- Design, synthesis and antifungal activity of novel fenfuram-diarylamine hybrids
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Ten novel fenfuram-diarylamine hybrids were designed and synthesized. And their antifungal activities against four phytopathogenic fungi have been evaluated in vitro and most of the compounds demonstrated a significant antifungal activities against Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 5e exhibited the most potent antifungal activity against R. solani with an EC50value of 0.037 mg/L, far superior to the commercially available fungicide boscalid (EC50= 1.71 mg/L) and lead fungicide fenfuram (EC50= 6.18 mg/L). Furthermore, scanning electron microscopy images showed that the mycelia on treated media grew abnormally with tenuous, wizened and overlapping colonies compared to the negative control. Molecular docking studies revealed that compound 5e featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 3-chlorophenyl group in compound 5e formed a CH-π interaction with B/Trp-206 and a Cl-π interaction with D/Tyr-128, rendering compound 5e more active than fenfuram against SDH.
- Wang, Hongyu,Gao, Xuheng,Zhang, Xiaoxiao,Jin, Hong,Tao, Ke,Hou, Taiping
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supporting information
p. 90 - 93
(2016/12/09)
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- Discovery of potent inhibitors of Schistosoma mansoni NAD+ catabolizing enzyme
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The blood fluke Schistosoma mansoni is the causative agent of the intestinal form of schistosomiasis (or bilharzia). Emergence of Schistosoma mansoni with reduced sensitivity to praziquantel, the drug currently used to treat this neglected disease, has underlined the need for development of new strategies to control schistosomiasis. Our ability to screen drug libraries for antischistosomal compounds has been hampered by the lack of validated S. mansoni targets. In the present work, we describe a virtual screening approach to identify inhibitors of S. mansoni NAD+ catabolizing enzyme (SmNACE), a receptor enzyme suspected to be involved in immune evasion by the parasite at the adult stage. Docking of commercial libraries into a homology model of the enzyme has led to the discovery of two in vitro micromolar inhibitors. Further structure-activity relationship studies have allowed a 3-log gain in potency, accompanied by a largely enhanced selectivity for the parasitic enzyme over the human homologue CD38.
- Jacques, Sylvain A.,Kuhn, Isabelle,Koniev, Oleksandr,Schuber, Francis,Lund, Frances E.,Wagner, Alain,Muller-Steffner, Héleìne,Kellenberger, Esther
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p. 3582 - 3592
(2015/05/05)
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- Cu(II)-mediated C-H amidation and amination of arenes: Exceptional compatibility with heterocycles
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A Cu(OAc)2-mediated C-H amidation and amination of arenes and heteroarenes has been developed using a readily removable directing group. A wide range of sulfonamides, amides, and anilines function as amine donors in this reaction. Heterocycles present in both reactants are tolerated, making this a broadly applicable method for the synthesis of a family of inhibitors including 2-benzamidobenzoic acids and N-phenylaminobenzoates.
- Shang, Ming,Sun, Shang-Zheng,Dai, Hui-Xiong,Yu, Jin-Quan
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supporting information
p. 3354 - 3357
(2014/03/21)
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- Complementary regioselectivity in Rh(III)-catalyzed insertions of potassium vinyltrifluoroborate via C-H activation: Preparation and use of 4-trifluoroboratotetrahydroisoquinolones
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Potassium vinyltrifluoroborate was found to be an efficient partner with benzamide derivatives for Rh(III)-catalyzed annulations. 4- Trifluoroboratotetrahydroisoquinolones were generated under mild conditions, affording a regioisomerically complementary substitution pattern to other alkenes in related reactions. These new boron-containing building blocks were derivatized by N-arylations, retaining the boron substituent for further elaboration.
- Presset, Marc,Oehlrich, Daniel,Rombouts, Frederik,Molander, Gary A.
