benzyl - 6,7 - diphenyl - 7H - 1,2,4 - triazolo[3,4b]1,3,4 - thiadiazine hydrochloride. M.p. = 165 C.
EXAMPLE 13.
3 - para - Nitrobenzyl - 6 - methyl - 7H - 1,2,4 - triazolo[3,4b] 1,3,4 - thiadiazine hydrochloride. M.p. = 2100C.
EXAMPLE 14.
3 - cr - Methyl - benzyl - 6 - methyl - 711 - 1,2,4 - triazolo[3,4b] 1,3,4 - thiadiazine hydrochloride. M.p. = 106"C.
EXAMPLE 15.
3(3 - Phenyl - Propyl) - 6 - methyl - 711 - 1,2,4 - triazolo[3,4b] 1,3,4 - thiadiazine hydrochloride. M.p. = 1300C.
EXAMPLE 16.
3 - para - Hydroxybenzyl - 6 - methyl - 7H - 1,2,4 - triazolo[3,4b]1,3,4 - thiadiazine hydrochloride. M.p. = 1720C.
EXAMPLE 17.
3. - Benzyl - 6 - ethoxy - 7H,1,2,4 - triazolo[3,4b]1,3,4 - thiadiazine hydrochloride. M.p. = 95 C.
EXAMPLE 18.
3-Cyclopropane - 6 - methyl - 711 - 1,2,4 - triazolo[3,4b]1,3,4 - thiadiazine hydrochloride. M.p. = 1520C.
EXAMPLE 19.
3 - para - Chlorophenoxymethyl - 6 - methyl - 711 - 1,2,4 - triazolo[3,4b] - 1,3,4thiadiazine. M.p. = 136 C.
EXAMPLE 20.
3 - para - Fluorobenzyl - 6 - methyl - 711 - 1,2,4 - triazolo[3,4b] - 1,3,4 - thiadiazine hydrochloride. M.p. = 120 C.
EXAMPLE 21.
3 - Benzyl - 6 - ethyl - 7 - phenyl - 711 - 1,2,4 - triazolo[3,4b] - 1,3,4 - thiadiazine hydrochloride. M.p. = 1560C.
Applicant found that the compounds of the formula (I) and their pharmaceutically acceptable acid addition salts have the property of reducing gastric secretions and are therapeutically valuable materials, particularly for reducing acidic gastric secretions and for the treatment of gastric and duodenal ulcers.
Pharmacological data which provide evidence of this property are given below.
The following procedure was used to investigate the action of the derivatives of the formula (I) on the inhibition of gastric acid secretion. The technique is based on a test for the determination of the ability of a compound to modify the gastric secretion (volume and total acidity) induced in rats by ligation of the pylorus [Method according to Shay, 1945, modified by Kim and Shore (J. Pharmacol. Exp.
Ther., 141, 321, 1963)].
The investigation was carried out with groups of 10 female S.P.F. rats (Sprague
Dawley strain) weighing about 150 g, kept fasting during 48 hours prior to the test and given only a mixed glucose-sodium chloride solution. On the day of the test, the pylorus was ligated under ether anesthesia, and the rats were sacrificed 4 hours later. The gastric secretion was collected and, after centrifugation, the volume and total acidity were determined (titration with N/100 NaOH, Ph meter).
All the test materials were investigated at a dosage of 100 mg/kg, per os. The results obtained are given in the Table below. The activities are expressed as percent inhibition, with respect to the reference animals, on the volume of gastric secretion and on total acid production.
Percent inhibition on the volume of gastric Percent inhibition on Example secretion total acidity 1 53% 37% 2 30% 20% 7 57% 20% 8 65% 31% 14 49% 7% 15 67% 39% 18 52% 38.5% Thus, this invention includes also within its scope therapeutic compositions comprising, as active ingredient, a compound of formula (I) or a pharmaceutically acceptable acid addition salt thereof, typically together with a pharmaceutically acceptable excipient.
Said therapeutic compositions may be administered orally or parenterally.
The compositions may typically be formulated as capsules, tablets or injectable solutions.
They may contain 160 wt% active ingredient, depending on the route of administration.
The daily dosage may be from 0.1 to 3 g of active ingredient by the oral route and from 0.05 to 1.5 g of active ingredient by the parenteral route.
