- Reaction Rates of Various N-Acylenamines in the Inverse-Electron-Demand Diels–Alder Reaction
-
In light of the bioorthogonal inverse-electron-demand Diels–Alder strategy, an extended investigation into the effects of ring strain and electron inductive effects on the reactivity of the N-acylenamine core towards tetrazine has been carried out. Through a comparative study between N-acylazetines, N-vinylcarbamates and an N-vinylamide it was shown that ring strain has a more significant effect on reaction rate than electron donation. A significantly improved synthetic route is reported for the preparation of an N-acylazetine biorthogonal tag we have invented previously.
- Engelsma, Sander B.,van den Ende, Thomas C.,Overkleeft, Hermen S.,van der Marel, Gijsbert A.,Filippov, Dmitri V.
-
-
Read Online
- RET Inhibitor. Pharmaceutical composition and use thereof
-
The invention belongs to the field of medicines, and relates to RET inhibitor, a pharmaceutical composition and application thereof. , The present invention relates to a compound represented by formula (I), a stereoisomer, a tautomer, an oxynitride, a solvate, a metabolite, a pharmaceutically acceptable salt or prodrug thereof, I, and a pharmaceutical composition thereof in the manufacture of a medicament, in particular for the treatment and prophylaxis of diseases and disorders associated and RET.
- -
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Paragraph 0408-0411
(2021/10/27)
-
- A novel RET inhibitor. Pharmaceutical composition and use thereof
-
The invention belongs to the field of medicines, and relates to a novel RET inhibitor, a pharmaceutical composition and application thereof. In particular, the invention relates to a compound represented by formula (I), a stereoisomer, a tautomer, an oxynitride, a solvate, a metabolite, a pharmaceutically acceptable salt or prodrug thereof, I said compound and a pharmaceutical composition thereof for the manufacture of a medicament, in particular for the treatment and prophylaxis and RET of diseases and disorders associated with irritable bowel syndrome.
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Paragraph 0312-0315
(2021/11/26)
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- BROAD-SPECTRUM CARBAPENEMS
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The present disclosure provides broad-spectrum carbapenem derivatives and pharmaceutical compositions useful in the treatment of bacterial infections and methods for treating such infections using such derivatives and/or compositions.
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Page/Page column 00167
(2021/05/29)
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- PROCESSES OF PREPARING A JAK1 INHIBITOR
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The present application provides processes for preparing 4-[3-(cyanomethyl)-3-(3′,5′-dimethyl-1H, 1′H-4,4′-bipyrazol-1-yl)azetidin-1-yl]-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide, and phosphoric acid salt thereof, which is useful as a selective (Janus kinase 1) JAK1 inhibitor, as well as salt forms and intermediates related thereto.
- -
-
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- ?-LACTAMASE INHIBITOR AND USE THEREOF
-
Provided are a β-lactamase inhibitor of formula (I), or an ester, a stereoisomer or a pharmaceutically acceptable salt thereof, and a method of preparing the same. Further provided is a pharmaceutical composition comprising the β-lactamase inhibitor of formula (I), or the ester, the stereoisomer or pharmaceutically acceptable salt thereof. In addition, the present invention relates to a method for treating diseases caused by bacterial infection, which comprises administering the β-lactamase inhibitor of formula (I), or the ester, the stereoisomer or the pharmaceutically acceptable salt thereof to a patient or a subject in need.
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Paragraph 0211; 0212
(2020/12/10)
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- COMPOUND AS ACC INHIBITOR AND USE THEREOF
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Disclosed are a class of compounds which are inhibitors of acetyl-CoA carboxylase (ACC) and the use thereof. In particular, provided are compounds as shown in formula I or isomers, pharmaceutically acceptable salts, solvates, crystals or prodrugs thereof, and methods for preparing the same, and pharmaceutical compositions comprising the compounds and the use of the compounds or compositions for treating and/or preventing diseases associated with ACC expression, such as fibrotic diseases, metabolic diseases, cancers or tissue hyperplasia diseases. The compound has a good inhibitory activity against ACC and shows good promise to be a therapeutic drug for fibrotic diseases, metabolic diseases, cancers or tissue hyperplasia diseases.