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supporting information
p. 1528 - 1531
(2013/06/27)
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- Pyrazolo[3,4-b]pyridine compounds, and their use as a PDE4 inhibitors
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The invention provides a compound of formula (I) or a salt thereof: wherein R2 is H, C1-3alkyl, n-butyl, C1-2fluoroalkyl, cyclopropyl, cyclobutyl, (cyclopropyl)methyl-, —CN, or —CH2OH; R3 is inter alia optionally substituted C4-7cycloalkyl or an optionally substituted heterocyclic group (aa), (bb) or (cc); Ra is H, methyl or ethyl; Rb is H or methyl; R4 is H, methyl, ethyl, n-propyl, —C(O)-Me, or —C(O)—C1fluoroalkyl; and R5 is: —C(O)—(CH2)n—Ar, —C(O)-Het, —C(O)—C1-6alkyl, —C(O)—C1 fluoroalkyl, —C(O)—(CH2)2—C(O)—NR15bNR15b, —C(O)—CH2—C(O)—NR15bNR15b, —C(O)—NR15b—(CH2)m1—Ar, —C(O)—NR15b—Het, —C(O)—NR15b—C1-6alkyl, —C(O)—NR5aR5b, —S(O)2—(CH2)m2—Ar, —S(O)2-Het, —S(O)2—C1-6alkyl, or —CH2—Ar; or R4 and R5 taken together are —(CH2)p1—, —(CH2)2—X5—(CH2)2—, —C(O)—(CH2)p2—, —C(O)—N(R15)—(CH2)p3—; or NR4R5 is of sub-formula (y), (y1), (y2) or (y3). The invention provides the use of the compounds as inhibitors of phosphodiesterase type IV (PDE4) and/or for the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as COPD and the like.
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Page/Page column 120
(2009/05/28)
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- PYRAZOLO[3,4-B]PYRIDINE COMPOUNDS, AND THEIR USE AS PDE4 INHIBITORS
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The invention provides a compound of formula (I) or a salt thereof: wherein R2 is H, C1-3alkyl, n butyl, C1-2fluoroalkyl, cyclopropyl, cyclobutyl, (cyclopropyl)methyl , CN, or CH2OH; R3 is inter alia optionally substituted C4-7cycloalkyl or an optionally substituted heterocyclic group (aa), (bb) or (cc); Ra is H, methyl or ethyl; Rb is H or methyl; R4 is H, methyl, ethyl, n propyl, C(O) Me, or C(O) C1fluoroalkyl; and R5 is: C(O) (CH2)n Ar, C(O) Het, C(O) C1 6alkyl, C(O) C1fluoroalkyl, C(O) (CH2)2 C(O) NR15bNR15b, C(O) CH2 C(O) NR15bNR15b, C(O) NR15b (CH2)m1 Ar, C(O) NR15b Het, C(O) NR15b C1-6 alkyl, C(O) NR5aR5b, S(O)2 (CH2)m2-Ar, S(O)2 Het, S(O)2-C1-6alkyl, or CH2 Ar; or R4 and R5 taken together are-(CH2)p1-, (CH2)2 X5 (CH2)2 , C(O) (CH2)p2 ,-C(O)-N(R15) (CH2)p3 ; or NR4R5 is of sub-formula (y), (y1), (y2) or (y3). The invention also provides the use of the compounds as inhibitors of phosphodiesterase type IV (PDE4) and/or for the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, allergic rhinitis, psoriasis or atopic dermatitis.
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Page/Page column 187-188
(2010/11/26)
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- Synthesis and biological activity of novel 4,4-difluorobenzazepine derivatives as non-peptide antagonists of the arginine vasopressin V 1A receptor
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To find potent and selective antagonists of the arginine vasopressin (AVP) V1A receptor, optimization studies of compounds structurally related to (Z)-N-{4′-[(4,4-difluoro-5-carbamoylmethylidene-2,3,4,5-tetrahydro-1H- 1-benzazepin-1-yl)carbonyl
- Shimada, Yoshiaki,Taniguchi, Nobuaki,Matsuhisa, Akira,Akane, Hiroaki,Kawano, Noriyuki,Suzuki, Takeshi,Tobe, Takahiko,Kakefuda, Akio,Yatsu, Takeyuki,Tahara, Atsuo,Tomura, Yuichi,Kusayama, Toshiyuki,Wada, Koh-Ichi,Tsukada, Junko,Orita, Masaya,Tsunoda, Takashi,Tanaka, Akihiro
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p. 1827 - 1837
(2007/10/03)
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- USE OF THIOCARBOXANILIDE DERIVATIVES FOR THE PREPARATION OF A MEDICAMENT FOR PREVENTING THE TRANSMISSION OF HIV TO UNINFECTED CELLS AND CONTRACEPTIVE COMPOSITIONS COMPRISING THE SAID DERIVATIVES
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Method for preventing or inhibiting the transmission of HIV to susceptible uninfected cells by administering to the HIV, to cells infected with HIV, and/or to the uninfected cells, an effective amount of a compound of formula (I), wherein X is O or S, prior to the HIV or the cells infected with HIV, contacting the uninfected cells.
