cas 941685-26-3, 4-CHLORO-7-((2-(TRIMETHYLSILYL)ETHOXY)METHYL)-7H-PYRROLO[2,3-D]PYRIMIDINE

Articles about 941685-26-3Total 37 be found

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AN IMPROVED PROCESS FOR THE PREPARATION OF BARICITINIB
The present invention provides an improved process for the preparation of Baricitinib of formula (I),
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Page/Page column 19

(2021/04/01)

BICYCLIC JAK INHIBITORS AND USES THEREOF
Provided herein are compounds of Formulas (I), (II), (III), and (IV) and subformulas thereof, wherein the variables are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I), (II), (III), or (IV) and methods of using the compounds, e.g., in the treatment of immune disorders, inflammatory disorders, and cancer.
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Paragraph 000187; 000190

(2020/10/20)

Chemical Compounds
The present invention describes novel compounds, or their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their medical uses. The compounds of the invention have activity as Janus Kinase inhibitors and are useful in the treatment or control of pruritus, associated with allergic dermatitis, atopic dermatitis in animals, and other disorders and indications where immunosuppression/immunomodulation would be desirable. Also described herein are methods of treating pruritus and atopic dermatitis by administering the compounds of the invention, which are JAK 1 inhibitors.
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Paragraph 0174; 0175

(2020/05/29)

Small molecular compound
The invention provides a small molecular compound, which is characterized by being a compound shown as the following structure or pharmaceutically acceptable salt thereof, wherein G is a group with aromaticity; X is a nitrogen-containing group; R is a fluorine-containing group; and Cz is connected with a nitrogen atom in the X group. The related compounds have a good performing on inhibiting Jak kinase activity and cytobiological activity.
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Paragraph 0104-0107

(2020/10/29)

Pyrrole/imidazo six-membered hetero-aromatic ring compound as well as preparation method and medical application thereof
The invention relates to a pyrrole/imidazo six-membered hetero-aromatic ring compound as well as a preparation method and medical application thereof. Particularly, the invention relates to a compoundas shown by general formula (I), a preparation method t
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Paragraph 0167-0168; 0171-0172

(2020/07/13)

Pyrrolopyrimidine derivative compound, pharmaceutical composition and application thereof
The invention provides a pyrrolopyrimidine derivative compound as shown in a general formula (I) or a pharmaceutically acceptable salt, a solvate, an active metabolite, a polymorphic substance, an isotope marker, an isomer or a prodrug thereof. The invent
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Paragraph 0109-0111

(2019/07/11)

Pyrrolopyrimidine derivative compound, pharmaceutical composition and application thereof
The invention provides a pyrrolopyrimidine derivative compound as shown in a general formula (I) or a pharmaceutically acceptable salt, a solvate, an active metabolite, a polymorphic substance, an isotope marker, an isomer or a prodrug thereof. The invent
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Paragraph 0090; 0095-0097

(2019/07/11)

SYNTHESIS PROCESS OF RUXOLITINIB
The present application falls within the field of drug synthesis, and in particular, the present application relates to a method for preparing ruxolitinib, and a method for preparing the intermediate and relevant intermediates used. The method comprises reacting a compound of formula II with a compound of formula IV or a salt thereof to obtain a compound of formula III, and then subjecting the compound of formula III to an acyl halogenation reaction, an amidation reaction, and a reaction dehydrating an amide to form a cyano group or removing the protecting group to prepare ruxolitinib. The method has the characteristics of brief steps, a high stereoselectivity, a high utilization ratio of atoms, mild reaction conditions and convenient post treatment. The method avoids using expensive asymmetric reaction catalysts, and is suitable for industrial production.
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Paragraph 0258-0261

(2019/02/05)

PYRROLOPYRIMIDINE CRYSTAL FOR PREPARING JAK INHIBITOR
The present application relates to the field of pharmaceutical chemistry. The application specifically relates to a crystal form A and crystal form B of a pyrrolopyrimidine (formula I) for preparing a JAK inhibitor. The application further relates to a method for preparing the crystal form A and crystal form B, a crystalline composition comprising the crystal form A or crystal form B, a pharmaceutical composition comprising the crystal form A, crystal form B, or crystalline composition, and a pharmaceutical application of the pharmaceutical composition, the crystal form A, and the crystal form B. The crystal form A and crystal form B of the application has the advantages of high purity, high crystallinity, and good stability.
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Paragraph 0075-0076

