CA1085840A - 6,7-dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine and related sulfoxide and sulfone - Google Patents
6,7-dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine and related sulfoxide and sulfoneInfo
- Publication number
- CA1085840A CA1085840A CA294,994A CA294994A CA1085840A CA 1085840 A CA1085840 A CA 1085840A CA 294994 A CA294994 A CA 294994A CA 1085840 A CA1085840 A CA 1085840A
- Authority
- CA
- Canada
- Prior art keywords
- dimethoxy
- quinazolinamine
- thiomorpholinyl
- dioxide
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
Novel quinazoline derivatives of the formula:
Novel quinazoline derivatives of the formula:
Description
34~
This invention relates to quinazoline derivatives having the following formula:
CH30 ~ N l N 5~(0~n wherein n is O, l or 2.
The compounds of the present invention are prepared -~
by reacting the chloroquinazoline V with thiomorepholine or thiomorpholine S,S-dioxide in accordance with the following scheme:
~H2 " ~:
CH30 ~ N ~
l l I + HN S_(0) ~ :
CH30 \ N ~ Cl ~
CH30 ~ N
CH30 ~ N ~ N 5=(0) n IA n - O
IB n = 2 On the other hand when the quinazoline derivative of the present invention is desired where n is l, the compound where n is O is oxidized with one equivalent of a suitable oxidizing agent such as m-chloroperbenzoic acid in accordance with the following scheme:
C~130 ~ N ~ [ ]CH30 ~ ~N
CH30 N l N S > CH30 N l N ~ -0 IA IC
r3~ q Sii8~(~
In another aspect of the invention, there is provided a pharmaceutical composition comprising a compound of formula I
as has been defined or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier.
The pharmaceutically acceptable salts of the free compounds of general formula I may be prepared by conventional reactions with equivalent amounts of inorganic or organic acid solutions. As exemplary of pharmaceutically acceptable salts there are the salts of hydrochloric, hydrobromic, sulfuric, benzenesulphonic, acetic, oxalic, malic, and citric acids.
The compounds of general formula I, as well as their pharmaceutically acceptable inorganic and organic acid salts, may be administered enterally or parenterally in admixture with a liquid or solid pharmaceutical diluent or carrier. As in-jection medium it is preferred to use water which contains the conventional pharmaceutical adjuvants for injection solutions such as stabilizing agents, solubilizing agents and buffers, for example, ethano1, complex-forming agents such as ethylene diamine tetraacetic acid, tartrate, and citrate buffers and highly molecular weight polymers such as polyethylene oxide for viscosity regulation. Examples of carrier materials include starch, lactose, mannitol, methylcellulose, talc, highly dis-persed silicic acids, high molecular weight fatty acids such as stearic acid, and high molecular weight polymers such as poly-ethylene glycols. Oral forms of administration may, of course, contain flavoring, sweetening, preserving, suspending, thicken-ing, or emulsifying agents.
A particular aspect of the formula composition comprises a compound of formula I in an effective unit dose form. By "effective unit dose" is meant a predetermined amount sufficient to be effective to bring about the desired hypo-tensive reaction.
~35~
In yet a further aspect of the invention, there is provided a method of producing a hypotensive action in mammals, including man, which comprises the administration of an effective depressant amount of a compound of general formula I
or a pharmaceutically acceptable salt thereof.
The dosage of the compounds of formula I or their pharmaceutically acceptable salts depends, of course, on the nature and severity of the excitability to be countered, as well as the path of administration. When tested in spontane-ously hypertensive rats to determine hypotensive activity, thecompound of example I for example, was active at a dose of 10 mg/kg and the compound of example 3 was active at a dose of 30 mg/kg. The compounds and their pharmaceutically acceptable salts are active as hypotensives in mammals when administered orally9 parenterally, or intravenously throughout a dose range of 1.0 - 100.0 mg/kg of mammalian body weight 9 preferably in the range of 5.0 - 50.0 mg/kg. In addition, these compounds appear to have less undesirable ~-blocking activity than Prazosin generic term for the 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)piperazine.
It is believed that one of ordinary skill in the art, can, using the preceding description, utilize the present invention to its fullest extent. The following specific embodiments, are, therefore, to be simply construed as merely illustrative and not to limit the remainder of the specifi-cation and claims in any way whatsoever.
