Abstract：
:The title compound (4A) was synthesized and tested as a mechanism-based inactivator of the sterol methyl transferase (SMT) enzyme from Prototheca wickerhamii. Using cycloartenol as substrate, 4A was found to exhibit time-dependent inactivation kinetics, generating a Ki value of 30 microM and Kinact value of 0.30 min-1.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Nes WD,He L,Mangla ATdoi
10.1016/s0960-894x(98)00651-9subject
Has Abstractpub_date
1998-12-15 00:00:00pages
3449-52issue
24eissn
0960-894Xissn
1464-3405pii
S0960894X98006519journal_volume
8pub_type
杂志文章abstract：:The structure-activity relationships of new Aurora A/B kinase inhibitors derived from the previously identified kinase inhibitor 12 are described. Introduction of acetic acid amides onto the pyrazole of compound 12 was postulated to influence Aurora A/B selectivity and improve the profile against off-target kinases. T...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2012.03.051
更新日期：2012-05-15 00:00:00
abstract：:We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family. Computational and crystal...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2013.03.015
更新日期：2013-05-01 00:00:00
abstract：:To develop potent chemotherapeutic agents for treating colorectal cancers, polymethoxylated 3-naphthyl-5-phenylpyrazoline-carbothioamide derivatives were designed. Twenty-two novel derivatives were synthesized and their cytotoxicities were measured using a clonogenic long-term survival assay. Of these derivatives, 3-(...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2016.07.037
更新日期：2016-09-01 00:00:00
abstract：:A new series of 5-[(3'-chloro-4',4'-disubstituted-2-oxoazetidinyl)(N-nitro)amino]-6-hydroxy-3-alkyl/aryl[1,3]azaphospholo[1,5-a]pyridin-1-yl-phosphorus dichlorides has been synthesized and subjected to acute antibacterial and antifungal screening studies. All the derivatives belonging to this series delineated remarka...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.12.050
更新日期：2005-02-15 00:00:00
abstract：:A series of thirty-seven 1,3,5-triazine analogues have been synthesized, characterized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines such as HeLa, HepG2, A549 and MCF-7. Most of the 1,3,5-triazine analogues exhibited promising antiproliferative activity ag...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2017.06.060
更新日期：2017-08-15 00:00:00
abstract：:Although PK11195 binds to the peripheral benzodiazepine receptor with nanomolar affinity, significant data exist which suggest that it has another cellular target distinct from the PBR. Here we demonstrate that PK11195 inhibits F(1)F(0)-ATPase activity in an OSCP-dependent manner, similar to the pro-apoptotic benzodia...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2006.12.102
更新日期：2007-03-15 00:00:00
abstract：:From our modulator library an interesting inhibitor of breast cancer resistance protein (BCRP) was identified. Due to its high inhibitory potency, this compound may serve as a promising novel lead for the design of new and potent modulators. This adds a new structural class to the few known highly active BCRP inhibito...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2009.11.004
更新日期：2010-01-01 00:00:00
abstract：:A series of prodrugs of stavudine were synthesized in an effort to enhance spectrum of chemotherapeutic properties for the effective treatment of HIV/AIDS. The 5'-OH function of stavudine was esterified with ciprofloxacin, norfloxacin, isoniazide, pyrazinamide, piperazine and dimethylamine acetic acid. The anti-HIV-1 ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.01.007
更新日期：2004-03-08 00:00:00
abstract：:Following the promising activity of Q2FA15 on axonal growth, two new series of N/O-substituted QFAs were synthesized, based on a SN2-type reaction. O-alkylated QFA bearing 14 carbon atoms on the side chain (n=14) shows a very potent activity on axonal growth though lowered when compared to Q2FA15. While O-alkylation a...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2006.05.027
更新日期：2006-08-01 00:00:00
abstract：:Lead optimisation of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine class led to the identification of two clinical leads [RO4882224 (11) and RO4938581 (44)] functioning as novel potent and selective GABAA alpha5 inverse agonists. The unique pharmacological profiles and optimal pharmacokinetic profiles r...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2009.08.053
更新日期：2009-10-15 00:00:00
abstract：:A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1-36) were synthesized via Pictet-Spengler cyclization. All the synthesized compounds were assayed for activities against HIV-1(IIIB) in C8166 cell cultures by MTT method for the first time. The results of the anti-HIV screening reve...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2008.02.040
更新日期：2008-04-01 00:00:00
abstract：:The stereochemistry of the tubulin inhibitors taltobulin HTI-286 (2) and HTI-042 (3) was determined by utilizing the DPFGSE 1D NOE experiment. Single crystal X-ray diffraction analysis further confirmed the absolute configuration of these two compounds, which carry the (S,S,S)-configuration necessary for biological ac...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2010.01.047
更新日期：2010-03-01 00:00:00
abstract：:Introduction of 3-substituted azetidinyl substituents onto the 4,6-diaminopyrimidine scaffold allowed the improvement of PDE4 inhibiting activities. Preliminary in vivo activity in pulmonary inflammation models is reported. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2007.03.047
更新日期：2007-06-01 00:00:00
abstract：:The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time de...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2011.01.131
更新日期：2011-03-15 00:00:00
abstract：:The synthesis of racemic tetrahydrocurcumin- (THC-), tetrahydrodemethoxycurcumin- (THDC-) and tetrahydrobisdemethoxycurcumin- (THBDC-) dihydropyrimidinone (DHPM) analogues was achieved by utilizing the multi-component Biginelli reaction in the presence of copper sulphate as a catalyst. The evaluation of acetylcholines...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2013.03.069