(2019/05/04)

Preparation Method For Chiral Pyrrolopyrimidine Compound
Provided are a preparation method for a chiral pyrrolopyrimidine compound and a related intermediate. In the method, a compound of formula A and a compound of formula 6 or a salt thereof are reacted to obtain a compound of formula 7 or a compound of formula 14, and a compound of formula I is prepared from the compound of formula 7 or the compound of formula 14. Also provided are the intermediate used, a preparation method for the intermediate and a use of the intermediate in the preparation of the compound of formula I. The preparation method has characteristics such as brief steps, a high stereoselectivity, a high utilization ratio of atoms, mild reaction conditions and a convenient post-treatment. The method avoids using an expensive asymmetric reaction catalyst, and is suitable for industrial production.
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Paragraph 0107-0108

(2019/07/23)

AZETIDINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND USE THEREOF
The present invention relates to an azetidine derivative for use as a Janus kinase (JAK) inhibitor, a drug composition comprising same, a preparation method therefor, and a use thereof in the treatment of JAK-related diseases comprising, for example, infl
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Paragraph 0094; 0095

(2018/08/29)

NEW (HETERO)ARYL-SUBSTITUTED-PIPERIDINYL DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
Compounds of formula (I):wherein R1, R2, J, K, L, n and W are as defined in the description. Medicaments.
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Page/Page column 68

(2018/05/26)

JANUS KINASE 1 SELECTIVE INHIBITOR AND PHARMACEUTICAL USE THEREOF
Janus kinase 1 selective inhibitors and pharmaceutical use thereof are provided.
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Paragraph 0317-0326

(2018/06/07)

BICYCLIC DIAMINES AS JANUS KINASE INHIBITORS
The instant invention provides compounds of formula I which are Jak inhibitors, and as such are useful for the treatment of Jak-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.
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Paragraph 0101

(2019/01/04)

Preparation method for intermediate of Baricitinib
The invention discloses a preparation method for an intermediate of Baricitinib. The intermediate of Baricitinib has a chemical structural formula represented by a formula (I) shown in the description, wherein X is a toluenesulfonate group, a trifluoromethanesulfonate group, chloro-, iodo- or bromo-, and R1 is a group resistant to room-temperature acidic conditions. The preparation method for the intermediate of Baricitinib is characterized by comprising the steps: mixing a compound represented by a formula (II) shown in the description, alkali and a solvent, and carrying out a hydrogen extracting reaction so as to obtain a reaction solution, wherein the alkali is sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, sodium amide or lithium amide; dropwise adding R1Cl into the reaction solution; and carrying out stirring, carrying out a quenching reaction, and carrying out aftertreatment. According to the preparation method, the reaction conditions are mild, the operation is simple, potential risks existing during reactions are greatly reduced, and the disadvantage that mineral oil in sodium hydrogen is not easily detected and the like is overcome. The preparation method is applicable to industrial production and has a very great popularization value.
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Paragraph 0051-0052

(2017/10/13)

Design and Synthesis of Ligand Efficient Dual Inhibitors of Janus Kinase (JAK) and Histone Deacetylase (HDAC) Based on Ruxolitinib and Vorinostat
Concomitant inhibition of multiple oncogenic pathways is a desirable goal in cancer therapy. To achieve such an outcome with a single molecule would simplify treatment regimes. Herein the core features of ruxolitinib (1), a marketed JAK1/2 inhibitor, have been merged with the HDAC inhibitor vorinostat (2), leading to new molecules that are bispecific targeted JAK/HDAC inhibitors. A preferred pyrazole substituted pyrrolopyrimidine, 24, inhibits JAK1 and HDACs 1, 2, 3, 6, and 10 with IC50 values of less than 20 nM, is 100 nM potent against JAK2 and HDAC11, and is selective for the JAK family against a panel of 97 kinases. Broad cellular antiproliferative potency of 24 is supported by demonstration of JAK-STAT and HDAC pathway blockade in hematological cell lines. Methyl analogue 45 has an even more selective profile. This study provides new leads for assessment of JAK and HDAC pathway dual inhibiton achieved with a single molecule.
Yao, Lianbin,Mustafa, Nurulhuda,Tan, Eng Chong,Poulsen, Anders,Singh, Prachi,Duong-Thi, Minh-Dao,Lee, Jeannie X. T.,Ramanujulu, Pondy Murugappan,Chng, Wee Joo,Yen, Jeffrey J. Y.,Ohlson, Sten,Dymock, Brian W.
supporting information
p. 8336 - 8357
(2017/11/03)

