CN108299418A - A kind of synthetic method of the thiazolyl nicotinamide compound of antiallergy and asthma - Google Patents
A kind of synthetic method of the thiazolyl nicotinamide compound of antiallergy and asthma Download PDFInfo
- Publication number
- CN108299418A CN108299418A CN201810421668.1A CN201810421668A CN108299418A CN 108299418 A CN108299418 A CN 108299418A CN 201810421668 A CN201810421668 A CN 201810421668A CN 108299418 A CN108299418 A CN 108299418A
- Authority
- CN
- China
- Prior art keywords
- thiazolyl
- methyl
- asthma
- antiallergy
- synthetic method
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses the thiazolyl nicotinamide compound formulas of a kind of antiallergy and asthma（Ⅰ）Synthetic method,Wherein, R1Selected from H, F or Cl, R2Selected from H or Cl, R3Selected from H or Cl.Thiazolyl nicotinamide compound formula of the present invention（Ⅰ）For the histamine receptor antagonists of completely new framework types, belong to first public, toxic side effect is low, can be used for the further investigation and exploitation of antihistamine drug, antianaphylaxis disease medicament, asthmatic medicament, has good application prospect in preparing treatment allergy and asthmatic medicament.
Description
The application is the applying date to be September in 2017 14, application No. is 2017108289174, a kind of entitled " thiophene
The divisional application of the patent of oxazolyl nicotinamide compound and its application in preparing antiallergy and asthmatic medicament ".
Technical field
The present invention relates to a kind of synthetic methods of the thiazolyl nicotinamide compound of antiallergy and asthma.
Background technology
H1Expression of receptor is in many cell types, including endothelial cell, most of smooth muscle cells, cardiac muscle, maincenter god
Through system（CNS）Neuron and lymphocyte.H1Receptors signal transduction causes smooth muscle contraction（Including bronchoconstriction）, blood vessel
The vasopermeability of diastole and enhancing, allergy and the anaphylactoid feature of other i.e. hair property.In central nervous system, H1Receptor
Activation is related with egersis.Its activate also in skin and mucosal tissue itch and nociception it is related.For many years, H1Receptor is short of money
The antiallergy and anti-inflammatory activity of anti-agent have been used for treating the lesion that acute and chronic allergic condition and other histamine mediate, and such as send out
Itch and nettle rash.
Ratify the common H used at present1Receptor antagonist pharmaceuticals include：Systemic agents, such as diphenhydramine, cetirizine
（Zyrtec）, Fei Suofennading（Allegra）, Loratadine（Claritin）And Desloratadine（Clarinex）, Yi Jiju
Portion's medicament, such as olopatadine（Patanol、Pataday、Patanase）, Ketotifen, azelastine（Optivar, Astelin）
And epinastine（Elestat）.Traditional purposes included：Anaphylactia and reaction（Such as asthma, rhinitis and other chronic resistances
Plug property tuberculosis）, eye disease（Such as allergic conjunctivitis）, allergic dermatitis and different pathogeny itch.
Invention content
The present invention relates to a kind of thiazolyl nicotinamide compound formulas（Ⅰ）And its in preparing antiallergy and asthmatic medicament
Using.
Wherein, R1Selected from H, F or Cl, R2Selected from H or Cl, R3Selected from H or Cl.
Further, formula（Ⅰ）The compound of expression, its salt or its solvated compounds.
Further, formula（Ⅰ）Synthetic route be
。
Further, the Formula（Ⅰ）Application in preparing antihistamine drug.
Further, the Formula（Ⅰ）Application in preparing antianaphylaxis disease medicament.
Further, the Formula（Ⅰ）Application in preparing anti-asthmatic medicament.
Further, the anaphylactia is itch, nettle rash, allergic rhinitis, allergic dermatitis or anaphylaxis
Conjunctivitis.
Further, a kind of composition, including Formula described in claim 1（Ⅰ）And it is medically acceptable auxiliary
Material.
Advantageous effect：
1. thiazolyl nicotinamide compound formula of the present invention（Ⅰ）For the histamine receptor antagonists of completely new framework types,
Belong to first public, is a kind of stronger histamine receptor antagonists of activity, can be used for antihistamine drug, antianaphylaxis disease medicine
Object depth enters research and development.
