CN107573364A - A kind of jak kinase inhibitors - Google Patents
A kind of jak kinase inhibitors Download PDFInfo
- Publication number
- CN107573364A CN107573364A CN201711044130.5A CN201711044130A CN107573364A CN 107573364 A CN107573364 A CN 107573364A CN 201711044130 A CN201711044130 A CN 201711044130A CN 107573364 A CN107573364 A CN 107573364A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- unsubstituted
- substituted
- compound
- 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.)
- Pending
Links
Abstract
The compound represented the invention provides a kind of formula (I) or its pharmaceutically acceptable salt；
Description
Technical field
The present invention relates to pharmaceutical technology field, more particularly to a kind of jak kinase inhibitors.
Background technology
EGFR-TK (tyrosinekinase, TK) can be divided into the receptor type and intracytoplasmic non-receptor type two of cross-film
Kind, extracellular signal is transmitted into the cell by acceptor TK, and non-receptor kinase completes the signal transduction of intracellular.Their major function is all
It is that the phosphate group for being catalyzed ATP γ positions is transferred on the tyrosine residue of protein substrate, by the phosphorylation reaction of target protein,
Protein kinase is changed into activated conformation from inactive conformation, complete the conduction of cell biological signal, make cell to various stimulations
Corresponding reaction is made, is played an important role in regulating cell function.
Receptor tyrosine kinase has multiple types, mainly has EGF-R ELISA (EGFR) family, blood vessel endothelium thin
Intracellular growth factor acceptor (VEGFR) family, PDGF recepter (PDGFR) family, Desmocyte growth factor
Sub- acceptor (FGFR) family and Insulin Receptor Family Insulin Receptor Family etc..
Nonreceptor tyrosine kinase mainly has 10 extended familys, and they play an important role in signal transduction pathway, mainly
Including ABL families, JAK families, SRC families etc..Wherein, JAK is played in the initial step of cytokine signaling to pass
Critical effect.JAK families include 4 members:TYK2、JAK1、JAK2、JAK3.JAK/STAT signal transduction pathways are joined extensively
Propagation, differentiation, apoptosis and process of immune regulation with cell.Found from some researchs over 2005, Janus kinases 2
(JAK2) variation (JAK2V617F) and three polycythemia vera, thrombocythemia and myelofibrosis hematological systems
Disease is related.The immune system diseases associated with inflammation such as the variation of JAK1 and JAK3 kinases and rheumatoid arthritis are relevant.
The content of the invention
It is an object of the invention to a kind of jak kinase inhibitors, to be realized to inflammation, allergic reaction and immunological diseases
More outstanding therapeutic effect.
To achieve the above object, the invention provides one kind the compound or its is pharmaceutically acceptable that following formula (I) represents
Salt；
Wherein, in formula (I)：
A be selected from singly-bound-C (=O)-,-C (=O) O- ,-S (=O)2- ,-C (=O) NH- ,-NH- ,-S (=O) NH- ,-S
(=O)2NH-；
B is selected from C and N；
R is selected from CN, OH, NH2、Me、Et、CF3、CH2CF3、NHCH3、N(CH3)2Or halogen；
R1Selected from H, OH, halogen, substituted C1-C6Alkyl, substituted C1-C6Miscellaneous alkyl, substituted C3-C6Yuan of rings
Alkyl, substituted C3-C6Circle heterocycles alkyl, unsubstituted C1-C6Alkyl, unsubstituted C1-C6Miscellaneous alkyl, unsubstituted C3-C6
First cycloalkyl or unsubstituted C3-C6Circle heterocycles alkyl；
R2And R3Simultaneously or it is respectively selected from H, OH, halogen, substituted C1-C6Alkyl, substituted C1-C6Miscellaneous alkyl,
Substituted C3-C6First cycloalkyl, substituted C3-C6Circle heterocycles alkyl, unsubstituted C1-C6Alkyl, unsubstituted C1-C6It is miscellaneous
Alkyl, unsubstituted C3-C6First cycloalkyl or unsubstituted C3-C6Circle heterocycles alkyl.
Further, the compound or other pharmaceutically acceptable salts of above-mentioned formula I, it is characterised in that for preventative
Or therapeutic suppression immune response.