PYRROLOPYRIMIDINE COMPOUND
The present application relates to the field of pharmaceutical chemistry, and in particular, to a pyrrolopyrimidine compound represented by general formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. The present invention further relates to a method for preparing the pyrrolopyrimidine compound represented by general formula (I), pharmaceutical compositions and an application of the pyrrolopyrimidine compound in treating diseases mediated by Janus Kinase.
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Paragraph 0122; 0123

(2017/11/11)

Pyrrolopyrimidine compounds containing substituted cyclopentyl group
The invention relates to the field of pharmaceutical chemistry, provides pyrrolopyrimidine compounds containing a substituted cyclopentyl group, and concretely relates to compounds represented by formula A, and stereoisomers and pharmaceutically-acceptable salts thereof. The invention also relates to methods for preparing the pyrrolopyrimidine compounds containing a substituted cyclopentyl group, represented by formula A, a medicinal composition of the compounds, and a use of the compounds in treatment of Janus kinase mediated diseases.
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Paragraph 0082; 0083; 0084; 0085

(2018/01/11)

Pyrrole pyrimidine five-membered nitrogen-heterocyclic derivative and application thereof
The invention relates to a novel JAK (Janus kinase) inhibitor, namely a pyrrole pyrimidine five-membered nitrogen-heterocyclic derivative, and application of the pyrrole pyrimidine five-membered nitrogen-heterocyclic derivative in preparation of a medicine for preventing and/or treating JAK function-related adaptation diseases. The pyrrole pyrimidine five-membered nitrogen-heterocyclic derivative disclosed by the invention is an ideal efficient JAK inhibitor, and can be used for treating or preventing diseases such as rheumatoid arthritis, polycythemia vera, psoriasis, primary thrombocythemia and myelofibrosis.
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Paragraph 0052; 0053; 0054

(2017/07/21)

Preparation method for Baricitinib intermediate
The invention belongs to the field of pharmaceutical and chemical industry, and particularly relates to a preparation method for a Baricitinib intermediate. The preparation method is characterized in that a key intermediate 2-[1-ethyl sulfonyl-3-[4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-parazole-1-ethyl] azacyclobutyl-3-yl) acetonitrile is prepared through reaction of a 4-parazole boride and 2-[1-(ethyl sulfonyl-3-azacyclobutaneylidene) acetonitrile, and nitrogen on a pyrazolone ring of 4- parazole boride does not need to be protected, so that a follow-up step of removing a corresponding a protective group is avoided, and therefore, the whole reaction route is short, raw materials are obtained easier, the production cost is low, and the preparation method is especially suitable for industrial production.
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Paragraph 0123; 0124; 0125

(2017/05/18)

TRIAZOLONE COMPOUNDS AS PERK INHIBITORS
The invention is directed to substituted triazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, X, Y, Y1, and Z are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Str?ussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 68; 69

(2017/04/11)

JAK kinase inhibitor containing 4-aminopyrazole structure, preparation method and application thereof
The invention relates to a JAK kinase inhibitor containing a 4-aminopyrazole structure, a preparation method and an application thereof. Compounds of the series have structures shown in a general formula (I) or a general formula (II). The invention also provides the preparation method of the kinase inhibitor, and the application of the kinase inhibitor in preparation of medicines for preventing or treating inflammation, tumor and blood-related diseases.
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Paragraph 0106; 0107

(2016/10/07)

PROCESSES FOR THE PREPARATION OF RUXOLITINIB PHOSPHATE
The present invention relates to processes for the preparation of ruxolitinib and ruxolitinib phosphate. The present invention also provides a compound of Formula IV, processes for its preparation, and its use for the preparation of ruxolitinib and ruxolitinib phosphate. The present invention provides ruxolitinib phosphate having a chiral purity of 99.96% and the compound of Formula IV having a chiral purity of 99.95%.
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Page/Page column 26