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- TRICYCLIC THIENO-AZEPINE VASOPRESSIN ANTAGONISTS
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This invention relates to new bicyclic non-peptide vasopressin antagonists which are useful in treating conditions where decreased vasopressin levels are desired, such as in congestive heart failure, in disease conditions with excess renal water reabsorption and in conditions with increased vascular resistance and coronary vasoconstriction.
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- Compounds useful for the inhibition of the replication of HIV-1 and HIV-1 mutants
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Compounds of the formula STR1 wherein X is O or S, useful for the inhibition of the replication of HIV-1 and reverse transcriptase mutants thereof, in vitro and in vivo.
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- Effects of α-tert-Butyl Group Substitution on the Reactivity and Dimerization Products of Furan-Based o-Quinodimethanes
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Flash vacuum pyrolysis (FVP) of 2-neopentyl-3-furylmethyl benzoate (8) produces 3-methylene-2-(tert-butylmethylene)-2,3-dihydrofuran (5), the major product as shown by low-temperature 1H NMR spectroscopy.Upon warming to room temperature, 5 dimerizes giving mostly two stereoisomeric dimers 11a and 11b in addition to a small amount of the dimer 12.FVP of a mixture of the two dimers 11a and 11b gives the thermodynamically more stable dimer 12.The rate constants for the dimerization of 5 in solution at temperatures from -29 to +5 deg C were determined by 1H NMR spectroscopy.The rate constants and activation parameters (ΔH(excit.) = 10.8 kcal/mol, ΔS(excit.) = -28.8 eu) are very similar to those reported for the unsubstituted furan-based o-quinodimethane.FVP of (2-methyl-3-furyl)(tert-butyl)methyl benzoate (13) and (2-neopentyl-3-furyl)(tert-butyl)methyl benzoate (18) give as the major product, 2-methylene-3-(tert-butylmethylene)-2,3-dihydrofuran (6) and 2,3-bis(tert-butylmethylene)-2,3-dihydrofuran (7), respectively.Compunds 6 and 7, in contrast to 5, are stable at room temperature apparently because for each of these compounds a bulky tert-butyl group is on the more reactive methylene, the 3-methylene.These results offer further support for the mechanism for the dimerization of furan-based o-quinodimethanes which proceeds in two steps via a transient diradical intemediate.
- Trahanovsky, Walter S.,Huang, Yih-chuan Jason,Leung, Man-kit
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p. 2594 - 2598
(2007/10/02)
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- 131. Synthesis of 2-Cycloalkenones (Parts of 1,4-Diacyl-1,3-butadiene Systems) and of a Heterocyclic Analogue by Metal-Catalyzed Decomposition of 2-Diazoacylfurans
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Furans with side-chains at C(2) of various lengths terminating in diazomethyl keto groups are shown to undergo Rh2(OAc)4-catalyzed furan unravelling with the production of 2-cyclopentenone, 2-cyclohexenone, and 2-cycloheptenone to each of whose olefinic C(β) is attached an acrylaldehyde unit.Interposition of a cyclohexane or a methylaminomethylene moiety between the furan and diazoketo functions leads to the formation of a hydroindenone and pyrrolone, respectively.Replacement of the diazomethylketo terminus by an α-diazoethylketo system or a α-diazo-β-keto-ester function produces 2-substituted 2-cycloalkenones.A furan with a C4, diazomethylketo-terminating side-chain at C(3) is described to be transformed into a 4-formylmethylidene-2-cyclohexenone.
- Wenkert, Ernest,Guo, Ming,Pizzo, Ferdinando,Ramachandran, Kishore
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p. 1429 - 1438
(2007/10/02)
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