- -
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Paragraph 0279; 0280
(2020/06/15)
-
- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
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Paragraph 00504; 00512; 00521; 00529; 00543; 00556; 00570
(2020/07/06)
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- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
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Paragraph 00230; 00643; 00685
(2020/07/05)
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- PYRROLO(PYRAZOLO)PYRIMIDINE DERIVATIVE AS LRRK2 INHIBITOR
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The present invention relates to a pyrrolo(pyrazolo)pyrimidine derivative having efficacy as an LRRK2 inhibitor, a preparation method therefor, and a pharmaceutical composition for preventing or treating degenerative brain diseases, containing the same.
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Paragraph 0122
(2020/11/23)
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- PROTEIN KINASE INHIBITORS FOR PROMOTING LIVER REGENERATION OR REDUCING OR PREVENTING HEPATOCYTE DEATH
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The invention relates to compounds of formula (I) which are inhibitors of MKK4 (mitogen-activated protein kinase kinase 4) and their use in promoting liver regeneration or reducing or preventing hepatocyte death. The compounds selectively inhibit protein kinase MKK4 over protein kinases JNK and MKK7. (I), wherein R x, R y , R z and R zz are selected from: a) R x and R y are F and R z and R zz are H; b) R x, R y and R zz are independently halogen and R z is H; c) R x R z and R zz are independently halogen and R y is H; and d) R x R y and R z are independently halogen and R zz is H
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Page/Page column 116
(2020/02/14)
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- Compound as well as preparation method and medical application thereof
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The invention provides a compound as well as a preparation method and medical application thereof, the compound has a structure as shown in a general formula (I), and can also be a tautomer, a mesomer, a raceme, an enantiomer, a diastereoisomer, or a mixture form thereof, or a pharmaceutically acceptable salt thereof. According to the compound with the structure as shown in the general formula (I)provided by the invention, a specific main chain structure and a corresponding substituent group are selected, so that the obtained compound can be used as an arginase inhibitor, is relatively high in activity, and has a potential treatment prospect in various diseases.
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Paragraph 0444-0446
(2020/02/14)
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- 3-nitrile methylene azetidine-1-tert-butyl carbonate preparation method
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The invention discloses a 3-nitrile methylene azetidine-1-tert-butyl carbonate preparation method, which specifically comprises: 1, synthesizing 1-tert-butyl-3-glycolate; 2, synthesizing N-Boc-3-hydroxy azetidine through the 1-tert-butyl-3-glycolate obtained in the step 1; 3, synthesizing N-Boc-3-azetidinone through the N-Boc-3-hydroxy azetidinone obtained in the step 2; and 4, synthesizing 3-nitrile methylene azetidine-1-tert-butyl carbonate through the N-Boc-3-azetidinone obtained in the step 3. According to the preparation method disclosed by the invention, the existing conventional five-step synthesis process of 3-nitrile methylene azetidine-1-tert-butyl carbonate is reduced into three steps, so that the synthesis time is greatly saved, the emission of three-waste is reduced, and the process cost is reduced.
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Page/Page column 8; 15-18
(2020/02/06)
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- MERTK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00803; 00804
(2020/01/31)
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- Regioselective α-benzylation of 3-iodoazetidine via Suzuki cross-coupling
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An efficient protocol for the synthesis of α-benzyl azetidines starting from benzylboronic acid pinacol ester derivatives and 3-iodoazetidine was developed. A wide range of α-benzyl azetidine derivatives were obtained in moderate to good yields with high regioselectivity (>99%).
- Qiu, Zhenjiang,Zhu, Mingxiang,Zheng, Lu,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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supporting information
p. 1321 - 1324
(2019/04/25)
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- A 3 - nitro-azetidine -1 - formic acid tert-butyl synthetic method
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The invention relates to a 3 - nitro-azetidine - 1 - carboxylic acid tert-butyl synthetic method, mainly solves the industrial synthesis method not suitable for the technical problem. The invention is divided into three steps, 1st step, first of all by compound 1 in the solvent non-water reaction adding sodium borohydride in methanol to obtain compound 2, 2nd step, compound 2 with imidazole, triphenylphosphine and iodine in toluene in reaction to obtain compound 3, 3rd step, compound 3 with urea, sodium nitrite and phloroglucinol in N, N - dimethyl formamide in reaction to obtain the final compound 4, reaction as follows: .