Further, the compound or other pharmaceutically acceptable salts of above-mentioned formula I, it is characterised in that for suppressing to feed
The immune response of newborn animal.
Meanwhile the invention also discloses a kind of pharmaceutical composition, the compound comprising above-mentioned formula I or its is pharmaceutically acceptable
Salt.
Compared with prior art, the beneficial effects of the invention are as follows：A kind of disclosed jak kinase inhibitors, can
Inflammation, allergic reaction and immunological diseases are realized with more outstanding therapeutic effect.
Embodiment
With reference to each embodiment, the present invention is described in detail, but it should explanation, these embodiments are simultaneously
Non- limitation of the present invention, those of ordinary skill in the art are according in these embodiment institute work energy, method or structures
Equivalent transformation or replacement, belong within protection scope of the present invention.
Unless otherwise specified, the term " room temperature " in each embodiment of this specification is specially 23 DEG C；When term " h " is specially
Between measurement unit：Hour；Term " min " is specially time measurement unit：Minute；Term " ml " is specially volume unit：Milliliter；
Term " L " is specially volume unit：Rise；Term " mol/L " is specially concentration unit.Term " mmol " is specially the amount of material
Unit, i.e., mM；Term " mg " is unit of weight, i.e. milligram.
Pyrrolopyrimidine JAK inhibitor is the primary structure class of current small molecule tyrosine kinase inhibitors drug development
Type, and very big progress is had been achieved for, occupy critical role in the application of the Disease Clinical such as inflammation and organ transplant.
One kind has the compound or its pharmaceutically acceptable salt of following formula (I) expression；
Wherein, in formula (I)：
A be selected from singly-bound-C (=O)-,-C (=O) O- ,-S (=O)2- ,-C (=O) NH- ,-NH- ,-S (=O) NH- ,-S
(=O)2NH-；
B is selected from C and N；
R is selected from CN, OH, NH2、Me、Et、CF3、CH2CF3、NHCH3、N(CH3)2Or halogen；
R1Selected from H, OH, halogen, substituted C1-C6Alkyl, substituted C1-C6Miscellaneous alkyl, substituted C3-C6Yuan of rings
Alkyl, substituted C3-C6Circle heterocycles alkyl, unsubstituted C1-C6Alkyl, unsubstituted C1-C6Miscellaneous alkyl, unsubstituted C3-C6
First cycloalkyl or unsubstituted C3-C6Circle heterocycles alkyl；
R2And R3Simultaneously or it is respectively selected from H, OH, halogen, substituted C1-C6Alkyl, substituted C1-C6Miscellaneous alkyl,
Substituted C3-C6First cycloalkyl, substituted C3-C6Circle heterocycles alkyl, unsubstituted C1-C6Alkyl, unsubstituted C1-C6It is miscellaneous
Alkyl, unsubstituted C3-C6First cycloalkyl or unsubstituted C3-C6Circle heterocycles alkyl.
The compound or other pharmaceutically acceptable salts of above-mentioned formula I, it is immune anti-for preventative or therapeutic suppression
Should.The compound or other pharmaceutically acceptable salts of above-mentioned formula I, for suppressing the immune response of mammal.The present invention is also
A kind of pharmaceutical composition is proposed, includes the compound or its pharmaceutically acceptable salt described in above-mentioned formula (I).The drug regimen
Thing can be the pharmaceutical dosage forms of the other forms such as intravenous injection injection, oral tablet.The pharmaceutical composition can be used for preventative
The either therapeutic disease or the patient's condition relevant with pathology JAK activation.
For example, compound or its pharmaceutically acceptable salt that disclosed formula (I) represents can be used for organ
Rejection caused by transplanting, rheumatic arthritis, rheumatoid arthritis, myotenositis, myocarditis, leucoderma, psoriasis,
The treatment and prevention of the diseases such as vaginitis, enteritis, asthma, tumour.