2. experiments have shown that thiazolyl nicotinamide compound formula of the present invention（Ⅰ）Contestable with body H1Receptor
In conjunction with and blocking histamine and H1The effect of receptor is played the role of antianaphylactic to inhibit histamine to play biological effect.Anti- group
The experiment of amine screening active ingredients shows such compound compared with positive control astemizole and Desloratadine, has stronger
Anti-histamine activity, MTS methods detect influence of the compounds of this invention to RAW264.7 cell-proliferation activities and show that toxic side effect is low.
3. experiments have shown that thiazolyl nicotinamide compound formula of the present invention（Ⅰ）In the cavy of the asthma caused by histamine
Antiasthmatic effect is better than Desloratadine group.
4. preparation method provided by the invention has reaction condition mild, abundant raw material is easy to get, and operates and post-processes and is simple
The features such as.
Specific implementation mode
The conjunction of 1 N- of embodiment [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5]-niacinamide
At
1, the synthesis of N- [(4- methyl piperazines base -1) methene] -2- (pyridyl group -3) thiazolyl -5- imines
By 2- (pyridyl group -3) thiazolyl -5- amine（10 mmol）With 4- methyl piperazine base -1- formaldehyde（11 mmol）It is dissolved in 40 millis
It rises in methanol, stirs 2 hours, system is not further processed, and directly carries out next step reduction reaction.1H-NMR (400 MHz,
CDCl3) δ: 2.18(s, 3H), 2.25(t, 3H), 3.59(t, 4H), 7.47(t, 1H), 7.59(s, 1H),
8.09(s, 1H), 8.33(d, 1H), 8.70(d, 1H), 9.24(s,1H).
2, the synthesis of N- [(4- methyl piperazines base -1) methyl] -2- (pyridyl group -3) thiazolyl -5- secondary amine
5 milliliters of glacial acetic acids will be added in the reaction solution of previous step, be cooled to 0-5 DEG C, 1.2 grams of sodium borohydrides, low temperature is then added
Lower stirring 2 hours is warmed to room temperature and continues to stir half an hour, 100 milliliters of water are then added into system, stirs 1 hour, filtering,
Obtain 2.1 g yellow solids, as N- [(4- methyl piperazines base -1) methyl] -2- (pyridyl group -3) thiazolyl -5- secondary amine, two steps
Yield totally 73%.1H-NMR (400 MHz, CDCl3) δ: 2.14(s, 3H), 2.32(s, 8H), 4.31(s, 1H),
4.83(s, 1H), 6.82(s, 1H), 7.47(t, 1H), 8.53(d, 1H), 8.70(d, 1H), 9.24(s, 1H),
10.66(s, 1H).
3, the synthesis of N- [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5]-niacinamide
N- [(4- methyl piperazines base -1) methyl] -2- (pyridyl group -3) thiazolyl -5- secondary amine (10 mmol) is dissolved in 40 ml bis-
Chloromethanes solution, is added 10 ml triethylamines thereto, and control temperature is less than 10 DEG C, nicotinoyl chlorine (12 is added dropwise into system
Mmol dichloromethane solution) restores room temperature, stirring at normal temperature 10 hours, then with the sodium carbonate of 50 ml 5% after being added dropwise
Aqueous solution washing reaction system, organic phase anhydrous Na2SO4It is dry, after solvent evaporated, obtained solid flash column chromatography separation,
The light yellow N- of 3.4 g [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5]-niacinamide solid is obtained,
Yield 86%.1H-NMR (400 MHz, CDCl3) δ: 2.14(s, 3H), 2.32(s, 8H), 4.70(s, 2H),
7.45-7.47(m, 2H), 7.75(s, 1H), 8.11(d, 1H), 8.33(d, 1H), 8.70-8.76(m, 2H),
9.00(s, 1H), 9.24(s, 1H).13C-NMR (75 MHz, CDCl3) δ: 46.06, 52.97, 54.39,
72.24, 123.72, 125.61, 132, 133.78, 133.9, 134.25, 135.73, 149.36, 150.34,
151.49, 152.28, 153.97, 164.72, 172.59.LC-MS(ESI, pos, ion) m/z: 395[M+1].