- -
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Paragraph 0007; 0008
(2019/04/04)
-
- NOVEL SULFONAMIDE CARBOXAMIDE COMPOUNDS
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The present invention relates to compounds of formula (I) wherein Q is selected from O or S; R1 is a non-aromatic heterocyclic group comprising at least one ring nitrogen atom, wherein R1 is attached to the sulfur atom of the sulfonylurea group by a ring carbon atom, and wherein R1 may optionally be substituted; and R2 is a cyclic group substituted at the α-position, wherein R2 may optionally be further substituted. The present invention further relates to salts, solvates and prodrugs of such compounds, to pharmaceutical compositions comprising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by the inhibition of NLRP3.
- -
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Page/Page column 194; 195
(2019/01/21)
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- PROCESSES AND INTERMEDIATES FOR MAKING A JAK INHIBITOR
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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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Paragraph 0111; 0113
(2019/08/22)
-
- Preparation method of N-Boc-3-hydroxyl azetidine
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The invention belongs to the technical field of organic synthesis of solid-phase peptide, and particularly relates to a preparation method of N-Boc-3-hydroxyl azetidine. The preparation method of N-Boc-3-hydroxyl azetidine comprises the steps that 1-(benzhydryl)-3-hydroxyl azetidine serves as a raw material, in the mixed solvent of methyl alcohol and formic acid, palladium carbon serves as a catalyst to conduct a diphenylmethane removal reaction, then di-tert-butyl decarbonate ester is added to conduct a t-butyloxycarbonyl protection reaction, diphenylmethane can be better removed and separated by utilizing the properties of different solvents in the whole reaction process, Boc protection can be conducted in the methanol solution directly, accordingly extraction conducted through conventional column chromatography is avoided, not only is the technology simplified, but also the total yield of the two-step reactions reaches 90% or above, the product purity is as high as 99.5% or above, and the purity and the yield of the reaction product are effectively improved.
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Paragraph 0028; 0029; 0030; 0031; 0032; 0033; 0034; 0035
(2019/01/14)
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- An improved, gram-scale synthesis of protected 3-haloazetidines: Rapid diversified synthesis of azetidine-3-carboxylic acids
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Azetidines are increasingly important heterocycles found in a variety of natural products and pharmaceutical compounds. Protected 3-haloazetidines, widely used and versatile building blocks in medicinal chemistry, have been prepared in a one-pot, gram-scale strain-release reaction of 1-azabicyclo[1.1.0]butane from commercially available starting materials. These intermediates were subsequently used to prepare a series of high value azetidine-3-carboxylic acid derivatives including the first reported synthesis of 1-(tert-butoxy-carbonyl)-3-((trifluoromethyl)thio)azetidine-3-carboxylic acid. (Figure pressented)
- Ji, Youngran,Wojtas, Lukasz,Lopchuk, Justin M.
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p. 195 - 214
(2018/06/27)
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- TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 1006
(2018/05/24)
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- Preparation method of 2-[1-(ethyl sulfonyl)-3-azacyclic butyl] acetonitrile
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The invention relates to the technical field of medical chemistry, and particularly relates to a preparation method of a baricotinib tetratomic ring intermediate, and also provides green oxidizing reaction performed in a micro-channel reactor. According to the method, the raw materials in the technical route are easily obtained; the method is economic, green, environmentally friendly and suitablefor industrial production.
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Paragraph 0072-0074
(2018/11/22)
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- COMPOUNDS
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Disclosed are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis(ALS).