Meanwhile this specification also discloses a kind of compound of formula (I) expression or the synthesis of its pharmaceutically acceptable salt
Method.The synthetic method is that 9 steps react (i.e. step a~step i), the following institute of reaction equation involved by its synthetic route
Show：
Step a
Dichloromethane 10ml, 2- nitro 5- aminopyridines (200mg, 1.4mmol) starting material 1 is added into 50ml reaction bulbs
2 oxobutyric acid ethyl ester (280ml, 1.4mmol) bromo- with 4-, room temperature magnetic agitation react 1~2h, are concentrated under reduced pressure and remove solvent,
Residue 10ml ethanol, and specially after absolute ethyl alcohol dissolving, 3h is heated to reflux, TLC detection reactions are complete.Reaction solution is naturally cold
But ethanol is removed to being concentrated under reduced pressure after room temperature.Residue is washed with saturated sodium bicarbonate solution, and water layer is extracted with dichloromethane, is had
Machine layer is stayed overnight using anhydrous sodium sulfate drying, is filtered and is concentrated, and residue is separated using silica gel column chromatography, in obtaining yellow solid as
Mesosome 2.MS calculated values 235, measured value 236 [M+1].
Step b
Under normal temperature condition, 150mg intermediates 2 are dissolved in 20ml ethanol (being specially absolute ethyl alcohol), gradually add 2ml concentration
Hydrochloric acid and 15mg platinum dioxides for 1mol/L, nitrogen protection, it is passed through hydrogen (50psi) and reacts 16h in 50 DEG C of magnetic agitations,
TLC detection reactions are complete, reaction solution concentrated half, filter, obtain white solid 120mg, i.e. intermediate 3.MS:210[M+H]+。
Step c
100mg intermediates 3 and 4- chloro- 7- (p-toluenesulfonyl) pyrrolo- [2,3-d] pyrimidine 137mg are dissolved in 5ml
N-butanol, 158mgDIEA (DIPEA) is continuously added, magnetic agitation, is heated to back flow reaction 16h, TLC detection
Reaction is complete, and reaction solution pressurization concentration, residue is diluted with 10ml water, and aqueous phase ethyl acetate extracts 3 times, each 20ml, is associated with
Machine layer is simultaneously stayed overnight to organic layer solution using anhydrous sodium sulfate drying, is filtered, is concentrated under reduced pressure, residue is separated using silica gel column chromatography
(PE:EA=1：2) light yellow solid 68mg, i.e. intermediate 4, yield 32.4%, are obtained.Wherein, PE is petroleum ether, and EA is acetic acid second
Ester.The mixed solution of petroleum ether and ethyl acetate is selected from step c to the eluent used in the separation of residue silica gel column chromatography,
And the mol ratio of eluent petrochina ether and ethyl acetate is 1:2.
Step d
Condition of ice bath, nitrogen protection, 3.1g intermediates 4 and THF (anhydrous tetrahydro furan) are added into 250ml there-necked flasks
120ml, magnetic agitation, NaH about 500mg, insulation reaction 1h is added portionwise, iodomethane about 7.5g is then gradually added dropwise, drips
Finish, warm naturally to room temperature, reaction 1h, TLC detection reaction is complete, adds 10ml saturated ammonium chlorides and extracts reaction of going out, then adds
Frozen water 50ml, extract 3 times, each 50ml, merge organic using by the mixed solution of dichloromethane (DCM) and methanol (MeOH)
Layer, organic layer solution is stayed overnight using anhydrous sodium sulfate drying, filter, filtrate concentration after obtain intermediate 5 be directly used in it is next
Step reaction.Wherein, in step d, mole for the dichloromethane (DCM) in the mixed solution that is extracted and methanol (MeOH)
Than for 3:1.
