- Evaluating the Viability of Successive Ring-Expansions Based on Amino Acid and Hydroxyacid Side-Chain Insertion
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The outcome of ring-expansion reactions based on amino/hydroxyacid side-chain insertion is strongly dependent on ring size. This manuscript, which builds upon our previous work on Successive Ring Expansion (SuRE) methods, details efforts to better define the scope and limitations of these reactions on lactam and β-ketoester ring systems with respect to ring size and additional functionality. The synthetic results provide clear guidelines as to which substrate classes are more likely to be successful and are supported by computational results, using a density functional theory (DFT) approach. Calculating the relative Gibbs free energies of the three isomeric species that are formed reversibly during ring expansion enables the viability of new synthetic reactions to be correctly predicted in most cases. The new synthetic and computational results are expected to support the design of new lactam- and β-ketoester-based ring-expansion reactions.
- Lawer, Aggie,Epton, Ryan G.,Stephens, Thomas C.,Palate, Kleopas Y.,Lodi, Mahendar,Marotte, Emilie,Lamb, Katie J.,Sangha, Jade K.,Lynam, Jason M.,Unsworth, William P.
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supporting information
p. 12674 - 12683
(2020/09/17)
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- SUBSTITUTED PHENYLOXAZOLIDINONES FOR ANTIMICROBIAL THERAPY
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The present invention relates to novel oxazolidinones (Formula I): or a pharmaceutically acceptable salt having ring A characterized by N-containing monocyclic, bicyclic or spirocyclic substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.
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Page/Page column 28; 29
(2017/02/09)
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- AZEPANE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS
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Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.
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Paragraph 0777; 0778; 0779
(2015/07/22)
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- AZEPANE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS
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Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.
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Paragraph 0774
(2015/09/22)
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- FUSED TRICYCLIC COMPOUNDS FOR USE AS INHIBITORS OF JANUS KINASES
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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 110
(2013/03/26)
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- 1-(DIHYDRONAPHTHALENYL)PYRIDONES AS MELANIN-CONCENTRATING HORMONE RECEPTOR 1 ANTAGONISTS
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Provided are 1-(dihydronaphthalenyl)pyridones which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), pharmaceutical compositions containing them, processes for their preparation, and their use in therapy for the treatment of obesity and diabetes.
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Page/Page column 59
(2013/10/22)
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- HETEROCYCLIC COMPOUND
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The present invention provides to a compound having melanin-concentrating hormone receptor antagonistic action and low toxicity, and useful as a agent for the prophylaxis or treatment of obesity and the like. The present invention relates to a compound re
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Page/Page column 51-52
(2010/12/30)
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- Kinase inhibitor compounds
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The invention relates to compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds, compositions, and methods described herein can be used for the therapeutic modulation of kinase-mediated processes, and treatment of disease and disease symptoms, particularly those mediated by certain kinase enzymes.
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Page/Page column 20; 21
(2009/04/24)
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- NOVEL COMPOUNDS
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The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds according to formula (I) and salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular IKK2 activity.
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Page/Page column 62
(2009/10/22)
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- PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS
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The present invention relates to phosphodiesterase (PDE) type 4, phosphodiesterase (PDE) type 7 and dual PDE type 4 /PDE type 7 inhibitors. Compounds disclosed hereinf having the structure of Formula 1: can be useful in the treatment, prevention, inhibiti
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Page/Page column 52
(2008/12/07)
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- PYRAZOLO (3, 4-B) PYRIDINE DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS
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The present invention relates to phosphodiesterase (PDE) type 4, phosphodiesterase (PDE) type 7 and dual PDE type 4 /PDE type 7 inhibitors. Compounds disclosed herein having the structure of Formura 1: can be useful in the treatment, prevention, inhibitio
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Page/Page column 75
(2008/12/07)
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- KINASE INHIBITOR COMPOUNDS
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The invention relates to compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds, compositions, and methods described herein can be used for the therapeutic modulation of kinase-mediated processes, and treatment of disease and disease symptoms, particularly those mediated by certain kinase enzymes.
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Page/Page column 48
(2008/06/13)
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- THIAZOLE DERIVATIVE
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An adenosine A2A receptor antagonist comprising, as an active ingredient, a thiazole derivative represented by the general formula (I) [wherein R1 represents a substituted or unsubstituted 5-membered aromatic heterocyclic group conta
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Page/Page column 37
(2010/11/30)
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- NOVEL COMPOUNDS
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The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds according to formula (I) and salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular IKK2 activity.
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Page/Page column 90
(2009/01/20)
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- PYRAZOLE COMPOUNDS HAVING CANNABINOID RECEPTOR (CB1) ANTAGONIZING ACTIVITY
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The present invention relates to a pyrazole compound having potent CB1-antagonizing activity, having the following formula [I]: wherein R1 and R2 are the same or different and an optionally substituted aryl group etc., R3 is an alkyl group etc., E is one of the following groups of the formula (i) to (iv): Q1 is a single bond, an alkylene group or a group of the formula: -N(R7)-, R7 is a hydrogen atom or an alkyl group, Q2 is a single bond, an oxygen atom or an alkylene group, R4 is a cycloalkyl group, a group of the formula: -N(R5)(R6) etc., one of R5 and R6 is a hydrogen atom or an alkyl group and the other is an alkyl group, a group of the formula: -N(R8)(R9) etc., D is an oxygen atom etc., RA1 is an amino group etc., RA2 is an optionally substituted aliphatic heterocyclic group, R is an alkyl group optionally substituted by one to three halogen atom(s) etc., one of R8 and R9 is a hydrogen atom or an alkyl group and the other is an alkyl group etc., or a pharmaceutically acceptable salt thereof.