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Page/Page column 309
(2017/02/09)
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- Method for preparing 3-hydroxyazetidine hydrochloride and tert-butyl 3-hydroxyazetidine-1-carboxylate
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The invention discloses a method for preparing 3-hydroxyazetidine hydrochloride and tert-butyl 3-hydroxyazetidine-1-carboxylate and relates to the field of drug synthesis. The method comprises the following steps: taking 3-sustituted-1,2-epoxypropane, a benzaldehyde compound and ammonium hydroxide as initiators so as to obtain a first intermediate with an imine structure; and hydrolyzing the first intermediate so as to obtain hydroxylammonium salt, and performing ring closing, thereby obtaining the target product. On the basis of the preparation method, two different synthetic strategies of sequentially performing ring closing and introducing a Boc group and sequentially introducing the Boc group and performing ring closing are respectively adopted from the hydroxylammonium salt, and then tert-butyl 3-hydroxyazetidine-1-carboxylate is prepared at high efficiency. According to the previous three preparation methods, the harsh conditions that a Pd/C catalyst and hydrogen are used and the like are avoided, and extra process steps are avoided. The whole process flow is reasonable in design, and the method is mild in conditions, simple and convenient to operate, readily available in raw materials, high in production efficiency and very suitable for large-scale industrial production.
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Paragraph 0027; 0064; 0065; 0066; 0067; 0068-0073
(2017/08/30)
-
- Pleuromutilin antibiotics
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The present invention relates to pleuromutilin antibiotics represented by a general formula (I), pharmaceutically acceptable salts, prodrugs, solvates or stereoisomers thereof, wherein R, R, R, R, m, X and Y are defined in an instruction. The present invention further relates to preparation methods of the compounds, drug compositions containing the compounds, drug preparations containing the compounds, and applications of the compounds in preparation of drugs for treatment and/or prevention of diseases caused by microorganisms.
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Paragraph 0287-0289
(2017/01/23)
-
- Five-And-Six-Membered Heterocyclic Compound, And Preparation Method, Pharmaceutical Composition And Use Thereof
-
A five-and-six-membered heterocyclic compound as represented by general formula I, pharmaceutically acceptable salt, metabolite, metabolic precursors or drug precursors thereof, preparation method, pharmaceutical composition, and use thereof; the five-and-six-membered heterocyclic compound has activity as a Janus kinase (JAK) inhibitor, and can be used to prepare drugs for treating diseases caused by the abnormal activity of kinase, such as cell proliferation diseases like cancer.
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Paragraph 0353; 0354
(2015/12/07)
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- SUBSTITUTED IMIDAZO[1,2-a]PYRIDINE COMPOUNDS AS TROPOMYOSIN RECEPTOR KINASE A (TrkA) INHIBITORS
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The present application relates to a series of substituted imidazo[1,2-a]pyridine compounds of formula (I), pharmaceutically acceptable salts, pharmaceutically acceptable solvates or stereoisomers thereof, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors, method of making and pharmaceutical compositions comprising such compounds.
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Paragraph 0624; 0625
(2016/01/15)
-
- Development of a Large-Scale Route to an MCH1 Receptor Antagonist: Investigation of a Staudinger Ketene-Imine Cycloaddition in Batch and Flow Mode
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A practical large-scale route to an MCH1 receptor antagonist is described. A Staudinger β-lactam synthesis of an imine and an in situ generated ketene was utilized as a key step for the preparation of a spiro-azetidine building block. The reaction was demonstrated in both batch and flow mode and a comparison of these techniques is described.
- Karlsson, Staffan,Bergman, Rolf,L?fberg, Christian,Moore, Peter R.,Pontén, Fritiof,Tholander, Joakim,S?rensen, Henrik
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p. 2067 - 2074
(2016/01/08)
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- SUBSTITUTED HETEROCYCLIC COMPOUNDS AS TROPOMYOSIN RECEPTOR KINASE A (TRKA) INHIBITORS
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The present application relates to a series of substituted pyrazolo[1,5-a]pyridine compounds, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors, method of making and pharmaceutical compositions comprising such compounds.
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Paragraph 0631 - 0633
(2015/02/05)
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- SUBSTITUTED PYRAZOLES AS N-TYPE CALCIUM CHANNEL BLOCKERS
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Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein R1, R2, ring A, and G are defined herein.