Step e
Under room temperature condition, intermediate 5 obtained by step d is dissolved in 20ml ethanol solution, adds caustic alcohol 1.0g, insulation
16~20h is stirred, TLC detection reactions are complete, and reaction solution concentration, residue is diluted with 50ml water, layering, water layer dichloromethane
30ml is extracted 3 times, merges organic layer solution, and organic layer solution is stayed overnight using anhydrous sodium sulfate drying, is filtered, and filtrate is dense
Contracting, residue obtain intermediate 6 about using silica gel column chromatography separation (DCM/MeOH=1/1~10/1, mol ratio in eluent)
589mg, yield 58.2%.MS:341[M+H]+。
Step f
Condition of ice bath, 500mg intermediates 6 are dissolved in 10mlTHF, 111mg tetrahydrochysene lithium aluminiums are added portionwise, risen naturally after adding
Warm to room temperature reaction 2h, TLC detection reaction to terminate, be cooled to 0 DEG C, add frozen water 10ml extractions and go out, filter, water layer DCM/MeOH
(10:1) extract 3 times, each 20ml, merge organic layer anhydrous sodium sulfate drying and stay overnight, filter, filtrate decompression concentration, obtain middle
The crude product of body 7, not purified be directly used in are reacted in next step, MS:299[M+H]+。
Step g
Under normal temperature condition, 150mg intermediates 7 are dissolved in 10ml anhydrous methylene chlorides, add thionyl chloride 300mg, 70 DEG C
Magnetic agitation reacts 1h, and TLC detection reactions are complete, and reaction solution is concentrated under reduced pressure, and obtains intermediate 8, it is straight that the crude product of intermediate 8 is not required to purifying
Connect for reacting in next step.MS:317[M+H]+。
Step h
150mg intermediates 8 are dissolved in 10mlDMSO (dimethyl sulfoxide (DMSO)), 41mg Cymags is added, is warming up to 40 DEG C of reactions
10h, TLC detect reaction completely, are naturally cooling to room temperature, add 10ml frozen water extraction and go out, solution dichloromethane extraction 2 times, often
Secondary 20ml, merge organic layer, and use organic layer solution saturated brine washing 2 times, each 10ml, then anhydrous sodium sulfate is done
It is dry overnight, filter, filtrate concentration, residue column chromatography, obtain white solid 60mg, i.e. intermediate 9.MS:308[M+H]+。
Step i
500mg racemate intermediates 9 are split by hand-type post, then 35 DEG C of isopropanol recrystallizes to obtain white solid
170mg, target product 10, target product 11 are produced, optical purity is above 99.72%.
Jak1, Jak2, Jak3 kinases external activity are tested
Experiment material
Recombination human source Jak1, Jak2, Jak3 protease is purchased from life technology.LANCE Ultra
ULightTM- Jak1 (Tyr1023) peptide and LANCE Eu-w1024Anti-phosphotyrosine (PT66) are purchased from
PerkinElmer。
Use multi-joint ELIASA Envision (PerkinElmer).
Experimental method
Test compound is subjected to 3 times of concentration gradient dilutions, final concentration of 10 μM are arrived 0.17nM totally 11 concentration, Mei Genong
Spend two multiple holes；Contents of the DMSO in detection is reacted is 1%.
Jak1 enzyme reactions
0.02nM Jak1 protein kinases, 50nM LANCE Ultra ULightTM-Jak1(Tyr1023)peptide,38
Μ m ATP, 50mM HEPES (PH 7.5), 10nM MgCl2,1mM EGTA, 2mM DTT, 0.01%BRIG-35. detection plate is
White Proxiplate 384-Plus plate (PerkinElmer), 90min is reacted at room temperature, reaction system is 10 μ l.
Jak2 enzyme reactions
0.02nM Jak2 protein kinases, 50nM LANCE Ultra ULightTM-Jak1(Tyr1023)peptide,38
Μ m ATP, 50mM HEPES (PH 7.5), 10nM MgCl2,1mM EGTA, 2mM DTT, 0.01%BRIG-35. detection plate is
White Proxiplate 384-Plus plate (PerkinElmer), 90min is reacted at room temperature, reaction system is 10 μ l.
Jak3 enzyme reactions
0.02nM Jak3 protein kinases, 50nM LANCE Ultra ULightTM-Jak1(Tyr1023)peptide,38
Μ m ATP, 50mM HEPES (PH 7.5), 10nM MgCl2,1mM EGTA, 2mM DTT, 0.01%BRIG-35. detection plate is
White Proxiplate 384-Plus plate (PerkinElmer), 90min is reacted at room temperature, reaction system is 10 μ l.
Reaction detection
Add 10 μ l detection reagents into reaction plate, wherein LANCE Eu-w1024 Anti-phosphotyrosine
(PT66) the final concentration of 10mM of final concentration of 2nM, EDTA, 60min, Envision instrument read plates are incubated at room temperature.