The conjunction of 2 N- of embodiment [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5] -2- fluorine niacinamide
At
N- [(4- methyl piperazines base -1) methyl] -2- (pyridyl group -3) thiazolyl -5- secondary amine (10 mmol) is dissolved in 40 ml bis-
Chloromethanes solution, is added 10 ml triethylamines thereto, and control temperature is less than 10 DEG C, 2- fluorine nicotinoyl chlorine (12 is added dropwise into system
Mmol dichloromethane solution) restores room temperature, stirring at normal temperature 10 hours, then with the sodium carbonate of 50 ml 5% after being added dropwise
Aqueous solution washing reaction system, organic phase anhydrous Na2SO4It is dry, after solvent evaporated, obtained solid flash column chromatography separation,
It is solid to obtain 3.6 g light browns N- [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5] -2- fluorine niacinamide
Body, yield 87%.1H-NMR (400 MHz, CDCl3) δ: 2.14(s, 3H), 2.32(s, 8H), 4.70(s, 2H),
7.47(t, 1H), 7.71(t, 1H), 7.78(s, 1H), 8.33(d, 1H), 8.60-8.70(m, 3H), 9.26(s,
1H). 13C-NMR (75 MHz, CDCl3) δ: 46.06, 52.97, 54.39, 72.24, 116.58, 119.38,
125.61, 133.78, 133.9, 134.25, 138.75, 150.34, 151.27, 152.28, 153.97, 159.2,
164.72, 165.35.LC-MS(ESI, pos, ion) m/z: 413[M+1].
The conjunction of 3 N- of embodiment [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5] -2- chloro-nicotinamides
At
N- [(4- methyl piperazines base -1) methyl] -2- (pyridyl group -3) thiazolyl -5- secondary amine (10 mmol) is dissolved in 40 ml bis-
Chloromethanes solution, is added 10 ml triethylamines thereto, and control temperature is less than 10 DEG C, 2- chloronicotinoyl chlorides (12 are added dropwise into system
Mmol dichloromethane solution) restores room temperature, stirring at normal temperature 10 hours, then with the sodium carbonate of 50 ml 5% after being added dropwise
Aqueous solution washing reaction system, organic phase anhydrous Na2SO4It is dry, after solvent evaporated, obtained solid flash column chromatography separation,
It is solid to obtain 3.8 g yellow N- [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5] -2- chloro-nicotinamides
Body, yield 89%.1H-NMR (400 MHz, CDCl3) δ: 2.14(s, 3H), 2.32(s, 8H), 4.68(s, 2H),
7.44(t, 1H), 7.76(s, 1H), 7.85(t, 1H), 8.30(d, 1H), 8.46(d, 1H), 8.60(d, 1H),
8.67(d, 1H), 9.21(s, 1H).13C-NMR (75 MHz, CDCl3) δ: 46.06, 52.97, 54.39,
72.24, 122.55, 125.61, 133.29, 133.78, 133.9, 134.25, 137.48, 150.34, 150.34,
150.84, 152.28, 153.97, 164.72, 168.71.LC-MS(ESI, pos, ion) m/z: 429[M+1].
The conjunction of 4 N- of embodiment [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5] -4- chloro-nicotinamides
At
N- [(4- methyl piperazines base -1) methyl] -2- (pyridyl group -3) thiazolyl -5- secondary amine (10 mmol) is dissolved in 40 ml bis-
Chloromethanes solution, is added 10 ml triethylamines thereto, and control temperature is less than 10 DEG C, 4- chloronicotinoyl chlorides (12 are added dropwise into system
Mmol dichloromethane solution) restores room temperature, stirring at normal temperature 10 hours, then with the sodium carbonate of 50 ml 5% after being added dropwise
Aqueous solution washing reaction system, organic phase anhydrous Na2SO4It is dry, after solvent evaporated, obtained solid flash column chromatography separation,
It is solid to obtain the light yellow N- of 3.7 g [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5] -4- chloro-nicotinamides
Body, yield 86%.1H-NMR (400 MHz, CDCl3) δ: 2.14(s, 3H), 2.32(s, 8H), 4.70(s, 2H),
7.47(t, 1H), 7.61(d, 1H), 7.79(s, 1H), 8.33(dt, 1H), 8.68-8.70(m, 2H), 9.02
(s, 1H), 9.23(d, 1H).13C-NMR (75 MHz, CDCl3) δ: 46.06, 52.97, 54.39, 72.24,
125.23, 125.61, 131.62, 133.78, 133.9, 134.25, 143.33, 149.56, 150.34,
152.28, 152.67, 153.97, 164.72, 170.94.LC-MS(ESI, pos, ion) m/z: 429[M+1].