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Page/Page column 58; 59
(2014/03/22)
-
- PROCESSES AND INTERMEDIATES FOR MAKING A JAK INHIBITOR
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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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Paragraph 0155
(2014/09/29)
-
- Design, synthesis, and evaluation of nonretinoid retinol binding protein 4 antagonists for the potential treatment of atrophic age-related macular degeneration and stargardt disease
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Accumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina. Compounds antagonizing the retinol-dependent interaction of retinol-binding protein 4 (RBP4) with transthyretin in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid formation. We recently showed that A1120 (3), a potent carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin bisretinoid formation in the retinas of Abca4-/-mice. As part of the NIH Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained RBP4 antagonists with improved potency and metabolic stability. We also demonstrate that upon acute and chronic dosing in rats, 43, a potent cyclopentyl fused pyrrolidine antagonist, reduced circulating plasma RBP4 protein levels by approximately 60%.
- Cioffi, Christopher L.,Dobri, Nicoleta,Freeman, Emily E.,Conlon, Michael P.,Chen, Ping,Stafford, Douglas G.,Schwarz, Daniel M. C.,Golden, Kathy C.,Zhu, Lei,Kitchen, Douglas B.,Barnes, Keith D.,Racz, Boglarka,Qin, Qiong,Michelotti, Enrique,Cywin, Charles L.,Martin, William H.,Pearson, Paul G.,Johnson, Graham,Petrukhin, Konstantin
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p. 7731 - 7757
(2015/01/09)
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- AZETIDINE DERIVATIVES AS ANTIPARASITIC AGENTS
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This invention recites substituted azetidine derivatives of Formula (1) stereoisomers thereof, veterinarily acceptable salts thereof, compositions thereof, and their use as a parasiticide in animals. The substituents A, B, R1a, R1b, R1c, R2, R3, R4, R6, and n are as described herein.
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Page/Page column 53
(2013/12/03)
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- PROCESS FOR THE PREPARATION OF CHIRAL ISOXAZOLINE AZETIDINE DERIVATIVES AS ANTIPARASITIC AGENTS
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The invention recites a chiral process for the synthesis of isoxazoline azetidine phenyl substituted derivatives of Formula (1) stereoisomers thereof, veterinarily acceptable salts thereof, processes for making, and their use as a parasiticide in an animal. The variables *, R1a, R1b, R1c, R2, and R3 are as described herein
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Page/Page column 28
(2013/08/15)
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- 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 27
(2013/03/26)
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- ISOXAZOLINE DERIVATIVES AS ANTIPARASITIC AGENTS
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This invention recites isoxazoline substituted azetidine derivatives of Formula (1) stereoisomers thereof, veterinarily acceptable salts thereof, compositions thereof, and their use as a parasiticide in mammals and birds. R1a, R1b, R1c, R2, R3, R4, R6, and n are as described herein.
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Paragraph 0620; 0621
(2013/03/26)
-
- Novel carboxamide-based allosteric MEK inhibitors: Discovery and optimization efforts toward XL518 (GDC-0973)
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The ERK/MAP kinase cascade is a key mechanism subject to dysregulation in cancer and is constitutively activated or highly upregulated in many tumor types. Mutations associated with upstream pathway components RAS and Raf occur frequently and contribute to the oncogenic phenotype through activation of MEK and then ERK. Inhibitors of MEK have been shown to effectively block upregulated ERK/MAPK signaling in a range of cancer cell lines and have further demonstrated early evidence of efficacy in the clinic for the treatment of cancer. Guided by structural insight, a strategy aimed at the identification of an optimal diphenylamine-based MEK inhibitor with an improved metabolism and safety profile versus PD-0325901 led to the discovery of development candidate 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S) -piperidin-2-yl]azetidin-3-ol (XL518, GDC-0973) (1). XL518 exhibits robust in vitro and in vivo potency and efficacy in preclinical models with sustained duration of action and is currently in early stage clinical trials.