C H 3 0 ~N ll~ S
B~C9 6,7-Dimethoxy-2-(4-khiomorpholinyl)-4-quinazolinamine A mixture of 8.00 g of 2-chloro-6,7-dimethoxy-4-quinazolinamine and 6.90 g of thiomorpholine in 80 ml of chlorobenzene was refluxed for 18 hrs. The reaction mixture was cooled to room temperature, and the precipitate was col-lected. There was deposited 8.00 g (70.2~) of white powder, mp 267-269, dec. The product was recrystallized from methanol to give an analytical sample, mp 270-271, dec.
Anal. Calcd. for C14H18N402S-HCl: C, 49.05; H, 5.59;
Cl, 10.34; N, 16.34; S, 9.35. Found: C, 48.91i H, 5.59;
Cl, 10.53; N, 16.18; S, 9.51.
CH30 ~ N
CH30 N l N 5-0 /
6,7-Dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine S-oxide To a solution of 1.00 g of 6,7-dimethoxy-2-(4-thio-morpholinyl)-4-quinazolinamine in 100 ml of methylene chloride at 0 was added drop~ise over 15 min. a solution of 0.66 g of 85% _-chloroperbenzoic acid in 25 ml of methylene chloride.
After an additional 2 hrs. at 0, the reaction mixture was washed with dilute sodium bicarbonate and water. The organic extracts were dried over anhydrous sodium sulfate, and the solvent was evaporated. There remained 0.75 g (71.4%) of white powder, mp 278-280, dec. Recrystallization from methylene chloride-isopropanol gave an analytical sample, mp 283-285, . dec.
Anal. Calcd. for C14H18N4035: C, 52.16; H, 5-63;
N, 17.38; S, 9.95. Found: C, 51.92; H, 5.82; N, 17.04;
S, 9.82.
8~(~
` NH2 CH30 ~ N
C~130J~\Nl~l S2 , /
6,7-Dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine S,S-dioxide A mixture of 9.40 g of 2-chloro-6,7-dimethoxy-4-quinazolinamine and 10.6 g of thiomorpholine S,S-dioxide in 200 ml of chlorobenzene was refluxed for 24 hrs. The reaction mixture was cooled to room temperature, and the precipitate was collected. There was deposited 9.10 g (61.1%) of white powder, mp 271-275, dec. Recrystallization from aqueous ethanol gave a pure product, mp 275-276 dec.
Anal. Calcd. for C14H18N44S-HCl C, 44.86j H, 5.11i Cl, 9.46; N, 14.95; S, 8.55. Found: C, 44.93, H, 5.13;
Cl, 9.19; N9 14.83; S, 8.49.
As stated earlier, the compounds of this invention are suitably and generally administered in oral dosage form, such as by tablet or capsule, by combining the same in an effective amount with any oral pharmaceutically acceptable `
inert diluent, such as lactose, starch, dicalcium phosphate, calcium sulfate, kaolin, mannitol and powdered sugar. In addition, when required, suitable binders, lubricants, disinte-grating agents, and coloring agents can also be added. Typical binders include starch, gelatin, sugars such as sucrose, molasses, and lactose, natural and synthetic gums such as acacia sodium alginate, extract of Irish moss, carboxymethyl cellulose, methylcellulose, and polyvinylpyrrolidone, poly~
ethylene glycol, ethylcellulose, and waxes. Typical lubricants for use in these dosage forms can include, without limitation, ~5~
boric acid, sodium benzoate, sodium acetate, sodium chloride, leucine, and polyethylene glycol. Suitable disintegrators can include, without limitation, starch, methyl cellulose, agar, bentonite, cellulose and wood products, alginic acid, guar gum~
; citris pulp, carboxymethyl cellulose, and sodium lauryl sulfate. If desired, conventionally pharmaceutically accepta-ble dyes such as any of the standard FD ~ C dyes may be incorporated into the dosage unit form.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention and without departing from the spirit and scope thereof can make various changes and/or modifications to the invention for adapting it to various usages and conditions.
Accordingly, such changes and modifications are probably intended to be within the full range of equivalents of the following claims. ~-
This invention relates to quinazoline derivatives having the following formula:
CH30 ~ N l N 5~(0~n wherein n is O, l or 2.