The conjunction of 5 N- of embodiment [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5] -6- chloro-nicotinamides
At
N- [(4- methyl piperazines base -1) methyl] -2- (pyridyl group -3) thiazolyl -5- secondary amine (10 mmol) is dissolved in 40 ml bis-
Chloromethanes solution, is added 10 ml triethylamines thereto, and control temperature is less than 10 DEG C, 6- chloronicotinoyl chlorides (12 are added dropwise into system
Mmol dichloromethane solution) restores room temperature, stirring at normal temperature 10 hours, then with the sodium carbonate of 50 ml 5% after being added dropwise
Aqueous solution washing reaction system, organic phase anhydrous Na2SO4It is dry, after solvent evaporated, obtained solid flash column chromatography separation,
Obtain 3.75 g off-white colors N- [(4- methyl piperazines base -1) methyl]-N- [2- (pyridyl group -3) thiazolyl -5] -6- chloro-nicotinamides
Solid, yield 87%.1H-NMR (400 MHz, CDCl3) δ: 2.13(s, 3H), 2.31(s, 8H), 4.69(s, 2H),
7.45-7.53(m, 2H), 7.73(s, 1H), 8.30(dt, 1H), 8.46(dd, 1H), 8.67(m, 1H), 8.98
(d, 1H), 9.27(d, 1H).13C-NMR (75 MHz, CDCl3) δ: 46.06, 52.97, 54.39, 72.24,
124.09, 125.61, 131.65, 133.78, 133.9, 134.25, 136.71, 149.44, 150.34,
152.28, 153.14, 153.97, 164.72, 172.59.LC-MS(ESI, pos, ion) m/z: 429[M+1].
Test example 1：H1Receptor antagonism is tested
The active generally use guinea pig ileum shrinkage of compound antagonism H1 receptors tests to judge.By comparing guinea pig ileum
Contracted length calculates the IC of inhibitory activity value50Value.
Cavy one is taken, its head is hit with mallet and puts to death, split abdominal cavity immediately, find ileocecus, at from ileocecus 1cm
Ileum is cut, one section of about 10cm or so ileum is taken out, is placed in the tyrode's solution culture dish for filling and being filled with air, intestines are removed along intestinal wall
Then ileum is cut into several segments by mesentery（Per 1~1.5cm of segment）, draw tyrode's solution with 5mL syringes and rinse intestinal contents
Totally, it changes spare with fresh tyrode's solution.Pay attention to not pulling intestinal segment when operation in order to avoid influencing contractile function.It takes intestinal tube to be placed in and fills platform
In the culture dish of family name's liquid, at its both ends diagonal wall, threaded respectively with suture needle, and knot.Pay attention to keeping intestinal tube unobstructed, does not make it
Closing.Intestinal tube one end line is lain on ventilation hook hook, is then placed in 37 DEG C of Magnus' baths.Air pump gas outlet is adjusted with screw clamp
Sebific duct, draft speed is escaped one by one with the bubble in Magnus' bath to be advisable.The other end of intestinal tube is added on pulling force transducing again
Device, and Muscle tensility is adjusted to appropriateness, preload 1g.After Ileum From A White stablizes 1h, after recording one section of normal contraction curve, successively
Agents are added dropwise in Magnus' bath.After 0.3 μ g/mL histamine 0.1mL is added, contact 2 minutes, and observe shrinkage amplitude, so
It uses tyrode's solution continuous flushing for several times afterwards, waits for the level before baseline restorer to medication, then record one section of baseline.Plus 10- then
The histamine solution of 5mol/L, each 0.1mL is continuously plus until intestinal contraction reaches maximum value.（Due to histamine action have it is certain
Hysteresis quality will be added when so adding every time at the preceding second largest value once shunk.）Then it elutes for several times, waits for baseline restorer
Originally sample to be tested is added in height, is incubated 15min, then the histamine solution of 10-5mol/L is added as previously described.It should be noted that addition group
The amount that the total amount of amine should be added with last time is consistent.1 compound of table inhibits guinea pig ileum to shrink active IC50。
1 compound of table inhibits guinea pig ileum to shrink active IC50
The compounds of this invention inhibits guinea pig ileum to shrink active IC50Between astemizole and Desloratadine, inhibit to live
Property is strong.Illustrate that compound has the activity of stronger antagonism H1 receptors.