- Rice, Kenneth D.,Aay, Naing,Anand, Neel K.,Blazey, Charles M.,Bowles, Owen J.,Bussenius, Joerg,Costanzo, Simona,Curtis, Jeffry K.,Defina, Steven C.,Dubenko, Larisa,Engst, Stefan,Joshi, Anagha A.,Kennedy, Abigail R.,Kim, Angie I.,Koltun, Elena S.,Lougheed, Julie C.,Manalo, Jean-Claire L.,Martini, Jean-Francois,Nuss, John M.,Peto, Csaba J.,Tsang, Tsze H.,Yu, Peiwen,Johnston, Stuart
-
supporting information; experimental part
p. 416 - 421
(2012/06/30)
-
- FUSED HETEROCYCLIC COMPOUND
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The present invention relates to a fused heterocyclic compound having the Formula 1, which is useful as a platelet aggregation inhibitor, a method for preparing the same, and a pharmaceutical composition for inhibiting platelet aggregation comprising the same.
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Page/Page column 55
(2011/07/29)
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- 10A-AZALIDE COMPOUND HAVING 4-MEMBERED RING STRUCTURE
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A 10a-azalide compound having a 4-membered ring structure crosslinked at the 10a- and 12-positions, which is represented by the formula (I), and is effective on even Haemophilus influenzae, or erythromycin resistant bacteria (e.g., resistant pneumococci and streptococci).
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Page/Page column 52
(2011/04/14)
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- HEPATITIS C INHIBITOR COMPOUNDS
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Compounds of Formula (I) wherein R1, R2, R3, R4 and R5 are defined herein, maintain good activity against NS3 proteases containing clinically relevant genotype 1a R155K and genotype 1b D168V resistance mutations. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.
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Page/Page column 50
(2011/06/23)
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- CARBAPENEM ANTIBACTERIALS WITH GRAM-NEGATIVE ACTIVITY
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The present invention provides β-methyl carbapenem compounds and pharmaceutical compositions useful in the treatment of bacterial infections and methods for treating such infections using such compounds and/or compositions. The invention includes administering an effective amount of a carbapenem compound or salt and/or prodrug thereof to a host in need of such a treatment.
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Page/Page column 76
(2012/01/06)
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- NUCLEAR TRANSPORT MODULATIORS AND USES THEREOF
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The invention generally relates to the field of nuclear transport modulators, e.g., CRM1 inhibitors, and more particularly to new substituted-heterocyclic azole compounds, the synthesis and use of these compounds and their pharmaceutical compositions, e.g
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Page/Page column 138-139; 214
(2011/10/03)
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- Regio- and stereoselective biohydroxylations with a recombinant escherichia coli expressing P450pyr monooxygenase of sphingomonas Sp. HXN-200
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A recombinant Escherichia coli expressing P450pyr monooxygenase of Sphingomonas sp. HXN-200 was developed as a useful biocatalyst for regio- and stereoselective hydroxylations, with no side reaction and easy cell growth. The resting E. coli cells showed an activity of 4.1 U/g cdw and 9.9 U/g cdw for the hydroxylation of N-benzylpyrrolidin-2-one 1 and N-benzyloxycarbonylpyrrolidine 3, respectively, being as active as the wide-type strain. Biohydroxylation of N-benzylpyrrolidin-2-one 1 with the resting cells gave (S)-N-benzyl-4- hydroxypyrrolidin-2-one 2 in >99% ee and 10.8 mM, a 2.6 times increase of product concentration in comparison with the wild-type strain. Biohydroxylation of N-tert-butoxycarbonylpiperidin-2-one 5, N-benzylpiperidine 7 and N-tert-butoxycarbonylazetidine 9 with the E. coli cells afforded the corresponding 4-hydroxypiperidin-2-one 6, 4-hydroxypiperidine 8, and 3-hydroxyazetidine 10 in 14 mM, 17 mM, and 21 mM, respectively. Moreover, hydroxylation of (-)-β-pinene 11 with the recombinant E. coli cells showed excellent regio- and stereoselectivity and gave (1R)-trans-pinocarveol 12 in 82% yield and 4.1 mM, which is over 200 times higher than that obtained with the best biocatalytic system known thus far. The recombinant strain was also able to hydroxylate other types of substrates with unique selectivity: biohydroxylation of norbornane 13 gave exo-norbornaeol 14, with exo/endo selectivity of 95%; tetralin 15 and 6-methoxytetralin 17 were hydroxylated at the non-activated 2-position, for the first time, with regioselectivities of 83-84%. Copyright
- Zhang, Wei,Tang, Weng Lin,Wang, Zunsheng,Li, Zhi
-
experimental part
p. 3380 - 3390
(2011/02/23)
-
- Pleuromutilin derivatives having a purine ring. Part 2: Influence of the central spacer on the antibacterial activity against Gram-positive pathogens
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Structural modification of the 4-piperidinethio moiety, as a spacer of the first pleuromutilin analogues 2A and 2B having a purine ring, led to discovery of the novel pleuromutilin derivatives 14B and 17B. These compounds with good solubility in water showed promising in vitro antibacterial activity against various Gram-positive bacteria including MRSA, PRSP, and VRE and have potent in vivo efficacy.
