- Compound as protein degradation agent and preparation method and medical application thereof
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The invention discloses a compound serving as a protein degrading agent and a preparation method and medical application thereof, and particularly discloses a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof, and the
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- Structure-Based Design of Dual-Acting Compounds Targeting Adenosine A2AReceptor and Histone Deacetylase as Novel Tumor Immunotherapeutic Agents
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Adenosine is an immunosuppressive factor in the tumor microenvironment mainly through activation of the A2A adenosine receptor (A2AR), which is a mechanism hijacked by tumors to escape immune surveillance. Small-molecule A2AR antagonists are being evaluat
- Yan, Wenzhong,Ling, Lijun,Wu, Yiran,Yang, Kexin,Liu, Ruiquan,Zhang, Jinfeng,Zhao, Simeng,Zhong, Guisheng,Zhao, Suwen,Jiang, Hualiang,Xie, Chengying,Cheng, Jianjun
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p. 16573 - 16597
(2021/12/02)
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- Access to Trisubstituted Fluoroalkenes by Ruthenium-Catalyzed Cross-Metathesis
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Although the olefin metathesis reaction is a well-known and powerful strategy to get alkenes, this reaction remained highly challenging with fluororalkenes, especially the Cross-Metathesis (CM) process. Our thought was to find an easy accessible, convenient, reactive and post-functionalizable source of fluoroalkene, that we found as the methyl 2-fluoroacrylate. We reported herein the efficient ruthenium-catalyzed CM reaction of various terminal and internal alkenes with methyl 2-fluoroacrylate giving access, for the first time, to trisubstituted fluoroalkenes stereoselectively. Unprecedent TON for CM involving fluoroalkene, up to 175, have been obtained and the reaction proved to be tolerant and effective with a large range of olefin partners giving fair to high yields in metathesis products. (Figure presented.).
- Nouaille, Augustin,Pannecoucke, Xavier,Poisson, Thomas,Couve-Bonnaire, Samuel
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supporting information
p. 2140 - 2147
(2021/03/06)
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- Preparation method of pemetrexed acid
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Belonging to the technical field of organic compound synthesis, the invention in particular relates to a preparation method of pemetrexed acid. The method is characterized by utilizing methyl p-formylbenzoate and malonic acid as the starting materials to synthesize the target product. Compared with the methods for synthesis of the compound reported in previous literatures, the method provided by the invention has the advantages of easily available raw materials, low price and no pollution, greatly reduces the production cost, and is suitable for large-scale industrial production. The method isa brand new synthetic route for the compound.
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- Fluorene derivative
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The invention relates to novel fluorene derivatives, which are especially suitable for use in birefringent films with negative optical dispersion, to novel liquid crystal (LC) formulations and polymer films comprising them, and to the use of the fluorene
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Paragraph 0265-0268
(2017/01/12)
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- METHOD FOR PRODUCING ALCOHOL BY HYDROGENATION OF CARBOXYLIC ACID COMPOUND, AND RUTHENIUM COMPLEX FOR USE IN THE PRODUCTION METHOD
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PROBLEM TO BE SOLVED: To provide a method of obtaining an alcohol by efficiently hydrogenating a variety of carboxylic acid compounds under mild conditions using a homogeneous catalyst. SOLUTION: The present invention provides a method of hydrogenating a carboxylic acid compound, in the presence of a ruthenium complex represented by RuXnYpZq, in an atmosphere of hydrogen [X is a group represented by the following formula; Y is a phosphine ligand having a substituted/unsubstituted alkyl group or a substituted/unsubstituted aryl group; Z is a ligand other than X and Y; n is 1 or 2; p is an integer of 1-4; q is an integer of 0-2] {R1 is H, a substituted/unsubstituted alkyl group or a substituted/unsubstituted aryl group; A1 and A2 independently represent O, NR4 (R4 is H, a substituted/unsubstituted alkyl group or a substituted/unsubstituted aryl group) or S; m is an integer of 1 or more; a solid line and a dashed line both represent a single bond or a double bond}]. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0133; 0137; 0138
(2017/02/02)
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- METHOD FOR MANUFACTURING ALCOHOL BY HYDROGENATION OF CARBOXYLIC ACID COMPOUND AND ESTER COMPOUND
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PROBLEM TO BE SOLVED: To provide a method for obtaining alcohol by hydrogenation of carboxylic acid compound efficiently by using a homogeneous system catalyst, especially a method for obtaining alcohol by hydrogenation of various carboxylic acid compound and ester compound by the homogeneous system catalyst efficiently even under alleviation condition. SOLUTION: A carboxylic acid compound and/or an ester compound is hydrogenated in a presence of a rhenium complex represented by ReXmYnZp, where X is a halogen atom, Y is same or different and each a ligand containing one or more phosphorus atom, Z is a ligand other than X and Y, m is an integer of 1 to 6, p is an integer of 0 to 2 and the sum of m, n and p is an integer of 2 to 6, and a specific alkali metal salt. COPYRIGHT: (C)2015,JPOandINPIT
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Paragraph 0117; 0118; 0127; 0129; 0132
(2016/10/10)
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- Novel Pyrazolo[1,5-a]pyrimidines as Translocator Protein 18 kDa (TSPO) Ligands: Synthesis, in Vitro Biological Evaluation, [18F]-Labeling, and in Vivo Neuroinflammation PET Images
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A series of novel pyrazolo[1,5-a]pyrimidines, closely related to N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide (2, DPA-714), were synthesized and biologically in vitro evaluated for their potential to bind
- Damont, Annelaure,Médran-Navarrete, Vincent,Cacheux, Fanny,Kuhnast, Bertrand,Pottier, Géraldine,Bernards, Nicholas,Marguet, Frank,Puech, Frédéric,Boisgard, Rapha?l,Dollé, Frédéric
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p. 7449 - 7464
(2015/10/05)
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- NOVEL PYRAZINE AMIDE COMPOUNDS
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The present invention relates to compounds of formula 1 or pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, R4, R5, R6 and X? have the meanings as indicated in the specification, to their use as a medicament, to their use in the treatment of a disease selected from among respiratory diseases or complaints and allergic diseases of the airways, to pharmaceutical composition comprising at least one of said compound or a pharmaceutically acceptable salt thereof, as well as to medicament combinations containing one or more of said compounds or a pharmaceutically acceptable salt thereof.