Test example 2：To the antiasthmatic effect of asthmatic guinea pigs caused by histamine
Cavy is taken, is placed in organic glass bell jar, ultrasonic atomizatio sprays into salt histamine solution (0.8mg/mL) 40s, record cavy production
The time of raw asthma, using the time twitched, fallen as incubation period, the cavy for being more than 180s refuses selection, by the cavy selected with
Machine is grouped, every group 10, Normal group, Desloratadine group (1mg/kg), untested compound group (0.1mg/kg).With 2mL/
Kg bw gastric infusions, 60min after administration are respectively put into glass bell jar, similarity condition spraying histamine hydrochloride when by pre-selection
Solution, the incubation period that record asthma occurs in terms of 6min, as a result carry out at statistics if not occurring asthma person yet more than 6min
Reason.The results are shown in Table 2 for it：
Table 2 be test compound antiasthmatic effect result (, n=10)
| Compound number | Incubation period before administration（s） | Incubation period after administration（s） |
| Normal group | 108.2±38.4 | 117.9±42.3 |
| Desloratadine group | 116.7±35.9 | 261.4±43.1* |
| KZAL1007 | 99.7±39.9 | 299.1±37.2* # |
| KZAL1009 | 102.8±32.9 | 311.0±36.4* # |
| KZAL1010 | 102.5±36.4 | 322.9±34.1* # |
| KZAL1018 | 111.0±34.9 | 329.7±34.9* # |
| KZAL1023 | 109.1±36.6 | 312.8±49.9* # |
* compared with Normal group：P<0.05, # compared with Desloratadine group：P<0.05
60min after the compounds of this invention administration, gives histamine hydrochloride solution, it is found that the incubation period that asthma occurs is latent compared with before being administered
Phase, equal conspicuousness extended, and in the case that the compounds of this invention dosage is Desloratadine group 1/10, incubation period is big after administration
In Desloratadine group, illustrate that the compounds of this invention antiasthmatic effect is better than Desloratadine.
Test example 3：The active influence of cell proliferation
Influence of the MTS methods detection compound to RAW264.7 cell-proliferation activities.By cell inoculation in 96 orifice plates, blank is set respectively
Control group, compound group (10 μ g/ mL and 100 μ g/mL various concentrations), every group sets three multiple holes.Add 20 μ L of MTS solution per hole,
It is incubated 1-2 hours, its light absorption value is surveyed under the conditions of wavelength 490nm using microplate reader.It was found that compound group（Two concentration）With it is right
According to group absorbance without significant difference, illustrate that the compounds of this invention does not interfere with the proliferation activity of RAW264.7 cells.
Above-mentioned pharmacological testing shows that the compound of the present invention all has excellent antagonizing histamine function of receptors, has excellent
Antiasthmatic activity, with more plus depth research and development potentiality.