- Hirokawa, Yoshimi,Kinoshita, Hironori,Tanaka, Tomoyuki,Nakamura, Takanori,Fujimoto, Koichi,Kashimoto, Shigeki,Kojima, Tsuyoshi,Kato, Shiro
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scheme or table
p. 170 - 174
(2009/05/07)
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- AZETIDINE AND CYCLOBUTANE DERIVATIVES AS JAK INHIBITORS
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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 62-63
(2009/09/28)
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- ORGANIC COMPOUNDS
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The present invention provides a compound of formula (I): wherein the variants R1, R2, R3, R4, R5, R6, R7 are as defined herein, and wherein said compound is an inhibitor of CETP, and thus can be employed for the treatment of a disorder or disease mediated by CETP or responsive to the inhibition of CETP.
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Page/Page column 76
(2009/05/28)
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- MODULATION OF PROTEIN TRAFFICKING
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Compounds and compositions are provided for treatment or amelioration of one or more disorders characterized by defects in protein trafficking. A method of treating a disorder characterized by impaired protein trafficking includes administering to a subject or contacting a cell with a compound of Formula I: [formula here] or pharmaceutically acceptable salts or derivatives thereof.
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Page/Page column 217-218
(2009/06/27)
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- QUINOLINE COMPOUNDS SUITABLE FOR TREATING DIDORDERS THAT RESPOND TO MODULATION OF THE SEROTONIN 5-HT6 RECEPTOR
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The present invention relates to novel quinoline compounds. The compounds possess valuable therapeutic properties and are particularly suitable, for treating diseases that respond to modulation of the serotonin 5-HT6 receptor. formula (I) where
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Page/Page column 37
(2008/12/04)
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- METHOD AND COMPOSITIONS FOR TREATING HIV INFECTIONS
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Described herein are compounds and compositions that are useful in the treatment of HIV, AIDS, and AIDS-related diseases. In addition, compounds are described herein that are capable of inhibiting the dimerization of HIV proteases.
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Page/Page column 42
(2008/12/08)
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- Novel analogues of istaroxime, a potent inhibitor of Na+,K +-ATPase: Synthesis and structure-activity relationship
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We report the synthesis and biological properties of novel inhibitors of the Na+,K+-ATPase as positive inotropic compounds. Following our previously described model from which Istaroxime was generated, the 5α,14α-androstane skeleton was used as a scaffold to study the space around the basic chain of our lead compound. Some compounds demonstrated higher potencies than Istaroxime on the receptor and the (E)-3-[(R)-3- pyrrolidinyl]oxime derivative, 15, was the most potent; as further confirmation of our model, the E isomers of the oxime are more potent than the Z form. The compounds tested in the guinea pig model induced positive inotropic effects, which are correlated to the in vitro inhibitory potency on the Na +,K+-ATPase. The finding that all tested compounds resulted less proarrhythmogenic than digoxin, a currently clinically used positive inotropic agent, suggests that this could be a feature of the 3-aminoalkyloxime derivative class of 5α,14α-androstane.
- Gobbini, Mauro,Armaroli, Silvia,Banfi, Leonardo,Benicchio, Alessandra,Carzana, Giulio,Fedrizzi, Giorgio,Ferrari, Patrizia,Giacalone, Giuseppe,Giubileo, Michele,Marazzi, Giuseppe,Micheletti, Rosella,Moro, Barbara,Pozzi, Marco,Scotti, Piero Enrico,Torri, Marco,Cerri, Alberto
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supporting information; experimental part
p. 4601 - 4608
(2009/06/06)
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