Data analysis
Reading is converted into by inhibiting rate (%)=(Min-Ratio)/(Max-Min) × 100% by following equation.4 ginsengs
Curve fit (the inXLFIT5 iDBS of Model 205) measures IC50 data, specifically see the table below.
A≤10nM, 10nM≤B≤100nM, 100nM≤C≤100nM, D ＞ 1000nM
Those listed above is a series of to be described in detail only for feasibility embodiment of the invention specifically
Bright, they simultaneously are not used to limit the scope of the invention, all equivalent implementations made without departing from skill spirit of the present invention
Or change should be included in the scope of the protection.
It is obvious to a person skilled in the art that the invention is not restricted to the details of above-mentioned one exemplary embodiment, Er Qie
In the case of without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, embodiment all should be regarded as exemplary, and be nonrestrictive, the scope of the present invention is by appended power
Profit requires rather than described above limits, it is intended that all in the implication and scope of the equivalency of claim by falling
Change is included in the present invention.
Moreover, it will be appreciated that although the present specification is described in terms of embodiments, not each embodiment is only wrapped
Containing an independent technical scheme, this narrating mode of specification is only that those skilled in the art should for clarity
Using specification as an entirety, the technical solutions in the various embodiments may also be suitably combined, forms those skilled in the art
It is appreciated that other embodiment.
Claims (4)
1. one kind has the compound or its pharmaceutically acceptable salt of following formula (I) expression；
Wherein, in formula (I)：
A be selected from singly-bound-C (=O)-,-C (=O) O- ,-S (=O)2- ,-C (=O) NH- ,-NH- ,-S (=O) NH- ,-S (=O)2NH-；
B is selected from C and N；
R is selected from CN, OH, NH2、Me、Et、CF3、CH2CF3、NHCH3、N(CH3)2Or halogen；
R1Selected from H, OH, halogen, substituted C1-C6Alkyl, substituted C1-C6Miscellaneous alkyl, substituted C3-C6First cycloalkyl,
Substituted C3-C6Circle heterocycles alkyl, unsubstituted C1-C6Alkyl, unsubstituted C1-C6Miscellaneous alkyl, unsubstituted C3-C6Yuan of rings
Alkyl or unsubstituted C3-C6Circle heterocycles alkyl；
R2And R3Simultaneously or it is respectively selected from H, OH, halogen, substituted C1-C6Alkyl, substituted C1-C6Miscellaneous alkyl, taken
The C in generation3-C6First cycloalkyl, substituted C3-C6Circle heterocycles alkyl, unsubstituted C1-C6Alkyl, unsubstituted C1-C6Miscellaneous alkyl,
Unsubstituted C3-C6First cycloalkyl or unsubstituted C3-C6Circle heterocycles alkyl.
2. the compound or other pharmaceutically acceptable salts of the formula I that claim 1 describes, it is characterised in that for preventative
Or therapeutic suppression immune response.
3. the compound or other pharmaceutically acceptable salts of the formula I that claim 1 describes, it is characterised in that for suppressing to feed
The immune response of newborn animal.