Claims (6)
1. the thiazolyl nicotinamide compound formula of a kind of antiallergy and asthma（Ⅰ）Synthetic method, the formula（Ⅰ）Compound is such as
Under：
Wherein, R1Selected from H, F or Cl, R2Selected from H or Cl, R3Selected from H or Cl, synthetic route is
。
2. the thiazolyl nicotinamide compound formula of antiallergy as described in claim 1 and asthma（Ⅰ）Synthetic method, it is special
Sign is：The synthesis step of described N- [(4- methyl piperazines base -1) methene] -2- (pyridyl group -3) thiazolyl -5- imines is as follows：
2- (pyridyl group -3) thiazolyl -5- amine and 4- methyl piperazine base -1- formaldehyde are dissolved in methanol, stirred, then carries out restoring anti-
It should be to obtain the final product.
3. the thiazolyl nicotinamide compound formula of antiallergy as described in claim 1 and asthma（Ⅰ）Synthetic method, it is special
Sign is：The amount ratio of 2- (pyridyl group -3) thiazolyl -5- amine and 4- methyl piperazine base -1- formaldehyde is 10:11.
4. the thiazolyl nicotinamide compound formula of antiallergy as described in claim 1 and asthma（Ⅰ）Synthetic method, it is special
Sign is：Stirring 2 hours.
5. the thiazolyl nicotinamide compound formula of antiallergy as described in claim 1 and asthma（Ⅰ）Synthetic method, it is special
Sign is：The synthesis step of described N- [(4- methyl piperazines base -1) methyl] -2- (pyridyl group -3) thiazolyl -5- secondary amine is as follows：It will
It prepares in the reaction solution that N- [(4- methyl piperazines base -1) methene] -2- (pyridyl group -3) thiazolyl -5- imines obtains and ice is added
Acetic acid is cooled to 0-5 DEG C, and sodium borohydride is then added, and low temperature 2 hours is warmed to room temperature and continues to stir half an hour, then
Into system be added 100 milliliters of water, stir 1 hour, filtering to get.
6. the thiazolyl nicotinamide compound formula of antiallergy as described in claim 1 and asthma（Ⅰ）Synthetic method, it is special
Sign is：It is describedSynthesis step it is as follows：By N- [(4- methyl piperazines base -1) methyl] -2- (pyridyl groups -
3) thiazolyl -5- secondary amine is dissolved in dichloromethane solution, and triethylamine is added thereto, and control temperature is less than 10 DEG C, is dripped into system
The dichloromethane solution of nicotinoyl chlorine, 2- fluorine nicotinoyl chlorine, 2- fluorine nicotinoyl chlorine, 4- chloronicotinoyl chlorides or 6- chloronicotinoyl chlorides is added, drips
Restore room temperature, stirring at normal temperature 10 hours, then with the aqueous sodium carbonate washing reaction system of 50 ml 5%, organic phase use after finishing
Anhydrous Na2SO4Dry, after solvent evaporated, obtained solid flash column chromatography detaches to obtain the final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810421668.1A CN108299418A (en) | 2017-09-14 | 2017-09-14 | A kind of synthetic method of the thiazolyl nicotinamide compound of antiallergy and asthma |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810421668.1A CN108299418A (en) | 2017-09-14 | 2017-09-14 | A kind of synthetic method of the thiazolyl nicotinamide compound of antiallergy and asthma |
| CN201710828917.4A CN107501258B8 (en) | 2017-09-14 | 2017-09-14 | A kind of thiazolyl nicotinamide compound and its application in preparing antiallergy and asthmatic medicament |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710828917.4A Division CN107501258B8 (en) | 2017-09-14 | 2017-09-14 | A kind of thiazolyl nicotinamide compound and its application in preparing antiallergy and asthmatic medicament |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108299418A true CN108299418A (en) | 2018-07-20 |
Family
ID=60696748
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810421668.1A Withdrawn CN108299418A (en) | 2017-09-14 | 2017-09-14 | A kind of synthetic method of the thiazolyl nicotinamide compound of antiallergy and asthma |
