- One-Pot Generation of Benzynes from Phenols: Formation of Primary Anilines by the Deoxyamination of Phenols
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Benzynes were selectively generated in situ from phenols and trapped regioselectively with potassium hexamethyldisilazide to form primary anilines following acidic workup. The direct conversion of a phenolic hydroxyl group into a free amino group is a useful method for the preparation of primary aryl amines that are hard to synthesize by using coupling reactions involving phenol derivatives with ammonia. Whereas reactions of ortho- and meta-substituted phenols produced meta-substituted anilines exclusively, those of para-substituted phenols provided ortho-silylanilines.
- Akai, Shuji,Ikawa, Takashi,Masuda, Shigeaki
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- INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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Compounds of formula (I') and methods of their use and preparation, as well as compositions comprising compounds of formula (I').
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- INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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The present disclosure is directed to compounds of formula I and methods of their use and preparation, as well as compositions comprising compounds of formula I.
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- Substituted aromatic four ring anti-fungal compound and its preparation method and application
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The invention relates to the technical field of pharmaceuticals, and provides a substituted aryl tetracyclic antifungal compound and pharmaceutically acceptable salts. The substituted aryl tetracyclic antifungal compound is as shown in a structural formula of the description. The invention further provides a preparation method of the compound and an application of the compound in preparing antifungal medicaments.
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- COMPOUNDS AND METHODS FOR TREATING HIV INFECTIONS
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The present invention is directed to novel nanomolar and picomolar inhibitors of HIV reverse transcriptase, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV-1 and HIV-2 and/or secondary disease states and/or conditions which occur as a consequence of HIV infection.
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Paragraph 0378-0380
(2015/04/21)
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- Scaffold hopping of sampangine: Discovery of potent antifungal lead compound against Aspergillus fumigatus and Cryptococcus neoformans
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Discovery of novel antifungal agents against Aspergillus fumigatus and Cryptococcus neoformans remains a significant challenge in current antifungal therapy. Herein the antifungal natural product sampangine was used as the lead compound for novel antifungal drug discovery. A series of D-ring scaffold hopping derivatives were designed and synthesized to improve antifungal activity and water solubility. Among them, the thiophene derivative S2 showed broad-spectrum antifungal activity, particularly for Aspergillus fumigatus and Cryptococcus neoformans. Moreover, compound S2 also revealed better water solubility than sampangine, which represents a promising antifungal lead compound for further structural optimization.
- Jiang, Zhigan,Liu, Na,Dong, Guoqiang,Jiang, Yan,Liu, Yang,He, Xiaomeng,Huang, Yahui,He, Shipeng,Chen, Wei,Li, Zhengang,Yao, Jianzhong,Miao, Zhenyuan,Zhang, Wannian,Sheng, Chunquan
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p. 4090 - 4094
(2014/09/17)
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- Palladium-catalyzed hydroxylation of aryl and heteroaryl halides enabled by the use of a palladacycle precatalyst
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A method for the hydroxylation of aryl and heteroaryl halides, promoted by a catalyst based on a biarylphosphine ligand tBuBrettPhos (L5) and its corresponding palladium precatalyst (1), is described. The reactions allow the cross-coupling of both potassium and cesium hydroxides with (hetero)aryl halides to afford a variety of phenols and hydroxylated heteroarenes in high to excellent yield.
- Cheung, Chi Wai,Buchwald, Stephen L.
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p. 5351 - 5358
(2014/06/23)
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- Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group
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Members of the catechol diether class are highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). The most active compounds yield EC50 values below 0.5 nM in assays using human T-cells infected by wild-type HIV-1. However, these compounds such as rilpivirine, the most recently FDA-approved NNRTI, bear a cyanovinylphenyl (CVP) group. This is an uncommon substructure in drugs that gives reactivity concerns. In the present work, computer simulations were used to design bicyclic replacements for the CVP group. The predicted viability of a 2-cyanoindolizinyl alternative was confirmed experimentally and provided compounds with 0.4 nM activity against the wild-type virus. The compounds also performed well with EC50 values of 10 nM against the challenging HIV-1 variant that contains the Lys103Asn/Tyr181Cys double mutation in the RT enzyme. Indolyl and benzofuranyl analogues were also investigated; the most potent compounds in these cases have EC50 values toward wild-type HIV-1 near 10 nM and high-nanomolar activities toward the double-variant. The structural expectations from the modeling were much enhanced by obtaining an X-ray crystal structure at 2.88 A resolution for the complex of the parent 2-cyanoindolizine 10b and HIV-1 RT. The aqueous solubilities of the most potent indolizine analogues were also measured to be ~40 μg/mL, which is similar to that for the approved drug efavirenz and ~1000-fold greater than for rilpivirine.
- Lee, Won-Gil,Gallardo-Macias, Ricardo,Frey, Kathleen M.,Spasov, Krasimir A.,Bollini, Mariela,Anderson, Karen S.,Jorgensen, William L.