WHAT WE CLAIM IS:
1. A compound having the general formula:
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (6)
1. A compound having the general formula:
in which:
R, represents a hydrogen atom, a trifluoromethyl radical, a straight- or branched
chain C16 alkyl radical a C cycloalkyl radical, a C18 alkyl-C36 cycloalkyl
radical, an aryloxy-C1-6alkyl radical, an aryl radical, an aryl-C1-6alkyl radical, a
saturated or unsaturated heterocyclic radical such as thienyl or furyl, a
heterocyclic alkyl radical, a radical of the formula
in which R7 is a hydroxy, cyano or C16 alkoxy radical and R8 is a C16 alkyl or
aryl radical,
R2 and R3 represent independently a hydrogen atom, an aryl radical, a C1-6alkyl
radical, a C37 cycloalkyl radical, a C16 alkoxycarbonyl radical, a
C1-8alkylcarbamoyl radical, a carboxy radical or a cyano radical, n is 0, 1, 2 or 3,
R4 represents a hydrogen atom, a C16 alkyl radical, an aryl radical, a hydroxyl
radical, or a C,~ealkyloxy radical,
R5 represents hydrogen, and R6 represents a hydrogen atom a a 6alkyl radical, a C1-8alkylcarbonyl radical, an arylcarbonyl radical or an aryl-C1-6alkylcarbonyl radical, or, when n =0, R5
and R6 represent together a single bond, or a pharmaceutically acceptable acid
addition salt thereof.
2. A process for the preparation of a compound of the formula Ia
in which R1, R2, R3 and R4 have the meanings given in claim 1, comprising reacting a compound of the formula
in which R1 has the meaning given in claim 1, with a halogenated derivative of the formula
in which R2, R3 and R4 have the meanings given in claim 1 and X is a halogen atom.
3. A process for the preparation of a compound of the formula Ib
in which R1, R2, R3 and R4 have the meanings given in claim I and R5 is a hydrogen atom, comprising reacting a compound of the formula II:
in which R1 has the meaning given in claim 1, with a dihalogenated derivative of the formula
in which R2, R3 and R4 have the meanings given in claim 1, R5 is a hydrogen atom and X is a halogen atom.
4. A therapeutic composition comprising as active ingredient a compound of formula I as claimed in claim 1 or a pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable excipient.
5. A compound as claimed in claim 1, substantially as described in any one of the Examples.
6. A process as claimed in claim 2 or in claim 3, substantially as described in any one of the Examples.
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1844877A GB1565734A (en) | 1977-05-03 | 1977-05-03 | Fused triazoles |
CH442978A CH632763A5 (en) | 1977-05-03 | 1978-04-25 | Triazolothiadiazine derivatives and processes for preparing them |
DE19782818395 DE2818395A1 (en) | 1977-05-03 | 1978-04-27 | DERIVATIVES OF TRIAZOLTHIADIAZINES, THE PROCESS FOR THEIR MANUFACTURING AND MEDICINAL PRODUCTS CONTAINING THEM |
FR7812767A FR2396012A1 (en) | 1977-05-03 | 1978-04-28 | TRIAZOLOTHIADIAZINE DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR THERAPEUTIC APPLICATIONS |
ES469840A ES469840A1 (en) | 1977-05-03 | 1978-05-02 | Fused triazoles |
BE187338A BE866648A (en) | 1977-05-03 | 1978-05-03 | TRIAZOLOTHIADIAZINE DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR THERAPEUTIC APPLICATIONS |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1844877A GB1565734A (en) | 1977-05-03 | 1977-05-03 | Fused triazoles |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1565734A true GB1565734A (en) | 1980-04-23 |
Family
ID=10112615
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB1844877A Expired GB1565734A (en) | 1977-05-03 | 1977-05-03 | Fused triazoles |
Country Status (6)
Country | Link |
---|---|
BE (1) | BE866648A (en) |
CH (1) | CH632763A5 (en) |
DE (1) | DE2818395A1 (en) |
ES (1) | ES469840A1 (en) |
FR (1) | FR2396012A1 (en) |
GB (1) | GB1565734A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108484600A (en) * | 2017-05-26 | 2018-09-04 | 江苏新元素医药科技有限公司 | The URAT1 inhibitor of uricosuric excretion |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4411905A (en) * | 1979-09-04 | 1983-10-25 | Richardson-Merrell Inc. | Antisecretory 1,2,4-triazole-3-thiols |