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Paragraph 0138
(2015/02/25)
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- NOVEL PYRAZINE AMIDE COMPOUNDS
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The present invention relates to compounds of formula 1 or pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, R6 and X- have one of the meanings as indicated in the specification, to their use as a medicament, to their use in the treatment of a disease selected from among respiratory diseases or complaints and allergic diseases of the airways, to pharmaceutical composition comprising at least one of said compound or a pharmaceutically acceptable salt thereof, as well as to medicament combinations containing one or more of said compounds or a pharmaceutically acceptable salt thereof.
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Page/Page column 38
(2015/02/25)
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- 5-Substituted isoquinoline derivatives
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A compound represented by the following formula (1) or a salt thereof: wherein R1 represents hydrogen atom, a halogen atom and the like; R2 represents hydrogen atom, a halogen atom, a C1-6 alkyl group and the like; and R3 represents —O—X—C(A1)(A11)—C(A2)(A2l)—N(A3l)(A3)(X represents propylene group etc., A11 and A21 represent hydrogen atom, or a C1-6 alkyl group, A31 represents a C1-6 alkyl group substituted with hydroxyl group, or hydrogen atom, and A1, A2, and A3 represent hydrogen atom, a C1-6 alkyl group and the like) and the like, which has an inhibitory activity on the phosphorylation of myosin regulatory light chain, and is useful for treatment of diseases relating to contraction of various cells and the like.
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- EP4 receptor selective agonists in the treatment of osteoporosis
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This invention is directed to EP4 receptor selective prostaglandin agonists of the Formula I, wherein R2, X, Z and Q are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds. This invention is also directed to methods of treating conditions which present with low bone mass, particularly osteoporosis, frailty, an osteoporotic fracture, a bone defect, childhood idiopathic bone loss, alveolar bone loss, mandibular bone loss, bone fracture, osteotomy, bone loss associated with periodontitis, or prosthetic ingrowth in a mammal comprising administering those compounds.
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- Protein structure-based design, synthesis, and biological evaluation of 5-thia-2,6-diamino-4(3H)-oxopyrimidines: Potent inhibitors of glycinamide ribonucleotide transformylase with potent cell growth inhibition
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The design, synthesis, biochemical, and biological evaluation of a novel series of 5-thia-2,6-diamino-4(3H)-oxopyrimidine inhibitors of glycinamide ribonucleotide transformylase (GART) are described. The compounds were designed using the X-ray crystal structure of human GART. The monocyclic 5- thiapyrimidinones were synthesized by coupling an alkyl thiol with 5-bromo- 2,6-diamino-4(3H)-pyrimidinone, 20. The bicyclic compounds were prepared in both racemic and diastereomerically pure forms using two distinct synthetic routes. The compounds were found to have human GART K(i)s ranging from 30 μM to 2 nM. The compounds inhibited the growth of both L1210 and CCRF-CEM cells in culture with potencies down to the low nanomolar range and were found to be selective for the de hove purine biosynthesis pathway. The most potent inhibitors had 2,5-disubstituted thiophene rings attached to the glutamate moiety. Placement of a methyl substituent at the 4-position of the thiophene ring to give compounds 10, 18, and 19 resulted in inhibitors with significantly decreased mFBP affinity.