The compounds of the present invention are prepared -~
by reacting the chloroquinazoline V with thiomorepholine or thiomorpholine S,S-dioxide in accordance with the following scheme:
~H2 " ~:
CH30 ~ N ~
l l I + HN S_(0) ~ :
CH30 \ N ~ Cl ~
CH30 ~ N
CH30 ~ N ~ N 5=(0) n IA n - O
IB n = 2 On the other hand when the quinazoline derivative of the present invention is desired where n is l, the compound where n is O is oxidized with one equivalent of a suitable oxidizing agent such as m-chloroperbenzoic acid in accordance with the following scheme:
C~130 ~ N ~ [ ]CH30 ~ ~N
CH30 N l N S > CH30 N l N ~ -0 IA IC
r3~ q Sii8~(~
In another aspect of the invention, there is provided a pharmaceutical composition comprising a compound of formula I
as has been defined or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier.
The pharmaceutically acceptable salts of the free compounds of general formula I may be prepared by conventional reactions with equivalent amounts of inorganic or organic acid solutions. As exemplary of pharmaceutically acceptable salts there are the salts of hydrochloric, hydrobromic, sulfuric, benzenesulphonic, acetic, oxalic, malic, and citric acids.
The compounds of general formula I, as well as their pharmaceutically acceptable inorganic and organic acid salts, may be administered enterally or parenterally in admixture with a liquid or solid pharmaceutical diluent or carrier. As in-jection medium it is preferred to use water which contains the conventional pharmaceutical adjuvants for injection solutions such as stabilizing agents, solubilizing agents and buffers, for example, ethano1, complex-forming agents such as ethylene diamine tetraacetic acid, tartrate, and citrate buffers and highly molecular weight polymers such as polyethylene oxide for viscosity regulation. Examples of carrier materials include starch, lactose, mannitol, methylcellulose, talc, highly dis-persed silicic acids, high molecular weight fatty acids such as stearic acid, and high molecular weight polymers such as poly-ethylene glycols. Oral forms of administration may, of course, contain flavoring, sweetening, preserving, suspending, thicken-ing, or emulsifying agents.
A particular aspect of the formula composition comprises a compound of formula I in an effective unit dose form. By "effective unit dose" is meant a predetermined amount sufficient to be effective to bring about the desired hypo-tensive reaction.
~35~
In yet a further aspect of the invention, there is provided a method of producing a hypotensive action in mammals, including man, which comprises the administration of an effective depressant amount of a compound of general formula I
or a pharmaceutically acceptable salt thereof.
The dosage of the compounds of formula I or their pharmaceutically acceptable salts depends, of course, on the nature and severity of the excitability to be countered, as well as the path of administration. When tested in spontane-ously hypertensive rats to determine hypotensive activity, thecompound of example I for example, was active at a dose of 10 mg/kg and the compound of example 3 was active at a dose of 30 mg/kg. The compounds and their pharmaceutically acceptable salts are active as hypotensives in mammals when administered orally9 parenterally, or intravenously throughout a dose range of 1.0 - 100.0 mg/kg of mammalian body weight 9 preferably in the range of 5.0 - 50.0 mg/kg. In addition, these compounds appear to have less undesirable ~-blocking activity than Prazosin generic term for the 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)piperazine.
It is believed that one of ordinary skill in the art, can, using the preceding description, utilize the present invention to its fullest extent. The following specific embodiments, are, therefore, to be simply construed as merely illustrative and not to limit the remainder of the specifi-cation and claims in any way whatsoever.
C H 3 0 ~N ll~ S
B~C9 6,7-Dimethoxy-2-(4-khiomorpholinyl)-4-quinazolinamine A mixture of 8.00 g of 2-chloro-6,7-dimethoxy-4-quinazolinamine and 6.90 g of thiomorpholine in 80 ml of chlorobenzene was refluxed for 18 hrs. The reaction mixture was cooled to room temperature, and the precipitate was col-lected. There was deposited 8.00 g (70.2~) of white powder, mp 267-269, dec. The product was recrystallized from methanol to give an analytical sample, mp 270-271, dec.
Anal. Calcd. for C14H18N402S-HCl: C, 49.05; H, 5.59;
Cl, 10.34; N, 16.34; S, 9.35. Found: C, 48.91i H, 5.59;
Cl, 10.53; N, 16.18; S, 9.51.