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Page/Page column 118
(2008/06/13)
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- AZOLE COMPOUNDS
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The present invention provides a compound represented by the formula (I) wherein R1 is a hydrogen atom, a halogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxy group, an optionally substituted thiol group or an optionally substituted amino group, A is an optionally substituted cyclic amino group or -NR2-W-D wherein R2 is a hydrogen atom or an alkyl group, W is a bond or a divalent acyclic hydrocarbon group, and D is an optionally substituted cyclic group, an optionally substituted amino group or an optionally substituted acyl group, B is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, X is an oxygen atom, a sulfur atom or an optionally substituted nitrogen atom, and Y is a bond or a divalent acyclic hydrocarbon group, or a salt thereof, which is useful for the prophylaxis or treatment of diabetic neuropathy and the like.
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- Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases
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The preparation and SAR of a series of iNOS inhibitors leading to the most potent compound, incorporating a (1,4)-5-imino thiazepane (R = n-Pr) is disclosed. A series of 3- and 5-imino analogs from oxazepane, thiazepane, and diazepane was prepared and eva
- Shankaran,Donnelly, Karla L.,Shah, Shrenik K.,Caldwell, Charles G.,Chen, Ping,Hagmann, William K.,MacCoss, Malcolm,Humes, John L.,Pacholok, Stephen G.,Kelly, Theresa M.,Grant, Stephan K.,Wong, Kenny K.
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p. 5907 - 5911
(2007/10/03)
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- 6-Substituted pyrido-pyrimidines
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The present invention provides compounds of the Formula I and II: wherein R1, R3, W, Z, X1, X2, Ar1, R8 and R9 are as defined herein, and methods and intermediates for their preparation and uses thereof.
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- Imidazo-substituted compounds as p38 kinase inhibitors
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The present invention discloses compounds corresponding to formula I: wherein A, Z, Z1, Y, R1 and R2 are as defined in the specification, as well as pharmaceutical formulations, methods of making and uses thereof.
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- Hexahydro-5-imino-1,4-1,4-thiazepine derivatives as inhibitors of nitric oxide synthases
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Disclosed herein are compounds of Formula I and pharmaceutically acceptable salts thereof which have been found useful in the treatment of nitric oxide synthase mediated diseases and disorders, including neurodegenerative disorders, disorders of gastrointestinal motility and inflammation. These diseases and disorders include hypotension, septic shock, toxic shock syndrome, hemodialysis, IL-2 therapy such as in in cancer patients, cachexia, immunosuppression such as in transplant therapy, autoimmune and/or inflammatory indications including sunburn, eczema or psoriasis and respiratory conditions such as bronchitis, asthma, oxidant-induced lung injury and acute respiratory distress (ARDS), glomerulonephritis, restenosis, inflammatory sequelae of viral infections, myocarditis, heart failure, atherosclerosis, osteoarthritis, rheumatoid arthritis, septic arthritis, chronic or inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis (SLE), ocular conditions such as ocular hypertension, retinitis and uveitis, type 1 diabetes, insulin-dependent diabetes mellitus and cystic fibrosis.
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- Hexahydro-5-imino-1,4-heteroazepine derivatives as inhibitors of nitric oxide synthases
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Disclosed herein are compounds of Formula I and pharmaceutically acceptable salts thereof which have been found useful in the treatment of nitric oxide synthase mediated diseases and disorders, including neurodegenerative disorders, disorders of gastroint
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- Synthesis and Conformational Analysis of Substituted 4-Aminothianes
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Reductions of substituted 4-thianone oximes by LiAlH4 gave a mixture of epimeric 4-aminothianes.Separation of the epimeric mixture was achieved via column chromatography over neutral alumina.Independent syntheses of these amines by a stereospecific route starting from the tosylate of the corresponding 4-thianols that reacted with sodium azide in DMF followed by reduction of the azide with LiAlH4 provided structure proofs for the amines.N-Acetyl derivatives were also prepared from the aminothianes.Conformational analysis of the amines was performed via an inspection of the (1)H and (13)C NMR spectra.These spectral data suggested t wist conformations for 2,2-dimethyl-trans-6-phenyl-r-4-aminothiane and 2,2-dimethyl-trans-6-p-chlorophenyl-r-4-aminothiane.
- Subramanian, Pullachipatti K.,Ramalingam, Kondareddiar,Satyamurthy, Nagichettiar,Berlin, K. Darrell
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p. 4376 - 4383
(2007/10/02)
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- Neighboring-Group Participation in Organic Redox Reactions: Effect of Tertiary Amine and Pyridine Groups on the Kinetics and Mechanism of Thioether-Sulfoxide Interconversions
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The effect of neighboring tertiary amine, quaternary ammonium, and pyridine substitution on both the oxidation of thioethers by aqueous I2 and the reduction of sulfoxides by aqueous HI has been evaluated.The millionfold acceleration in the rates of the reaction of 5-methyl-1-thia-5-azacyclooctane and its sulfoxide is unique.The rates of the lower homologues and cyclic analogues are not accelerated and at a given acid concentration the rates of oxidation of amine sulfides follow the rate law d/dt=-kox-1.The rates of reduction of the aminesulfoxides follow the rate law d/dt=kred.The pH profiles of the I2 oxidation of 6-methyl-2-thia-6-azaheptane and 2-pyridine demonstrate neighboring-group participation and suggest N-S interacted intermediates.
- Doi, Joyce Takahashi,Musker, W. Kenneth,deLeeuw, David L.,Hirschon, Albert S.
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p. 1239 - 1243
(2007/10/02)
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