JPH02145588A (en) * | 1988-11-29 | 1990-06-05 | Konica Corp | Production of 1,2,4-triazolo(3,4-b)-1,3,4-thiadiazine based compound substituted by heteroatom at 6-position |
WO2000010564A1 (en) * | 1998-08-21 | 2000-03-02 | Competitive Technologies, Inc. | 4-amino-3-mercapto-1,2,4-triazoles |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL227262A (en) * | 1957-04-26 | |||
US3954981A (en) * | 1975-04-28 | 1976-05-04 | Richardson-Merrell Inc. | Triazolocycloalkylhydrothiadiazine derivatives |
-
1977
- 1977-05-03 GB GB1844877A patent/GB1565734A/en not_active Expired
-
1978
- 1978-04-25 CH CH442978A patent/CH632763A5/en not_active IP Right Cessation
- 1978-04-27 DE DE19782818395 patent/DE2818395A1/en not_active Withdrawn
- 1978-04-28 FR FR7812767A patent/FR2396012A1/en active Granted
- 1978-05-02 ES ES469840A patent/ES469840A1/en not_active Expired
- 1978-05-03 BE BE187338A patent/BE866648A/en unknown
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108484600A (en) * | 2017-05-26 | 2018-09-04 | 江苏新元素医药科技有限公司 | The URAT1 inhibitor of uricosuric excretion |
CN108484600B (en) * | 2017-05-26 | 2022-12-13 | 江苏新元素医药科技有限公司 | URAT1 inhibitors for promoting uric acid excretion |
Also Published As
Publication number | Publication date |
---|---|
FR2396012A1 (en) | 1979-01-26 |
ES469840A1 (en) | 1978-12-16 |
CH632763A5 (en) | 1982-10-29 |
DE2818395A1 (en) | 1978-11-16 |
FR2396012B1 (en) | 1982-07-09 |
BE866648A (en) | 1978-11-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NZ207156A (en) | (2 quinazolinyl)-oxalkylamide derivatives and pharmaceutical compositions | |
FR2643903A1 (en) | NOVEL BENZIMIDAZOLE DERIVATIVES, PROCESSES FOR PREPARING SAME, SYNTHESIS INTERMEDIATES, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, IN PARTICULAR FOR THE TREATMENT OF CARDIOVASCULAR DISEASES, AND DUODENIAL ULCERS | |
EP0506194A1 (en) | 4-aryl-thiazole or imidazole derivatives | |
EP0040401A1 (en) | Triazoloquinoxalin-4-ones and such oxaline-4-thiones | |
HU184797B (en) | Process for preparing quinazoline derivatives | |
CS274405B2 (en) | Method of 4-cyanopyridazines preparation | |
EP0721949B1 (en) | Indoline compound and 5-ht 3? receptor antagonist containing the same as active ingredient | |
US4086353A (en) | Certain azolinylamino (azolidinylimino) indazoles | |
SK46793A3 (en) | Regenarative melting tank and method of working | |
AU630397B2 (en) | 4,5,6,7-tetrahydrobenzimidazole derivatives | |
IE862996L (en) | PHENOXY-SUBSTITUTED ß-CARBOLINE DERIVATIVES | |
RU2695383C2 (en) | Bendamustine derivatives, related compounds and their medical application for treating cancer | |
GB1565734A (en) | Fused triazoles | |
DE2800062A1 (en) | BENZO-CONDENSED HETEROCYCLIC FOOT FRINGE, THEIR PRODUCTION AND USE | |
US3732243A (en) | 2-(p-bromophenyl)-9-dimethyl-amino-propyl-9h-imidazo(1,2-a)benzimidazole | |
CA1171083A (en) | Tricyclic pyrroles, a process for their preparation, their use, and medicaments containing them | |
US3953461A (en) | Amino derivatives of thiazolo[5,4-b]pyridine-6-carboxylic acids and esters | |
JP2008501766A (en) | Substituted tricyclic benzimidazoles | |
JPH04330078A (en) | Substituted thieno(2,3-b)(1,4)thiazine-6-sulfonamide as antiglaucoma agent | |
US4221798A (en) | Hypotensive 2-heterocycloamino-imidazolines | |
US5672604A (en) | 1-phenylmethyl benzimidazole piperazine derivative | |
US4292323A (en) | Phenyl-1,2,3,4-tetrahydrocarbazoles and use thereof | |
IE59173B1 (en) | Imidazo[1,2-a]quinoline derivatives, their preparation and their application in therapy | |
US3946010A (en) | 3-Phenyl-2,5-dihydro-as-triazin-6 (1H)-ones | |
EP0216323A2 (en) | Quinolonecarboxylic acid derivatives and their preparation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PS | Patent sealed | ||
PCNP | Patent ceased through non-payment of renewal fee |