CH30 ~ N
CH30 N l N 5-0 /
6,7-Dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine S-oxide To a solution of 1.00 g of 6,7-dimethoxy-2-(4-thio-morpholinyl)-4-quinazolinamine in 100 ml of methylene chloride at 0 was added drop~ise over 15 min. a solution of 0.66 g of 85% _-chloroperbenzoic acid in 25 ml of methylene chloride.
After an additional 2 hrs. at 0, the reaction mixture was washed with dilute sodium bicarbonate and water. The organic extracts were dried over anhydrous sodium sulfate, and the solvent was evaporated. There remained 0.75 g (71.4%) of white powder, mp 278-280, dec. Recrystallization from methylene chloride-isopropanol gave an analytical sample, mp 283-285, . dec.
Anal. Calcd. for C14H18N4035: C, 52.16; H, 5-63;
N, 17.38; S, 9.95. Found: C, 51.92; H, 5.82; N, 17.04;
S, 9.82.
8~(~
` NH2 CH30 ~ N
C~130J~\Nl~l S2 , /
6,7-Dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine S,S-dioxide A mixture of 9.40 g of 2-chloro-6,7-dimethoxy-4-quinazolinamine and 10.6 g of thiomorpholine S,S-dioxide in 200 ml of chlorobenzene was refluxed for 24 hrs. The reaction mixture was cooled to room temperature, and the precipitate was collected. There was deposited 9.10 g (61.1%) of white powder, mp 271-275, dec. Recrystallization from aqueous ethanol gave a pure product, mp 275-276 dec.
Anal. Calcd. for C14H18N44S-HCl C, 44.86j H, 5.11i Cl, 9.46; N, 14.95; S, 8.55. Found: C, 44.93, H, 5.13;
Cl, 9.19; N9 14.83; S, 8.49.
As stated earlier, the compounds of this invention are suitably and generally administered in oral dosage form, such as by tablet or capsule, by combining the same in an effective amount with any oral pharmaceutically acceptable `
inert diluent, such as lactose, starch, dicalcium phosphate, calcium sulfate, kaolin, mannitol and powdered sugar. In addition, when required, suitable binders, lubricants, disinte-grating agents, and coloring agents can also be added. Typical binders include starch, gelatin, sugars such as sucrose, molasses, and lactose, natural and synthetic gums such as acacia sodium alginate, extract of Irish moss, carboxymethyl cellulose, methylcellulose, and polyvinylpyrrolidone, poly~
ethylene glycol, ethylcellulose, and waxes. Typical lubricants for use in these dosage forms can include, without limitation, ~5~
boric acid, sodium benzoate, sodium acetate, sodium chloride, leucine, and polyethylene glycol. Suitable disintegrators can include, without limitation, starch, methyl cellulose, agar, bentonite, cellulose and wood products, alginic acid, guar gum~
; citris pulp, carboxymethyl cellulose, and sodium lauryl sulfate. If desired, conventionally pharmaceutically accepta-ble dyes such as any of the standard FD ~ C dyes may be incorporated into the dosage unit form.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention and without departing from the spirit and scope thereof can make various changes and/or modifications to the invention for adapting it to various usages and conditions.
Accordingly, such changes and modifications are probably intended to be within the full range of equivalents of the following claims. ~-
Claims (8)
1. Process for preparing a compound of the general formula:
wherein n is 0, 1 or 2, and pharmaceutically acceptable salts thereof, which comprises A) when n is to be 0 or 2: reacting a chloroquinazoline of the formula:
with thiomorepholine or thiomorpholine S,S-dioxide of the formula:
wherein n is 0 or 2; or B) when n is to be 1: oxidizing the compound obtained in step A where n is 0.
wherein n is 0, 1 or 2, and pharmaceutically acceptable salts thereof, which comprises A) when n is to be 0 or 2: reacting a chloroquinazoline of the formula:
with thiomorepholine or thiomorpholine S,S-dioxide of the formula:
wherein n is 0 or 2; or B) when n is to be 1: oxidizing the compound obtained in step A where n is 0.
2. The process of Claim 1, wherein 2-chloro-6,7-dimethoxy-4-quinazolinamine is reacted with thiomorpholine to form the 6,7-dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine.