4. a kind of pharmaceutical composition, it is characterised in that comprising compound as claimed in claim 1 or its is pharmaceutically acceptable
Salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711044130.5A CN107573364A (en) | 2017-10-31 | 2017-10-31 | A kind of jak kinase inhibitors |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711044130.5A CN107573364A (en) | 2017-10-31 | 2017-10-31 | A kind of jak kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107573364A true CN107573364A (en) | 2018-01-12 |
Family
ID=61040861
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711044130.5A Pending CN107573364A (en) | 2017-10-31 | 2017-10-31 | A kind of jak kinase inhibitors |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107573364A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107602591A (en) * | 2017-10-31 | 2018-01-19 | 无锡福祈制药有限公司 | A kind of JAK3 inhibitor |
| CN107602590A (en) * | 2017-10-31 | 2018-01-19 | 无锡福祈制药有限公司 | Endocyclic compound with Janus kinase inhibiting activities |
| CN107652308A (en) * | 2017-10-31 | 2018-02-02 | 无锡福祈制药有限公司 | A kind of JAK3 inhibitor |
| CN107721988A (en) * | 2017-10-31 | 2018-02-23 | 无锡福祈制药有限公司 | The ketone compounds of iso-indoles 1 with anti-inflammatory activity |
| CN107722006A (en) * | 2017-10-31 | 2018-02-23 | 无锡福祈制药有限公司 | A kind of thalidomide analogs |
| CN107778321A (en) * | 2017-10-31 | 2018-03-09 | 无锡福祈制药有限公司 | A kind of tropsch imatinib analog |
| CN107805259A (en) * | 2017-10-31 | 2018-03-16 | 无锡福祈制药有限公司 | A kind of azolopyrimidines |
| CN110840857A (en) * | 2019-12-20 | 2020-02-28 | 卓和药业集团有限公司 | Medicinal preparation for treating arthritis and preparation method thereof |
| CN112168827A (en) * | 2020-11-03 | 2021-01-05 | 卓和药业集团有限公司 | A pharmaceutical composition for treating psoriasis and preparation method thereof |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105524067A (en) * | 2014-09-28 | 2016-04-27 | 江苏柯菲平医药股份有限公司 | 4-substituted pyrrolo[2,3-d]pyrimidine compound and uses thereof |
| WO2016116025A1 (en) * | 2015-01-20 | 2016-07-28 | 南京明德新药研发股份有限公司 | Jak inhibitor |
| WO2016192563A1 (en) * | 2015-05-29 | 2016-12-08 | 南京明德新药研发股份有限公司 | Janus kinase inhibitor |
| CN107602590A (en) * | 2017-10-31 | 2018-01-19 | 无锡福祈制药有限公司 | Endocyclic compound with Janus kinase inhibiting activities |
| CN107602591A (en) * | 2017-10-31 | 2018-01-19 | 无锡福祈制药有限公司 | A kind of JAK3 inhibitor |
| CN107602537A (en) * | 2017-10-31 | 2018-01-19 | 无锡福祈制药有限公司 | Phthalimide derivative with jak kinase inhibitory activity |
| CN107652308A (en) * | 2017-10-31 | 2018-02-02 | 无锡福祈制药有限公司 | A kind of JAK3 inhibitor |
| CN107778321A (en) * | 2017-10-31 | 2018-03-09 | 无锡福祈制药有限公司 | A kind of tropsch imatinib analog |
| CN107805259A (en) * | 2017-10-31 | 2018-03-16 | 无锡福祈制药有限公司 | A kind of azolopyrimidines |
-
2017
- 2017-10-31 CN CN201711044130.5A patent/CN107573364A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105524067A (en) * | 2014-09-28 | 2016-04-27 | 江苏柯菲平医药股份有限公司 | 4-substituted pyrrolo[2,3-d]pyrimidine compound and uses thereof |
| WO2016116025A1 (en) * | 2015-01-20 | 2016-07-28 | 南京明德新药研发股份有限公司 | Jak inhibitor |
| WO2016192563A1 (en) * | 2015-05-29 | 2016-12-08 | 南京明德新药研发股份有限公司 | Janus kinase inhibitor |
| CN107602590A (en) * | 2017-10-31 | 2018-01-19 | 无锡福祈制药有限公司 | Endocyclic compound with Janus kinase inhibiting activities |
| CN107602591A (en) * | 2017-10-31 | 2018-01-19 | 无锡福祈制药有限公司 | A kind of JAK3 inhibitor |
| CN107602537A (en) * | 2017-10-31 | 2018-01-19 | 无锡福祈制药有限公司 | Phthalimide derivative with jak kinase inhibitory activity |
| CN107652308A (en) * | 2017-10-31 | 2018-02-02 | 无锡福祈制药有限公司 | A kind of JAK3 inhibitor |