| CN201710828917.4A Expired - Fee Related CN107501258B8 (en) | 2017-09-14 | 2017-09-14 | A kind of thiazolyl nicotinamide compound and its application in preparing antiallergy and asthmatic medicament |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710828917.4A Expired - Fee Related CN107501258B8 (en) | 2017-09-14 | 2017-09-14 | A kind of thiazolyl nicotinamide compound and its application in preparing antiallergy and asthmatic medicament |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN108299418A (en) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ20031902A3 (en) * | 2001-01-31 | 2004-07-14 | Pfizer Products Inc. | Ether derivatives useful as PDE4 isozyme inhibitors |
| CN1914205A (en) * | 2003-12-19 | 2007-02-14 | 葛兰素集团有限公司 | Pyrazolo[3,4-b] pyridine compounds, and their use as phosphodiesterase inhibitors |
| EP1983980A4 (en) * | 2006-01-25 | 2010-05-05 | Synta Pharmaceuticals Corp | Thiazole and thiadiazole compounds for inflammation and immune-related uses |
| US8598174B2 (en) * | 2008-11-12 | 2013-12-03 | Genetech, Inc. | Pyridazinones, method of making, and method of use thereof |
| AU2011293201B2 (en) * | 2010-08-27 | 2015-11-05 | Calcimedica Inc. | Compounds that modulate intracellular calcium |
| JP2014532656A (en) * | 2011-10-28 | 2014-12-08 | シンタ ファーマシューティカルズ コーポレーション | Compounds for inflammation and immune related applications |
-
2017
- 2017-09-14 CN CN201810421668.1A patent/CN108299418A/en not_active Withdrawn
- 2017-09-14 CN CN201710828917.4A patent/CN107501258B8/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN107501258B8 (en) | 2018-10-16 |
| CN107501258A (en) | 2017-12-22 |
| CN107501258B (en) | 2018-08-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2006215080B2 (en) | Pyridyl non-aromatic nitrogenated heterocyclic-1-carboxylate ester derivative | |
| CN103347510B (en) | Lpa receptor antagonist and the purposes in treatment fibrosis thereof | |
| CN1993327B (en) | 3-Carbamoyl-2-pyridone derivative | |
| CN106103422A (en) | Isoquinilone derivatives and application thereof | |
| CN107108679A (en) | E selects the Heterobifunctional inhibitor of albumen and CXCR4 chemokine receptors | |
| CN105254557A (en) | Aryl substituted carboxamide derivatives as calcium or sodium channel blockers | |
| EP1935892A1 (en) | Glycyrrhetinic acid-30-amide derivatives and the uses thereof | |
| EP2351749A1 (en) | Carbamate compound or salt thereof | |
| EA007387B1 (en) | Spirocyclic piperidines as mch1 antagonists and uses thereof | |
| JP2006523641A (en) | Substituted 3-cyanothiophenacetamides as glucagon receptor antagonists | |
| CN106414438A (en) | 2-acylaminothiazole derivative or salt thereof | |
| CN107793408A (en) | Piperidines aminoderivative and its schizoid application for the treatment of | |
| WO2006013054A1 (en) | Substituted n-acyl-2-aminothiazoles | |
| NO312726B1 (en) | Enterokinetic benzamide | |
| CN107501251A (en) | A kind of compound and its application in Claritin is prepared | |
| CN107501258B (en) | A kind of thiazolyl nicotinamide compound and its application in preparing antiallergy and asthmatic medicament | |
| CN101641350A (en) | Dibenzo [b, f] [1,4] oxaaza compounds | |
| CN113307791A (en) | Pyrimidylpiperazine urea TRPV1 antagonistic/MOR agonistic double-target compound and preparation method and application thereof | |
| CN107400124A (en) | A kind of nicotinamide compound, synthetic route and its application in Claritin is prepared | |
| DE69807523T2 (en) | CARBOXYL-SUBSTITUTED CHROMANE DERIVATIVES FOR USE AS BETA 3 ADRENORE RECEPTOR AGONISTS | |
| CN107522694A (en) | A kind of nicotinamide compound, synthetic route and its application in antiallergy and asthmatic medicament is prepared | |
| CN107573337A (en) | A kind of compound, preparation method and its application in treatment allergy and asthmatic medicament is prepared | |
| DE60005368T2 (en) | Thienopyran-carboxamide DERIVATIVES | |
| CN104788423B (en) | A kind of new cystic fibrosis transmembrane conductance regulator inhibitor | |
| CN107793350A (en) | Fragrant ethyl piperidine radical derivative and its schizoid application for the treatment of |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180720 |