3. The process of Claim 2, wherein the compound obtained is oxidized to form the 6,7-dimethoxy-2-(4-thio-morpholinyl)-4-quinazolinamine S-oxide.
4. The process of Claim 1, wherein 2-chloro-6,7-dimethoxy-4-quinazolinamine is reacted with thiomorpholine S,S-dioxide to form the 6,7-dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine S,S-dioxide.
5. Compounds of the general formula:
wherein n is 0, 1 or 2 and pharmaceutically acceptable salts thereof, when prepared by the process defined in Claim 1 or by an obvious chemical equivalent.
wherein n is 0, 1 or 2 and pharmaceutically acceptable salts thereof, when prepared by the process defined in Claim 1 or by an obvious chemical equivalent.
6. The compound according to Claim 1 which is 6,7-dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine, when prepared by the process defined in Claim 2 or by an obvious chemical equivalent.
7. The compound according to Claim 1 which is 6,7-dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine S-oxide, when prepared by the process defined in Claim 3 or by an obvious chemical equivalent.
8. The compound according to Claim 1 which is 6,7-dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine S,S-dioxide, when prepared by the process defined in Claim 4 or by an obvious chemical equivalent.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75969577A | 1977-01-17 | 1977-01-17 | |
| US759,695 | 1977-01-17 | ||
| US05/844,755 US4115565A (en) | 1977-01-17 | 1977-10-25 | 6,7-Dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine and related sulfoxide and sulfone |
| US844,755 | 1977-10-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1085840A true CA1085840A (en) | 1980-09-16 |
Family
ID=27116723
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA294,994A Expired CA1085840A (en) | 1977-01-17 | 1978-01-16 | 6,7-dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine and related sulfoxide and sulfone |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS53108990A (en) |
| AU (1) | AU3233678A (en) |
| CA (1) | CA1085840A (en) |
| DE (1) | DE2800508C3 (en) |
| DK (1) | DK19578A (en) |
| FR (1) | FR2377399A1 (en) |
| GB (1) | GB1544392A (en) |
| IE (1) | IE46285B1 (en) |
| LU (1) | LU78871A1 (en) |
| NL (1) | NL7800550A (en) |
| SE (1) | SE7800458L (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102004027871B3 (en) * | 2004-06-08 | 2006-03-16 | Lanxess Deutschland Gmbh | Process for the preparation of 10α- [4 '- (S, S-dioxothiomorpholin-1'-yl)] - 10-desoxo-10-dihydroartemisinin |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1390015A (en) * | 1971-05-07 | 1975-04-09 | Koninklijke Pharma Fab Nv | 4-amino-quinazoline compounds |
-
1977
- 1977-12-22 IE IE2618/77A patent/IE46285B1/en unknown
-
1978
- 1978-01-05 DE DE2800508A patent/DE2800508C3/en not_active Expired
- 1978-01-10 FR FR7800494A patent/FR2377399A1/en not_active Withdrawn
- 1978-01-10 GB GB869/78A patent/GB1544392A/en not_active Expired
- 1978-01-11 AU AU32336/78A patent/AU3233678A/en active Pending
- 1978-01-13 LU LU78871A patent/LU78871A1/en unknown
- 1978-01-13 JP JP262478A patent/JPS53108990A/en active Pending
- 1978-01-16 SE SE7800458A patent/SE7800458L/en unknown
- 1978-01-16 CA CA294,994A patent/CA1085840A/en not_active Expired
- 1978-01-16 DK DK19578A patent/DK19578A/en unknown
- 1978-01-17 NL NL7800550A patent/NL7800550A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| DE2800508B2 (en) | 1980-02-21 |
| IE46285B1 (en) | 1983-04-20 |
| DK19578A (en) | 1978-07-18 |
| SE7800458L (en) | 1978-07-18 |
| IE46285L (en) | 1978-07-17 |
| AU3233678A (en) | 1979-07-19 |
| FR2377399A1 (en) | 1978-08-11 |
| LU78871A1 (en) | 1978-06-26 |
| GB1544392A (en) | 1979-04-19 |
| DE2800508C3 (en) | 1980-10-16 |
| JPS53108990A (en) | 1978-09-22 |
| NL7800550A (en) | 1978-07-19 |
| DE2800508A1 (en) | 1978-07-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |