CN108358856B - It is a kind of prevent and treat peptic ulcer drug with and its preparation method and application - Google Patents
It is a kind of prevent and treat peptic ulcer drug with and its preparation method and application Download PDFInfo
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- CN108358856B CN108358856B CN201810014266.XA CN201810014266A CN108358856B CN 108358856 B CN108358856 B CN 108358856B CN 201810014266 A CN201810014266 A CN 201810014266A CN 108358856 B CN108358856 B CN 108358856B
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Abstract
The present invention provides a kind of Quinazol derivative and its officinal salt, the Quinazol derivative can inhibit H well+‑K+Atpase activity, and there is significant preventive and therapeutic action for the gastric ulcer of aspirin induction, its effect is even better than conventional medicament Omeprazole, is a kind of proton pump inhibitor, is suitable as the therapeutic agent of gastric ulcer especially peptic gastric ulcer.
Description
Technical field
The present invention relates to pharmaceutical technology fields, and specifically, it to be quinazoline that the present invention provides a kind of proton pump inhibitors
Ketone derivatives and its officinal salt have the effect of good prevention and treatment peptic ulcer.
Background technique
Peptic ulcer refers mainly to betide stomach and duodenal chronic ulcer, is a frequently-occurring disease, common disease.Ulcer
It is formed with various factors, wherein acidic gastric juice is the Fundamentals of ulcer formation to the digestion of mucous membrane, is hence obtained one's name.It is acid
Gastric juice contact any position, as distal esophagus, the postoperative previous anastomotic of gastrointestinal anastomosis, jejunum and with Ectopic Gastric Mucosa
Meckel diverticulum, most of ulcer betide duodenum stomach function regulating, therefore also known as taste-blindness rate.Initial treatment
Method mainly uses antiacid (such as sodium bicarbonate, aluminium hydroxide) neutralization gastric acid to achieve the purpose that mitigate symptom.20th century
After the seventies, with H2The discovery of the acid secretion inhibitors such as receptor blocking pharmacon, proton pump inhibitor has started digestibility and has burst
Ulcer treatment new era, these drugs by be located at parietal cell top film constitute secretory micro-pipe and intracytoplasmic tubular foam
On H+-K+Adenosine triphosphatase causes the inhibition of the enzyme irreversibility, so that effective gastric acid secretion inhibiting, has and take effect
Fastly, the high feature of ulcer healing rate greatly reduces surgical operation rate.
Patent US4255431 discloses the proton pump inhibitor of first listing, i.e. Omeprazole.By its unique treatment
Effect, in anti-ulcer medicament market and H2In the competition of receptor antagonist, windward is gradually obtained, 1996, it is smooth to become the first in the world
Medicine is sold, and occupies first place for successive years.After Omeprazole, new proton pump inhibitor constantly comes out, and successively lists also
Lansoprazole, Pantoprazole, Rabeprazole and esomeprazole.
However, current proton pump inhibitor class drug has the following deficiencies: that the effect of the reaching most strong time is longer, it can be with it
Apparent interaction occurs for its drug, and pharmacokinetics individual difference is big.
Therefore new proton pump inhibitor is developed as market needs.
Summary of the invention
For this purpose, the present invention provides a kind of novel proton pump inhibitor, the effect with good prevention and treatment peptic ulcer
Fruit.
It is an advantage of the invention to provide a kind of Quinazol derivative and its officinal salts.
It is a further object of the invention to provide one kind to contain at least one Quinazol derivative and its can medicine
Use salt as the pharmaceutical composition of main active.
A further object of the invention is, provides the Quinazol derivative and its officinal salt as proton pump
Purposes in terms of inhibitor is more particularly controlled being used to prepare especially for preparing the purposes in terms of proton pump inhibitor
Treat the purposes in terms of the drug of peptic ulcer.
The present invention relates to the Quinazol derivative of logical formula (I) and its officinal salts:
Wherein,
R1、R2、R3、R4It is identical or different, it is independent are as follows: hydrogen, halogen, hydroxyl, nitro, cyano, amino, C1-6 alkane
Base, C1-6 alkoxy, C1-6 alkoxy C 1-6 alkyl, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, C1-6 alkyl amino, two
(C1-6 alkyl) amino, C1-6 alkyl-carbonyl, C1-6 alkoxy carbonyl, C6-10 aryl or C6-10 aryl C1-6 alkyl；
R5Are as follows: hydrogen, C1-6 alkyl, halogenated C1-6 alkyl or hydroxyl C1-6 alkyl；
R6、R7It is identical or different, it is independent are as follows: hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkyl,
Halogenated C1-6 alkoxy, C1-6 alkyl amino, two (C1-6 alkyl) amino, hydroxyl, hydroxyl C1-6 alkyl or amino；
R8Are as follows: hydrogen, C1-6 alkyl, carboxyl, C1-6 alkyl-carbonyl or C1-6 alkoxy carbonyl, wherein the C1-6 alkyl
Optionally replaced by halogen, hydroxyl, carboxyl or amino.
In one embodiment, the R1、R2、R3、R4It is identical or different, it is independent are as follows: hydrogen, hydroxyl, C1-6 alkane
Oxygroup, two (C1-6 alkyl) amino, C1-6 alkoxy carbonyl or C6-10 aryl.
In one embodiment, the R5Are as follows: hydrogen.
In one embodiment, the R6Are as follows: hydrogen or C1-6 alkyl；The R7Are as follows: hydrogen.
In one embodiment, the R8Are as follows: hydrogen, C1-6 alkyl, hydroxyl C1-6 alkyl, halogenated C1-6 alkyl or C1-6
Alkyl-carbonyl.
In one embodiment, the Quinazol derivative and its officinal salt of the logical formula (I) are:
" C1-6 alkyl " of the present invention indicates the alkyl containing 1-6 carbon atom of linear chain or branched chain, such as methyl, second
Base, n-propyl, isopropyl, normal-butyl, isobutyl group, sec-butyl, tert-butyl, n-pentyl, isopentyl, 2- methyl butyl, neopentyl,
1- ethyl propyl, n-hexyl, isohesyl, 4- methyl amyl, 3- methyl amyl, 2- methyl amyl, 1- methyl amyl, 3,3- diformazan
Base butyl, 2,2- dimethylbutyl, 1,1- dimethylbutyl, 1,2- dimethylbutyl, 1,3- dimethylbutyl, 2,3- dimethyl
Butyl, 2- ethyl-butyl, 1- methyl -2- methyl-propyl etc..
" C6-10 aryl " of the present invention refers to 6 to the 10 yuan of full carbon monocycles or fused polycycle of the pi-electron system with conjugation
Group, such as phenyl and naphthalene.
" halogen " of the present invention indicates fluorine, chlorine, bromine, iodine.
The officinal salt of the Quinazol derivative of logical formula (I) all acid-addition salts in particular.It can be specifically mentioned
Be that pharmacology is acceptable commonly used in the inorganic acid of pharmacy or the salt of organic acid.These are suitable to be and acid for example below
Water-soluble and water-insoluble acid-addition salts: hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, maltonic acid, benzene
Formic acid, 2- (4- hydroxy benzoyl) benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, lauric acid, malic acid, succinic acid, grass
Acid, tartaric acid, pamoic acid, stearic acid, toluenesulfonic acid, methanesulfonic acid or 3- hydroxyl -2- naphthoic acid, wherein whether being one according to the acid
First acid or more anacidities and which kind of salt is needed, these acid are used to prepare salt with equimolar ratio or with the ratio being different from.
The unacceptable salt of pharmacology can be obtained initially, such as prepare chemical combination according to the present invention on an industrial scale
The unacceptable salt of this pharmacology is transformed into pharmacology by the process product in object by methods known to those skilled in the art
Learn acceptable salt.
It is known to those skilled in the art that compound according to the present invention and its salt, such as when they are separated with crystal type
When, it may include different amounts of solvent.Therefore the invention also includes all solvations of the Quinazol derivative of logical formula (I)
Object, and all solvates of the salt of especially all hydrates and the Quinazol derivative of logical formula (I), and it is special
It is not all hydrates.
Compound according to the present invention can be synthesized from corresponding initial compounds, such as according to reaction given below
Scheme.The synthesis is to carry out in a manner known in the art, such as be more fully described in the examples below.
Using the compound for leading to formula (II) as raw material, reacted in generation under alkaline condition with dichloro pyrimidine derivative (III)
Intermediate compounds therefor (IV), then react to obtain the Quinazol derivative of logical formula (I) with the compound of logical formula (V):
In above-mentioned steps, R1-R8Definition it is as described herein.
The invention further relates to a kind of pharmaceutical composition, the Quinazol derivative containing at least one logical formula (I)
And its officinal salt is as main active, and optionally includes excipient and/or adjuvant.
Pharmaceutical preparation can be applied in the form of dosage unit, each dosage unit include predetermined amount activity at
Point.This unit may include the chemical combination of the present invention of such as 0.5mg to 1g, preferably 1mg to 700mg, particularly preferred 5mg to 100mg
Object, Specific amounts depends on disease event to be treated, method of administration, patient age, weight and situation or pharmaceutical preparation can be with
It is applied in the form of dosage unit, each dosage unit includes the active constituent of predetermined amount.
Pharmaceutical preparation can be prepared as by way of any desired proper method application, for example, can by oral administration,
Rectum, intranasal, part or the form of parental routes application.This preparation can be according to known technique systems all in pharmaceutical technology
It is standby, such as prepared by mixing active constituent with excipient or adjuvant.
Pharmaceutical preparation suitable for oral administration can be used as the unit application of separation, such as capsule or tablet；
Powder or granule；Solution or suspension in waterborne liquid or non-aqueous liquid；Edible foaming agent or foam-like food
Product；The application of the form of oil-in-water liq emulsion or water-in-oil liquid emulsion.
Thus, for example active constituent can be with oral, non-toxic for the oral application forms of tablet or Capsule form
The mixing such as pharmaceutically acceptable inert excipient such as ethyl alcohol, glycerol, water.By by compound be ground to fine particle size appropriate and by its
It is mixed with the pharmaceutically acceptable excipient ground in the same way for example edible carbohydrate such as starch or mannitol to prepare
Powder.Equally usable corrigent, preservative, dispersing agent and dyestuff.
In addition, if expectation or it is necessary to, can equally be introduced in mixture suitable adhesive, lubricant and disintegrating agent and
Dyestuff.Suitable adhesive includes starch, gelatin, natural carbohydrate such as glucose, the sweetener by corn preparation, natural and conjunction
At rubber such as Arabic gum, carboxymethyl cellulose, polyethylene glycol, wax etc..
Liquid oral such as solution, syrup and elixir can be prepared in the form of dosage unit, contain specified rate
The compound of predetermined amount.Compound can be dissolved in the aqueous solution containing suitable corrigent and prepare syrup, can be used nontoxic
Alcoholic vehicle prepares elixir.It can disperse compound in non-toxic carrier and prepare suspension.Cosolvent and emulsification can equally be added
Agent such as ethoxylated isostearyl alcohols class and polyoxyethylene sorbitol ethers, preservative, Flavouring agents such as peppermint oil, crude sweet
Taste agent or saccharin or other artificial sweeteners etc..
Drug suitable for local application can be prepared as ointment, creme, suspension, lotion, powder, solution, paste
Agent, gelling agent, spray, aerosol or finish.
Pharmaceutical preparation suitable for being locally applied to mouth includes dragee, pastille and collutory.
Pharmaceutical preparation suitable for rectal administration can be applied in the form of suppository or enema.
Pharmaceutical preparation suitable for parenteral administration includes aqueous and non-aqueous sterile injection solution, wherein containing anti-oxidant
Agent, buffer, bacteriostatic agent and solute, the solute can make preparation and blood samples of patients to be treated isotonic；Aqueous and non-aqueous nothing
Bacterium suspension, contains suspension medium and thickener.The preparation can be in single dose or multi-dose container such as sealed ampoule
It applies in bottle and bottle, and is stored with lyophilised state, to only need that sterile carrier liquid is added for example before facing use
Water for injection.
Self-evident, in addition to the above-mentioned component that should be particularly mentioned that, the preparation can also contain the certain kinds in the prior art
The usually used other ingredients of the preparation of type；Thus, for example the preparation for being suitable for being administered orally can contain corrigent.
Beneficial effect
Quinazol derivative of the present invention can inhibit H well+-K+Atpase activity, and for
The gastric ulcer of aspirin induction has significant preventive and therapeutic action, and effect is even better than conventional medicament Omeprazole,
It is a kind of novel proton pump inhibitor, is suitable as the therapeutic agent of gastric ulcer especially peptic gastric ulcer.
Specific embodiment
Invention is described further below with reference to embodiment, but is not limit the scope of the invention.
Embodiment 1:2- (6- (4- (2- ethoxy) piperazine -1- base) -2- methylpyrimidine -4- base amino) -5,7- dimethoxy
Base quinazoline -4 (3H) -one (compound A)
- 4 (3H) -one 2.21g of 2- methyl -4,6- dichloro pyrimidine 1.63g, 2- amino -5,7- dimethoxyquinazoline is added
Enter into 50mL DMF, under ice bath stirring, 60%NaH 0.8g is added portionwise in reaction solution, reacts at room temperature 6h, reacted
2mL glacial acetic acid is added after complete and terminates reaction.Reaction solution is poured into 100mL saturated sodium bicarbonate solution, solid is precipitated, is filtered,
Washing, dry cake, tetrahydrofuran are recrystallized to give 2- (6- chloro-2-methyl pyrimidine-4-yl amino) -5,7- dimethoxy quinoline azoles
Quinoline -4 (3H) -one 2.98g, yield 85.2%.ESI-MS:348.08 [M+H]+。
By 2- (6- chloro-2-methyl pyrimidine-4-yl amino)-(3H) -one 1.74g, 2- (piperazine of 5,7- dimethoxyquinazoline -4
Piperazine -1- base) ethyl alcohol 0.87g, n,N-diisopropylethylamine (DIPEA) 0.97g, 5mL DMSO is added in 60mL dioxane,
110 DEG C of reaction 8h, fully reacting.Reaction solution is poured into 200mL ice water, 0.5h, filtering are stirred.Dry cake, ethyl alcohol are tied again
Crystalline substance obtains 2- (6- (4- (2- ethoxy) piperazine -1- base) -2- methylpyrimidine -4- base amino) -5,7- dimethoxyquinazoline -4
(3H) -one white solid 1.54g, yield 69.7%.
ESI-MS:442.21 [M+H]+
Elemental analysis: theoretical value/measured value, C (57.13/57.22), H (6.16/6.08), N (22.21/22.31), O
(14.50/14.39)
1H NMR(400MHz,DMSO-D6)δ10.23(s,1H),8.87(s,1H),6.68(s,1H),6.54(s,1H),
5.27(s,1H),4.18(s,1H),3.88(s,6H),3.64(t,4H),3.43(t,4H),3.30(t,2H),2.54(t,2H),
2.44(t,3H)。
Embodiment 2:2- (6- (4- Acetylpiperazine -1- base) -2- methylpyrimidine -4- base amino) -4- oxo -3,4- dihydro
Quinazoline -6- carboxylate methyl ester (compound B)
By 2- methyl -4,6- dichloro pyrimidine 1.63g, 2- amino -4- oxo -3,4- dihydroquinazoline -6- carboxylate methyl ester
2.19g is added in 50mL DMF, and under ice bath stirring, 60%NaH 0.8g is added portionwise in reaction solution, reacts at room temperature 7h,
2mL glacial acetic acid is added after fully reacting and terminates reaction.Reaction solution is poured into 100mL saturated sodium bicarbonate solution, solid is precipitated,
Filtering, washing, dry cake, tetrahydrofuran are recrystallized to give 2- (6- chloro-2-methyl pyrimidine-4-yl amino) -4- oxo -3,4-
Dihydroquinazoline -6- carboxylate methyl ester 2.81g, yield 81.2%.ESI-MS:346.06 [M+H]+。
By 2- (6- chloro-2-methyl pyrimidine-4-yl amino) -4- oxo -3,4- dihydroquinazoline -6- carboxylate methyl ester 1.72g,
1- (piperazine -1- base) ethyl ketone 0.84g, DIPEA 0.97g, 5mL DMSO are added in 100mL dioxane, 110 DEG C of reactions
10h, fully reacting.Reaction solution is poured into 300mL ice water, 0.5h, filtering are stirred.Dry cake, recrystallizing methanol obtain 2-
(6- (4- Acetylpiperazine -1- base) -2- methylpyrimidine -4- base amino) -4- oxo -3,4- dihydroquinazoline -6- carboxylate methyl ester
White solid 1.73g, yield 79.5%.