| CN107778321A (en) * | 2017-10-31 | 2018-03-09 | 无锡福祈制药有限公司 | A kind of tropsch imatinib analog |
| CN107805259A (en) * | 2017-10-31 | 2018-03-16 | 无锡福祈制药有限公司 | A kind of azolopyrimidines |
Non-Patent Citations (2)
| Title |
|---|
| 支爽等: "吡咯并嘧啶类化合物的合成及其抑制JAK3激酶活性的研究", 《现代药物与临床》 * |
| 王澳轩等: "抑制JAK3激酶的免疫抑制剂托法替尼", 《药物评价研究》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107602591A (en) * | 2017-10-31 | 2018-01-19 | 无锡福祈制药有限公司 | A kind of JAK3 inhibitor |
| CN107602590A (en) * | 2017-10-31 | 2018-01-19 | 无锡福祈制药有限公司 | Endocyclic compound with Janus kinase inhibiting activities |
| CN107652308A (en) * | 2017-10-31 | 2018-02-02 | 无锡福祈制药有限公司 | A kind of JAK3 inhibitor |
| CN107721988A (en) * | 2017-10-31 | 2018-02-23 | 无锡福祈制药有限公司 | The ketone compounds of iso-indoles 1 with anti-inflammatory activity |
| CN107722006A (en) * | 2017-10-31 | 2018-02-23 | 无锡福祈制药有限公司 | A kind of thalidomide analogs |
| CN107778321A (en) * | 2017-10-31 | 2018-03-09 | 无锡福祈制药有限公司 | A kind of tropsch imatinib analog |
| CN107805259A (en) * | 2017-10-31 | 2018-03-16 | 无锡福祈制药有限公司 | A kind of azolopyrimidines |
| CN110840857A (en) * | 2019-12-20 | 2020-02-28 | 卓和药业集团有限公司 | Medicinal preparation for treating arthritis and preparation method thereof |
| CN112168827A (en) * | 2020-11-03 | 2021-01-05 | 卓和药业集团有限公司 | A pharmaceutical composition for treating psoriasis and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107573364A (en) | A kind of jak kinase inhibitors | |
| CN107602591A (en) | A kind of JAK3 inhibitor | |
| CN107652308A (en) | A kind of JAK3 inhibitor | |
| CN107602590A (en) | Endocyclic compound with Janus kinase inhibiting activities | |
| CN107778321A (en) | A kind of tropsch imatinib analog | |
| CA3004372C (en) | Pyrimidine derivative and use thereof | |
| CA2865957C (en) | Compounds for treating spinal muscular atrophy | |
| JP6465996B2 (en) | 3-Acetylenyl-pyrazole-pyrimidine derivative, process for its preparation and its use | |
| TW201706277A (en) | Janus kinase inhibitor | |
| ES2755130T3 (en) | Tricyclic pyrrolopyridine compound, and JAK inhibitor | |
| TW201247665A (en) | Tri- and tetracyclic pyrazolo[3,4-b]pyridine compounds as antineoplastic agent | |
| BRPI1014572B1 (en) | IMIDAZOPIRAZINES FOR USE AS KINASE INHIBITORS | |
| Shiro et al. | 7-Phenyl-imidazoquinolin-4 (5H)-one derivatives as selective and orally available mPGES-1 inhibitors | |
| ES2540962T3 (en) | Azaindole derivatives as inhibitors of Abl and Src protein kinases | |
| CN107602537A (en) | Phthalimide derivative with jak kinase inhibitory activity | |
| CN108276410A (en) | A kind of anaplastic lymphoma kinase inhibitor and its preparation method and application | |
| WO2019182924A1 (en) | Jak inhibitors | |
| JP2018537497A (en) | Pyrido [1,2-a] pyrimidone analogs, their crystalline forms, their intermediates, and methods for their production | |
| JP5822080B2 (en) | Quinoxaline compounds | |
| Ahmed et al. | Exploring the PDE5 H-pocket by ensemble docking and structure-based design and synthesis of novel β-carboline derivatives | |
| Gan et al. | Discovery of novel 4-arylamino-quinazoline derivatives as EGFRL858R/T790M inhibitors with the potential to inhibit the non-small cell lung cancers | |
| Sun et al. | Design, synthesis and biological activity of bicyclic carboxamide derivatives as TRK inhibitors | |
| CN115697988B (en) | 3, 4-Dihydro isoquinoline compound and application thereof | |
| Rao et al. | Discovery of a potent, selective, and covalent ZAP-70 kinase inhibitor | |
| ES2379447T3 (en) | Triazolopyridazines as inhibitors of PAR1, their preparation and their use as medicines |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180112 |