(2016/03/19)

JAK1 INHIBITORS FOR THE TREATMENT OF MYELODYSPLASTIC SYNDROMES
This invention relates to JAK1 selective inhibitors, particularly pyrrolo[2,3-d]pyrimidine and pyrrolo[2,3-b]pyridine derivatives, and their use in treating myelodysplastic syndromes (MDS).
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Paragraph 0132

(2015/10/05)

DEUTERATED BARICITINIB
The present invention in one embodiment provides a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula I are as defined in the specification.
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Paragraph 45

(2014/03/22)

PROCESSES AND INTERMEDIATES FOR MAKING A JAK INHIBITOR
This invention relates to processes and intermediates for making {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, useful in the treatment of diseases related to the activity of Janus kinases (JAK) including inflammatory disorders, autoimmune disorders, cancer, and other diseases.
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Page/Page column 23; 24

(2013/03/26)

FUSED TRICYCLIC COMPOUNDS FOR USE AS INHIBITORS OF JANUS KINASES
The invention provides novel compounds of formula (I) having the general formula (I) wherein R1, V, W, X, Y and Z are as described herein. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment of immunological or hyperproliferative disorders.
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Page/Page column 182-183

(2013/03/26)

PYRROLOPYRIMIDINES AS JANUS KINASE INHIBITORS
The instant invention provides compounds of formula I which are JAK3 inhibitors. Specifically, the compounds of formula I are pyrrolo[2,3-d]pyrimidine derivative compounds. The instant invention also provides methods of treating JAK-mediated diseases such
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Page/Page column 140-141

(2013/06/27)

PYRROLOPYRIMIDINE COMPOUNDS AND USES THEREOF
The present disclosure provides pyrrolopyrimidine compounds and methods of use therefor. For example, the disclosure provides certain pyrrolopyrimidine compounds capable of inhibiting JAK kinases. The disclosure further provides the pharmaceutical compositions containing these pyrrolopyrimidine compounds, and use of these pyrrolopyrimidine compounds in the treatment of disorders or diseases, such as inflammatory diseases and cancer.
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Paragraph 0198; 0199

(2013/08/28)

Targeting conserved water molecules: Design of 4-aryl-5-cyanopyrrolo[2,3-d] pyrimidine Hsp90 inhibitors using fragment-based screening and structure-based optimization
Inhibitors of the Hsp90 molecular chaperone are showing promise as anti-cancer agents. Here we describe a series of 4-aryl-5-cyanopyrrolo[2,3-d] pyrimidine ATP competitive Hsp90 inhibitors that were identified following structure-driven optimization of purine hits revealed by NMR based screening of a proprietary fragment library. Ligand-Hsp90 X-ray structures combined with molecular modeling led to the rational displacement of a conserved water molecule leading to enhanced affinity for Hsp90 as measured by fluorescence polarization, isothermal titration calorimetry and surface plasmon resonance assays. This displacement was achieved with a nitrile group, presenting an example of efficient gain in binding affinity with minimal increase in molecular weight. Some compounds in this chemical series inhibit the proliferation of human cancer cell lines in vitro and cause depletion of oncogenic Hsp90 client proteins and concomitant elevation of the co-chaperone Hsp70. In addition, one compound was demonstrated to be orally bioavailable in the mouse. This work demonstrates the power of structure-based design for the rapid evolution of potent Hsp90 inhibitors and the importance of considering conserved water molecules in drug design.
Davies, Nicholas G.M.,Browne, Helen,Davis, Ben,Drysdale, Martin J.,Foloppe, Nicolas,Geoffrey, Stephanie,Gibbons, Ben,Hart, Terance,Hubbard, Roderick,Jensen, Michael Rugaard,Mansell, Howard,Massey, Andrew,Matassova, Natalia,Moore, Jonathan D.,Murray, James,Pratt, Robert,Ray, Stuart,Robertson, Alan,Roughley, Stephen D.,Schoepfer, Joseph,Scriven, Kirsten,Simmonite, Heather,Stokes, Stephen,Surgenor, Allan,Webb, Paul,Wood, Mike,Wright, Lisa,Brough, Paul
p. 6770 - 6789
(2013/01/15)