ESI-MS:438.18 [M+H]+
Elemental analysis: theoretical value/measured value, C (57.66/57.72), H (5.30/5.19), N (22.41/22.30), O
(14.63/14.79)
1H NMR(400MHz,DMSO-D6)δ10.24(s,1H),8.92(s,1H),8.32(d,1H),8.01(s,1H),
7.64(d,1H),5.27(s,1H),3.88(s,3H),3.78(t,4H),3.54(t,4H),2.44(s,3H),2.31(s,3H)。
In a similar way, using the following compound of corresponding Material synthesis:
Pharmacological examples Example
Pharmacological experimental example 1: the compounds of this invention is to H+-K+The inhibition of atpase activity
In the 40mM Tri(Hydroxymethyl) Amino Methane Hydrochloride buffer solution that pH is 7.40, by the present inventionization of various concentration
Close the methanol solution and H of object A-E and positive control Omeprazole+-K+Adenosine triphosphatase is (according to changing for Saccomani et al.
It into method (Biochem.and Biophys.Acta, 464,313,1977), is prepared with the substrate body of gland of fresh hog gastric mucosa)
After the protein mixing of 10 μ g/ml, then 15mM potassium chloride is added in the constant temperature incubation 30min at 37 DEG C.After 10min, then plus
Entering 3mM magnesium chloride and atriphos makes adenosine triphosphate enzyme reaction start to carry out.After 10min, according to Yoda's and Hokin
The amount for the inorganic phosphate that method (Biochem.Biophys.Res.Com., 40,880,1970) measurement releases.
The molten of a certain experimental compound is being added by subtracting in the amount that inorganic phosphate released in check experiment is only added
The amount for the inorganic phosphate released after liquid indicates gained difference divided by the amount of the inorganic phosphate of check experiment with percentage again,
Inhibitory effect IC50It indicates.Experimental result is shown in following table 1:
Table 1: the compounds of this invention is to H+-K+The inhibiting effect of atpase activity
| Compound | IC50(μM) |
| Omeprazole | 11.2 |
| Compound A | 0.53 |
| Compound B | 0.78 |
| Compound C | 0.42 |
| Compound D | 1.01 |
| Compound E | 0.92 |
Test result shows the compounds of this invention to H+-K+The activity of adenosine triphosphatase has good inhibitory effect,
It has been even more than positive control Omeprazole.
Pharmacological experimental example 2: inhibiting effect of the compounds of this invention to gastric ulcer caused by aspirin
Six week old cleaning grade Wistar rats are taken, male, 140~180g, 70, every group 10, respectively model group, sun
Property control group, compound A-E group；Aomei is administered according to the dosage of 10mg/Kg in positive controls, compound A-E group rat respectively
Draw azoles and compound A-E.After each group Rat Fast can't help water 24 hours, positive controls, compound A-E group press 0.2ml/ respectively
The corresponding drug of 10g weight stomach-filling is scattered in the solution of distilled water, and model group presses the weight stomach-filling distilled water of 0.2ml/10g.Greatly
After 30min is administered in mouse, put to death mouse after each group equal stomach-filling aspirin 150mg/kg, 4h, open mouse peritoneal, ligation cardia and
Pylorus and injected through stomach wall into gastral cavity 1% formalin 2ml, by stomach take out immerse 1% formalin in, it is big along stomach after 30min
Curved to split, stomach ulcer is observed under disecting microscope, and a situation arises, calculates ulcer area and ulcer inhibition rate.Concrete outcome is such as
Shown in table 2.Statistical method experimental result indicates that data are handled using t inspection with mean ± standard deviation:
Table 2: influence of the compounds of this invention to gastric ulcer caused by aspirin
Note: compared with model group, P < 0.01 *；Compared with positive controls,#P<0.05
Test result shows that large area gastric ulcer occur in model group rats, illustrates that the gastric ulcer of aspirin induction is built
Mould success.Compared with model group rats, the gastric ulcer area of each compound group of the present invention is substantially reduced (P < 0.01), shows this hair
Bright compound has good preventive and therapeutic action for gastric ulcer.Even compared with positive control Omeprazole, the present invention
The pharmacological effect of compound is more prominent (P < 0.05).
In conclusion Quinazol derivative of the present invention can inhibit H well+-K+Adenosine triphosphate enzyme activity
Property, and there is significant preventive and therapeutic action for the gastric ulcer of aspirin induction, effect is even better than traditional medicine
Object Omeprazole, therefore it is suitable as the therapeutic agent of peptic gastric ulcer.