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supporting information
p. 16705 - 16713
(2013/12/04)
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- 9-AZABICYCLO [3 . 3 . 1] NONANE DERIVATIVES AS MONOAMINE REUPTAKE INHIBITORS
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The present invention relates to a 9-azabicyclo[3.3.1]nonane derivative of formula (I), wherein R1 is H or C1-5alkyl; X is O or NR2, wherein R2 is H, C1-5alkyl or C2-5acyl and Ar is C6-10aryl or a 5-10 membered heteroaryl ring system, both being optionally substituted with one to three of R3-R5 independently selected from halogen, C1-5alkyl, C1-5alkoxy, C3-6cycloalkyl, C2-5alkenyl, C2-5alkynyl, CN, NO2, hydroxy, phenyl, phenoxy and phenylC1-2alkoxy, wherein said C1-5alkyl and C1-5alkoxy are optionally substituted with one to three halogens and wherein said phenyl, phenoxy and phenylC1-2alkoxy are optionally substituted with one to three substituents independently selected from halogen and methyl or two of R3-R5 at adjacent positions together form a methylenedioxy or propylene unit, with the proviso that the compounds exo-9-methyl-3-phenoxy-9-azabicyclo[3.3.1]nonane and N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1H indazole-5-amine are excluded, or a pharmaceutically acceptable salt or solvate thereof. The invention also relates to pharmaceutical compositions comprising said 9-azabicyclo[3.3.1]nonane derivatives and to their use in therapy.
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Page/Page column 39
(2010/11/26)
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- 9-Azabicyclo[3.3.1]nonane derivatives
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The present invention relates to a 9-azabicyclo[3.3.1]nonane derivative of formula I, wherein each of the substituents is given the definition as set forth in the specification and claims, or a pharmaceutically acceptable salt or solvate thereof. The invention also relates to pharmaceutical compositions comprising said 9-azabicyclo[3.3.1]nonane derivatives and to their use in therapy.
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Page/Page column 21/1
(2010/11/27)
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- Therapeutic diphenyl ether ligands
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This invention is directed to compounds of formula Ia, Ib or Ic and to pharmaceutical compositions thereof: or a prodrug thereof and a pharmaceutically acceptable carrier, wherein the R groups are defined in the specification; and, in which the dashed line represents an optional double bond. The invention is also directed to methods of treating, diagnosing, and preventing disorders of the central nervous system that are associated with 5HT receptors, including obesity, attention deficit disorder, migraine, depression, epilepsy, anxiety, Alzheimer's disease, withdrawal from drug abuse, pain, schizophrenia, stress-related disorders, panic disorder, sleep disorders, phobias, obsessive compulsive disorder, post-traumatic-stress syndrome, immune system depression, stress-induced gastrointestinal dysfunction, stress-induced cardiovascular dysfunction, and sexual dysfunction.
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Page/Page column 33
(2010/10/20)
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- Studies toward the discovery of the next generation of antidepressants. 3. Dual 5-HT1A and serotonin transporter affinity within a class of N-aryloxyethylindolylalkylamines
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N-Aryloxylethylindolealkylamines (5) having dual 5-HT transporter and 5-HT1A affinity are described. These compounds represent truncated analogues of our previously reported piperidinyl derivatives (3). Compounds in this investigation were found to have more similar affinities and functional activities for the 5-HT1A receptor and 5-HT transporter. Though 5-HT1A antagonism is not consistently observed throughout series 5, several molecular features were found to be essential to obtain high and balanced activities. The proper placement of a heteroatom in the aryl ring and the length of the linkage used to tether the indole moiety had significant influence on 5-HT1A and 5-HT transporter affinities. Introduction of a halogen into the aryl ring usually lowered intrinsic activity and in some cases led to full 5-HT1A antagonists. Compounds 33 and 34 were observed to be full 5-HT1A antagonists with Ki values of approximately 30 nM for the 5-HT1A receptor and Ki values of 5 and 0.5 nM for the 5-HT transporter, respectively. Unfortunately, similar to our previous series (3), compounds in this report also had high affinity for the α1 receptor.
- Mewshaw, Richard E.,Zhou, Dahui,Zhou, Ping,Shi, Xiaojie,Hornby, Geoffrey,Spangler, Taylor,Scerni, Rosemary,Smith, Deborah,Schechter, Lee E.,Andree, Terrance H.
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p. 3823 - 3842
(2007/10/03)
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- SUBSTITUTED 4-ALKOXYOXAZOL DERIVATIVES AS PPAR AGONISTS
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The present invention relates to compounds of formula (I) wherein R1 to R8 and n are as defined in the description and claims, and pharmaceutically acceptable salts and esters thereof. The compounds are useful for the treatment of diseases such as diabetes.
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Page/Page column 27
(2010/02/07)
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- Anilide derivative, production and use thereof
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This invention is to provide a compound of the formula: wherein R1is an optionally substituted 5- to 6-membered ring; the ring A is an optionally substituted 6- to 7-membered ring; the ring B is an optionally substituted benzene ring; n is an integer of 1 or 2; Z is a chemical bond or a divalent group; R2is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula: ?wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium; and R5and R6are independently an optionally substituted hydrocarbon group, an optionally substituted hydroxy group or an optionally substituted amino group, and R5and R6may bind to each other to form a cyclic group together with the adjacent phosphorus atom, or a salt thereof , which is useful for antagonizing CCR5 and also for the prevention and treatment of infectious disease of HIV.
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- Benzofuranyl carbamates
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Compounds of the structure; STR1 and pharmaceutically acceptable salts thereof, wherein: R1 is H, alkyl, alkoxy, carboxyl, alkylcarboxy, trifluoromethyl, halogen, nitro or hydroxy; X is O, N, S or C; Y is O, N or S; and R2 is H, alkyl, cycloalkyl, aryl or heteroaryl useful in the treatment of ischemic heart disease and hypertriglyceridemia.
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