PYRROLOPYRIMIDINE COMPOUNDS AND USES THEREOF
Disclosed are pyrrolopyrimidine compounds of formula (I) capable of inhibiting JAK kinase, wherein R1, R2 and m are defined as in the description. The pharmaceutical compositions containing said pyrrolopyrimidine compounds and uses of said pyrrolopyrimidine compounds in the treatment of disorders or diseases such as inflammatory diseases and cancers are also disclosed.
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Page/Page column 31

(2012/03/10)

PYRROLOPYRIMIDINE COMPOUNDS AND USES THEREOF
The present invention provides pyrrolopyrimidine compounds and methods of use therefor. In particular, the invention provides certain pyrrolopyrimidine compounds having the activity of inhibiting JAK kinases. The invention also provides the pharmaceutical compositions containing these pyrrolopyrimidine compounds and use of these compounds in the treatment of inflammatory diseases and cancer.
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Page/Page column 26-27

(2012/03/10)

PIPERIDIN-4-YL AZETIDINE DERIVATIVES AS JAK1 INHIBITORS
The present invention provides piperidin-4-yl azetidine derivatives, as well as their compositions and methods of use, that modulate the activity of Janus kinase 1 (JAK1) and are useful in the treatment of diseases related to the activity of JAK1 including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.
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Page/Page column 37

(2011/10/04)

PROCESSES FOR PREPARING JAK INHIBITORS AND RELATED INTERMEDIATE COMPOUNDS
The present invention is related to processes for preparing chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines of Formula III, and related synthetic intermediate compounds. The chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines are useful as inhibitors of the Janus Kinase family of protein tyrosine kinases (JAKs) for treatment of inflammatory diseases, myeloproliferative disorders, and other diseases.
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Page/Page column 73

(2010/08/07)

Enantioselective synthesis of janus kinase inhibitor INCB018424 via an organocatalytic aza-michael reaction
An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza-Michael addition of pyrazoles (16 or 20) to (E)-3- cyclopentylacrylaldehyde (23) using diarylprolinol silyl ether as the catalyst was developed. Michael adducts (R)-24 and (R)-27 were isolated in good yield and high ee and were readily converted to INCB018424.
Lin, Qiyan,Meloni, David,Pan, Yongchun,Xia, Michael,Rodgers, James,Shepard, Stacey,Li, Mei,Galya, Laurine,Metcalf, Brian,Yue, Tai-N,Liu, Pingli,Zhou, Jiacheng
supporting information; experimental part
p. 1999 - 2002
(2009/09/06)

AZETIDINE AND CYCLOBUTANE DERIVATIVES AS JAK INHIBITORS
The present invention relates to azetidine and cyclobutane derivatives, as well as their compositions, methods of use, and processes for preparation, which are JAK inhibitors useful in the treatment of JAK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.
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Page/Page column 61

(2009/09/28)

PYRROLOPYRIMIDINE DERIVATIVES USED AS HSP90 INHIBITORS
Compounds of formula (I) have HSP90 inhibitory activity and are therefore useful in the treatment of, inter alia, cancer: Formula (I) wherein Ri is hydrogen, fluoro, chloro, bromo, or a radical of formula -X-Alk1-(Z)m-(Alk2)n-Q wherein X is -O-, -S- -S(O)-, -SO2-, or -NH-, Z is -O-, -S-, -(C=O)-, -(C=S)-, -S(O)-, -SO2-, -NRA-, or, in either orientation -C(=O)O-, -C(=O)NRA- , -C(=S)NRA-, -SO2NRA-, -NRAC(=O)-, or -NRASO2- wherein RA is hydrogen or C1-C6 alkyl AIk1 and AIk2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, n and p are independently 0 or 1 , and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is a radical of formula -(Ar1)p-(Alk1)q-(Z)r-(Alk2)s-Q wherein Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1, Alk2, Z, and Q are as defined above, and p, q, r and s are independently 0 or 1 ; and R3 is cyano (-CN), fluoro, chloro, bromo, methyl in which in which one or more hydrogen atoms are optionally replaced by fluorine atoms, ethyl in which in which one or more hydrogen atoms are optionally replaced by fluorine atoms, cyclopropyl, -OH, -CH2OH, -C(O)NH2, -C(O)CH3, Or -NH2.
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Page/Page column 44-45

(2008/06/13)