更新日期：2013-05-15 00:00:00
abstract：:The discovery, synthesis, and SAR of chromanes as ER alpha subtype selective ligands are described. X-ray studies revealed that the origin of the ER alpha-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2005.01.046
更新日期：2005-03-15 00:00:00
abstract：:The synthesis and SAR of a novel series of non-nucleoside pyridopyrimidine inhibitors of the enzyme adenosine kinase (AK) are described. It was found that pyridopyrimidines with a broad range of medium and large non-polar substituents at the 5-position potently inhibited AK activity. A narrower range of analogues was ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(00)00602-8
更新日期：2001-01-08 00:00:00
abstract：:Based on previous SAR studies on N-benzylindole and barbituric acid hybrid molecules, we have synthesized a series of aromatic substituted 5-((1-benzyl-1H-indol-3-yl)methylene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione analogs (3a-i) and evaluated them for their in vitro growth inhibition and cytotoxicity against ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2013.12.013
更新日期：2014-01-15 00:00:00
abstract：:Extensive SAR studies and optimization of ADME properties of benzimidazol-2-one derivatives led to the identification of BMS-433771 (3) as an orally active RSV fusion inhibitor. In order to extend the structure-activity relationships for this compound series, substitution of the benzimidazole ring was examined with a ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2007.05.102
更新日期：2007-08-15 00:00:00
abstract：:A series of cis-2,6-dialkyl-4-chloro-tetrahydropyrans were prepared by means of an iron(III)-catalyzed process. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, SW1573, and WiDr. The results show that the presence of bulky substituents favors the Prins cyclization lead...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2006.03.064
更新日期：2006-06-15 00:00:00
abstract：:The design, synthesis, and enzyme kinetics evaluation of a transition-state inhibitor of glyoxalase-I is described. The union of the hydroxamic acid zinc-chelator with a urea isostere for the glu-cys amide bond led to a glutathione analog which retained inhibitory potency toward glyoxalase-I while possessing resistanc...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2006.08.121
更新日期：2006-12-01 00:00:00
abstract：:Novel prostaglandin E2 receptor 4 (EP4) agonists featuring a pyridone core and an allylic alcohol ω-chain were discovered. These agonists were shown to be selective over EP1, EP2 and EP3. Analogs harboring a 4-carboxylic acid phenethyl α-chain displayed improved potency over those containing an n-heptanoic acid chain....
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2020.127104
更新日期：2020-05-15 00:00:00
abstract：:Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole carboxylates 1a-1p and corresponding acid derivatives 2a-2p. All 32 novel compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for in vitro ant...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2015.02.004
更新日期：2015-03-15 00:00:00
abstract：:The synthesis of the beta-peptide 1 by the postsynthetic modification of the corresponding amino-containing peptide 3 is described. The potential of 1 to act as a template for the ligation of complementary negatively-charged peptides is discussed. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(01)00027-0
更新日期：2001-03-12 00:00:00
abstract：:A series of novel arylsulfonylpropargylglycinamide derivatives was investigated as thrombin inhibitors in which the SAR was focused on substituents at the acetylenic terminus. Several compounds in this series were identified as potent thrombin inhibitors (Ki up to 5 nM) that are highly selective over trypsin and other...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(99)00125-0
更新日期：1999-04-05 00:00:00
abstract：:To identify small molecule inhibitors of TNF-α, bioassay- and LC-MS-guided chemical investigation on EtOAc extract of Pseudomonas aeruginosa ABS-36 culture broth (EEPA) was performed, which yielded four proline-based cyclic dipeptides, cyclo(Gly-l-Pro) (1), cyclo(l-Pro-l-Phe) (2), cyclo(trans-4-hydroxy-l-Pro-l-Phe) (3...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2015.10.075
更新日期：2015-12-15 00:00:00
abstract：:Isoxazoles are frequently used amide isosteres, as shown in the context of discovery of CRTh2 antagonists from amide 1 to isoxazole 2. However, persistent agonism and poor solubility in isoxazole series presented challenges to its further development. Based on the concept of quality by design (QbD), 5,5-disubstituted ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2014.01.043
更新日期：2014-03-15 00:00:00
abstract：:We report the use of fragment screening and fragment based drug design to develop a PI3γ kinase fragment hit into a lead. Initial fragment hits were discovered by high concentration biochemical screening, followed by a round of virtual screening to identify additional ligand efficient fragments. These were developed i...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2011.07.117
更新日期：2011-11-01 00:00:00
abstract：:A series of 2,6-dimethoxylpyridinyl phosphine oxides have been synthesized and examined for their antitumor activity. 2,6-Dimethoxy-3-phenyl-4-diphenylphosphinoylpyridine 2 has been employed as the lead compound for this study. We found out that the presence of phosphine oxide on the 2,6-dimethoxylpyridine ring is imp...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2009.02.091
更新日期：2009-04-15 00:00:00
abstract：:We report the first biological evaluation the 1,2,3-thiaselenazole class of compound and utilising a concise synthetic approach of sulfur extrusion, selenium insertion of the 1,2,3-dithiazoles. We created a small diverse library of compounds to contrast the two ring systems. This approach has highlighted new structure...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2019.05.016
更新日期：2019-07-15 00:00:00