- Varney, Michael D.,Palmer, Cindy L.,Romines III, William H.,Boritzki, Theodore,Margosiak, Stephen A.,Almassy, Robert,Janson, Cheryl A.,Bartlett, Charlotte,Howland, Eleanor J.,Ferre, Rosanne
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p. 2502 - 2524
(2007/10/03)
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- Synthesis and biological evaluation of a new series of dihydrofolate reductase inhibitors based on the 4-(2,6-diamino-5-pyrimidinyl)alkyl-L-glutamic acid structure
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A novel series of dihydrofolate reductase inhibitors was uncovered during an expansion of the SAR of 5,10-dideazatetrahydrofolic acid, and their biological activity was evaluated. These new analogs do not possess an oxygen at the 4 position and contain a
- Gossett, Lynn S.,Habeck, Lillian L.,Gates, Susan B.,Andis, Sherri L.,Worzalla, John F.,Schultz, Richard M.,Mendelsohn, Laurane G.,Kohler, William,Ratnam, Manohar,Grindey, Gerald B.,Shih, Chuan
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p. 473 - 476
(2007/10/03)
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- PYRIMIDINYL-GLUTAMIC ACID DERIVATIVES
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The present invention provides novel pyrimidinyl-glutamic acid derivatives and intermediates thereto. Further provided are methods for inhibiting dihydrofolate reductase in mammals and for treating susceptible neoplasms in mammals, particularly humans.
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- Radical isomerization via intramolecular ipso substitution of aryl ethers: Aryl translocation from oxygen to carbon
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Bromopropyl aryl ethers an converted to 3-arylpropanols under standard radical generating conditions in the presence of tributylstannane and AIBN. This rearrangement involves intramolecular ipso attack of the alkyl radicals which generates spiro cyclohexadienyl radical intermediates.
- Lee, Eun,Lee, Chulbom,Tae, Jin Sung,Whang, Ho Sung,Li, Kap Sok
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p. 2343 - 2346
(2007/10/02)
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- Novel 5-Desmethylene Analogues of 5,10-Dideaza-5,6,7,8-tetrahydrofolic Acid as Potential Anticancer Agents
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The synthesis and biological activity of novel 5-desmethylene analogues of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), a potent antitumor agent presently undergoing clinical trials, are described.These compounds are representative of a new series
- Taylor, Edward C.,Gillespie, Paul,Patel, Mona
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p. 3218 - 3225
(2007/10/02)
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- Alkenoic acid derivatives
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An alkenoic acid derivative of the formula STR1 in which X and Y are identical or different and represent sulfur, sulfoxide, sulfone, an alkylene chain, --SCH2 --, or oxygen or a direct bond, W represents --CH=CH-- or --CH2 --CH2 --, o represents a number 1 to 5, A and B are identical or different and represent carboxyl, carboxymethylene, tetrazolyl or tetrazolylmethylene, or --CO2 R9 or --CH2 CO2 R9 or --CONR10 R11 or nitrile n represents a number 1 to 10, m represents a number 0 to 7, T and Z are identical or different and represent oxygen or a direct bond and R2, R3, R8 are identical or different and represent hydrogen, alkyl, alkoxy, halogen, trifluoromethyl, trifluoromethoxy, cyano or nitro and R9 is lower alkyl and R10 and R11 are hydrogen, lower alkyl, alkylsulfonyl or arylsulfonyl or together are an alkylene chain to form a ring and pharmaceutically acceptable salts thereof. Such alkenoic acid derivatives are useful as leucotriene disease antagonists.
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- PHENYL HYDROXAMIC ACIDS INCLUDING A HETERO-CONTAINING SUBSTITUENT
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Phenyl hydroxamic acids are disclosed having the general formula or a pharmaceutically acceptable salt thereof, wherein X is NR, oxygen, sulfur, or a single bond, and Y is NR, oxygen, sulfur, or a single bond, where R can be hydrogen or lower alkyl, g can be 1 or 2, and with the proviso that at least one of X and Y is other than a single bond; Z is aryl, aralkyl or cycloalkyl; R1 is hydrogen, substituted or unsubstituted lower alkyl, cycloalkyl, lower alkenyl or aryl; R2 is hydrogen, lower alkyl, aroyl or acyl; m is 0 to 4 carbon atoms; and, n is 0 to 4 carbon atoms further providing that if one of X or Y is oxygen, the other of X or Y must be oxygen and further that when X and Y are oxygen Z cannot be aralalkyl. These new compounds have been found to be inhibitors or arachidonic acid 5-lipoxygenase and are therefore useful as antiallergy agents and antipsoriatics.
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- Certain arylalkyl or pyridylalkyl hydroxamates useful for treating allergies and asthma
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Arylhydroxamates are provided having the structure STR1 wherein R1 is hydrogen, lower alkyl, aryl, lower alkenyl, cycloalkyl, or aralkyl; R2 is hydrogen, lower alkyl, aryl, cycloalkyl, alkanoyl or aroyl; m is 2 to 8; and STR2 wherein R3 is OH, COOH STR3 These compounds are useful as inhibitors of Δ5 -lipoxygenase and as such are useful as antiallergy agents.
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