The foregoing describe the preferred embodiment for the present invention, and however, it is not to limit the invention.Those skilled in the art couple
Embodiment disclosed herein can carry out the improvements and changes without departing from scope and spirit.
Claims (10)
1. a kind of Quinazol derivative and its officinal salt of logical formula (I):
Wherein,
R1、R2、R3、R4It is identical or different, it is independent are as follows: hydrogen, hydroxyl, amino, C1-6 alkoxy, C1-6 alkyl amino, two
(C1-6 alkyl) amino, C1-6 alkoxy carbonyl or C6-10 aryl；
R5Are as follows: hydrogen or C1-6 alkyl；
R6、R7It is identical or different, it is independent are as follows: hydrogen or C1-6 alkyl；
R8Are as follows: hydrogen, C1-6 alkyl or C1-6 alkyl-carbonyl, wherein the C1-6 alkyl is optionally replaced by halogen or hydroxyl.
2. the Quinazol derivative and its officinal salt of logical formula (I) according to claim 1, which is characterized in that the R1
For hydrogen or C1-6 alkoxy；R2For hydrogen, hydroxyl, C1-6 alkoxy carbonyl or C6-10 aryl；R3For hydrogen or two (C1-6 alkyl) ammonia
Base；R4For hydrogen.
3. the Quinazol derivative and its officinal salt of logical formula (I) according to claim 1, which is characterized in that the R5
Are as follows: hydrogen.
4. the Quinazol derivative and its officinal salt of logical formula (I) according to claim 1, which is characterized in that the R6
Are as follows: hydrogen or C1-6 alkyl；The R7Are as follows: hydrogen.
5. the Quinazol derivative and its officinal salt of logical formula (I) according to claim 1, which is characterized in that the R8
Are as follows: hydrogen, C1-6 alkyl, hydroxyl C1-6 alkyl, halogenated C1-6 alkyl or C1-6 alkyl-carbonyl.
6. the Quinazol derivative and its officinal salt of logical formula (I) according to claim 1, which is characterized in that described
The Quinazol derivative of logical formula (I) is selected from:
7. a kind of method for the Quinazol derivative for preparing logical formula (I) according to claim 1, the method packet
It includes:
Using the compound for leading to formula (II) as raw material, is reacted under alkaline condition with dichloro pyrimidine derivative (III) and generate intermediate
Compound (IV), then react to obtain the Quinazol derivative of logical formula (I) with the compound of logical formula (V):
In above-mentioned steps, R1-R8Definition as described in the appended claim 1.
8. a kind of pharmaceutical composition, the quinazoline containing at least one logical formula (I) according to claim 1-6
Ketone derivatives and its officinal salt are as main active, and optionally include excipient and/or adjuvant.
9. the Quinazol derivative and its officinal salt of logical formula (I) according to claim 1-6 are in preparation matter
Purposes in sub- pump inhibitor.
10. the Quinazol derivative and its officinal salt of logical formula (I) according to claim 1-6 are controlled in preparation
Treat the purposes in the drug of peptic ulcer.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1123028A (en) * | 1993-05-12 | 1996-05-22 | 纳幕尔杜邦公司 | Fungicidal fused bicyclic pyrimidinones |
| CN1845924A (en) * | 2003-07-02 | 2006-10-11 | 弗·哈夫曼-拉罗切有限公司 | Arylamine-substituted quinazolinone compounds |
| CN102260245A (en) * | 2011-06-02 | 2011-11-30 | 南开大学 | 2,3-dihydro-quinazolinone derivative, and preparation method and application thereof |
-
2018
- 2018-01-08 CN CN201810014266.XA patent/CN108358856B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1123028A (en) * | 1993-05-12 | 1996-05-22 | 纳幕尔杜邦公司 | Fungicidal fused bicyclic pyrimidinones |
| CN1845924A (en) * | 2003-07-02 | 2006-10-11 | 弗·哈夫曼-拉罗切有限公司 | Arylamine-substituted quinazolinone compounds |
| CN102260245A (en) * | 2011-06-02 | 2011-11-30 | 南开大学 | 2,3-dihydro-quinazolinone derivative, and preparation method and application thereof |
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