- Copper-Catalyzed Aerobic Oxidative Cyclization Cascade to Construct Bridged Skeletons: Total Synthesis of (?)-Suaveoline
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Based on the discovery of copper-catalyzed cyclopropanol ring-opening addition to iminium ions, an unprecedented catalytic aerobic C?H oxidation/cyclopropanol cyclization cascade using CuCl2 as the multifunctional catalyst and air as the oxidant was developed to construct the azabicyclo[3.3.1]nonane skeleton, which is widespread in natural products and medicines. Using this method, concise asymmetric total synthesis of the indole alkaloid (?)-suaveoline was achieved. This study not only provides an efficient, low-cost, and environmentally benign method for constructing such bridged frameworks, but also enriches the realm of cyclopropanol chemistry and C?H functionalization.
- Tan, Qiuyuan,Yang, Zhao,Jiang, Dan,Cheng, Yuegang,Yang, Jiao,Xi, Song,Zhang, Min
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- FACTOR XIA-INHIBITING PYRIDOBENZAZEPINE AND PYRIDOBENZAZOCINE DERIVATIVES
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The invention relates to substituted pyridobenzazepine and pyridobenzazocine derivatives and to processes for preparation thereof, and also to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and oedemas, and also ophthalmic disorders.
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Paragraph 0567-0569
(2017/10/10)
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- HETEROARYL COMPOUNDS USEFUL AS INHIBITORS OF SUMO ACTIVATING ENZYME
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Disclosed are chemical entities which are compounds of formula (I); or pharmaceutically acceptable salts thereof; wherein Y, Ra, Ra', Rb, Rc, X1, X2, X3, Rd, Z1, and Z2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.
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Paragraph 001019
(2016/01/25)
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- HISTONE DEMETHYLASE INHIBITORS
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Provided herein are substituted pyrazolylpyridine, pyrazolylpyridazine, and pyrazolylpyrimidine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.
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Paragraph 00854; 00855
(2014/06/24)
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- Development of an intramolecular aryne ene reaction and application to the formal synthesis of (±)-crinine
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A general and high yielding annulation strategy for the synthesis of various carbo- and heterocycles, based on an intramolecular aryne ene reaction is described. It was found that the geometry of the olefin is crucial to the success of the reaction, with exclusive migration of the trans-allylic-H taking place. Furthermore, the electronic nature of the aryne was found to be important to the success of the reaction. Deuterium labeling studies and DFT calculations provided insight into the reaction mechanism. The data suggests a concerted asynchronous transition state, resembling a nucleophilic attack on the aryne. This strategy was successfully applied to the formal synthesis of the ethanophenanthridine alkaloid (±)-crinine.
- Candito, David A.,Dobrovolsky, Dennis,Lautens, Mark
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supporting information
p. 15572 - 15580
(2012/11/07)
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- NAPHTHYLACETIC ACIDS
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The invention is concerned with the compounds of formula (I) and pharmaceutically acceptable salts and esters thereof, wherein X, Q, and R1-R6 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are antagonists or partial agonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
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Page/Page column 71-72
(2010/06/15)
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- HETEROCYCLIC DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
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Heterocyclic compounds of structural formula (I), or a pharmaceutically acceptable salt thereof, wherein W is a R1-substituted heteroaryl, R1 is an heteroaryl ring substituted with an ester or carboxylic acid containing radical, X-T is N-CR5R6, C=CR5 or CR13-CR5R6, Y is a bond or -C(O)-, a and b represent an integer selected from 1 to 4, and Ar is an optionally substituted phenyl or naphtyl, are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD) The heterocyclic compounds are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, atherosclerosis, obesity, diabetes, neurological disease, Metabolic Syndrome, insulin resistance, cancer, liver steatosis, and non-alcoholic steatohepatitis.
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Page/Page column 88
(2010/09/17)
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- 6-SUBSTITUTED PHENOXYCHROMAN CARBOXYLIC ACID DERIVATIVES
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Compounds of Formula (I): in which A1, A2, W, L, G, R7a, R7b, R8, R9 and R10 have the meanings given in the specification, are DP2 receptor modulators useful in the treatment of immunologic diseases.
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- Synthesis and structure-activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors
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Botulinum neurotoxins are the most toxic proteins currently known. Based on a recently identified potent lead structure, 2,4-dichlorocinnamic acid hydroxamate, herein we report on the structure-activity relationship of a series of hydroxamate BoNT/A inhibitors. Among them, 2-bromo-4-chlorocinnamic acid hydroxamate, 2-methyl-4-chlorocinnamic acid hydroxamate, and 2-trifluoromethyl-4-chlorocinnamic acid hydroxamate displayed comparable inhibitory activity to that of the lead structure.
- Capkova, Katerina,Yoneda, Yoshiyuki,Dickerson, Tobin J.,Janda, Kim D.
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p. 6463 - 6466
(2008/04/02)
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- 1-(HETERO)ARYL-3-AMINO-PYROLLIDINE DERIVATIVES FOR USE AS MGLUR3 RECEPTOR ANTAGONISTS
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The present invention relates to compounds of the Formula (I) which are useful for treating conditions associated with mGluR3 receptors, such as depression, schizophrenia and migraine, pharmaceutical compositions thereof, and methods of using the same.
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Page/Page column 46-47
(2010/11/08)
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