Abstract：
:The solid-phase reductive alkylation of the Lys side chain in positions 6 (D) and 8 (L) and position 8 alone of the LH-RH antagonist [N-Ac-D-Nal,D-Ph2,3,D-Arg6,Phe7,D-Ala10]LH-RH was investigated in an attempt to reduce the histamine-releasing activity inherent to most potent antagonists while retaining high antiovulatory activity. The protected parent analogues were prepared by conventional solid-phase peptide synthesis. After selective removal of the Lys Fmoc side chain protection, the resin-bound peptides were readily and conveniently alkylated at the epsilon amino groups with various aldehydes and ketones in the presence of NaBH3CN. The analogues were then cleaved from the resin with simultaneous deprotection by anhydrous hydrogen fluoride and purified to homogeneity in two stages: gel permeation followed by preparative reversed-phase liquid chromatography. The analogues were assayed in standard rat antiovulatory and in vitro histamine-release assays.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Hocart SJ,Nekola MV,Coy DHdoi
10.1021/jm00393a038subject
Has Abstractpub_date
1987-10-01 00:00:00pages
1910-4issue
10eissn
0022-2623issn
1520-4804journal_volume
30pub_type
杂志文章abstract：:Two separate libraries, prepared via parallel synthesis, were employed to identify low-molecular-weight SH2-targeted ligands for the Lck tyrosine protein kinase. These libraries were constructed to furnish non-amino acid analogues of the (1) Glu-Glu and (2) Ile residues of the Lck SH2 domain peptide ligand Ac-pTyr-Glu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990462r
更新日期：2000-03-23 00:00:00
abstract：:A series of structurally related mono- and bis-1,3-disubstituted 2-[(hydroxyimino)methyl]imidazolium halides were evaluated in vitro for their ability to reactivate electric eel, bovine, and human erythrocyte (RBC) acetylcholinesterases (AChE) inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00122a034
更新日期：1989-02-01 00:00:00
abstract：:Two 12-amino-6,7,8,11-tetrahydro-7,11-methanocycloocta[b]quinoline derivatives [9-Me(Et)] (syn-huprines) have been obtained by condensation of known 7-alkylbicyclo[3.3.1]non-6-en-3-ones with 2-(trifluoromethyl)aniline, followed by basic cyclization of the resulting imine, and chromatographic separation of the regioiso...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010949b
更新日期：2001-12-20 00:00:00
abstract：:Inhibitor of apoptosis proteins (IAPs) are promising anticancer targets, given their roles in the evasion of apoptosis. Several peptidomimetic IAP antagonists, with inherent selectivity for cellular IAP (cIAP) over X-linked IAP (XIAP), have been tested in the clinic. A fragment screening approach followed by structure...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00900
更新日期：2018-08-23 00:00:00
abstract：:The effect of incorporation of an eleostearoyl group into molecules of aralkylhydrazines on their monoamine oxidase inhibitory potency was investigated in vitro and in vivo. The results showed that on a molar basis the hydrazides possessed an in vitro potency lower than and an in vivo potency and acute toxicity compar...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00235a004
更新日期：1975-01-01 00:00:00
abstract：:Reformatski condensation of benzyl 2-bromopropionate with 4-carbomethoxybenzaldehyde, followed by dehydration afforded benzyl 2-methyl-p-carbomethoxycinnamate (4a). Hydrogenation over a Pd catalyst gave the hydrocinnamic acid 5a. Conversion to the chloromethyl (6a) and azidomethyl ketone (7a) was followed by hydrogena...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a035
更新日期：1990-01-01 00:00:00
abstract：:An analogue of a tripeptide inhibitor of angiotensin converting enzyme, Bz-Phe-Gly-Pro, has been synthesized in which the amide bond connecting phenylalanine and glycine has been replaced by a ketomethylene group. This nonpeptide analogue, 20, shows more potent converting enzyme inhibiting activity, I50 = 0.07 microM,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00186a020
更新日期：1980-12-01 00:00:00
abstract：:A series of 4-methyl-3-(arylthio)furoxans were synthesized by oxidation of 1-(arylthio)-2-methylglyoxymes with dinitrogen tetroxide. Reduction with trimethyl phosphite of the furoxan derivatives afforded the corresponding furazans, while oxidation with an equimolar amount of 30% hydrogen peroxide in acetic acid or wit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00095a028
更新日期：1992-08-21 00:00:00
abstract：:Various semicarbazones derived from aryl aldehydes, phenylalkyl aldehydes, and phenylalkyl ketones as well as some related compounds were evaluated for anticonvulsant activity. Most of the compounds displayed anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00068a001
更新日期：1993-08-06 00:00:00
abstract：:In the past few years the focus on central acetylcholine receptors has shifted from compounds with affinity for muscarinic acetylcholine receptors (mAChR) to compounds with affinity for nicotinic acetylcholine receptors (nAChR). The therapeutic potential includes treatment of a variety of diseases, e.g., Alzheimer's d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990973d
更新日期：2000-06-01 00:00:00
abstract：:The academic setting provides an environment that may foster success in the discovery of certain types of small molecule tools while proving less suitable in others. For example, small molecule probes for poorly understood systems, those that exploit a specific resident expertise, and those whose commercial return is ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm400132d
更新日期：2013-09-26 00:00:00
abstract：:Alpha-galactoglycosphingolipids (alpha-GalGSLs) are unique immunostimulatory glycosphingolipids from marine sponges. Analysis of the glycosphingolipid composition of the marine sponge Axinella damicornis revealed the presence of a new alpha-GalGSL, damicoside (3a), which is the first alpha-GalGSL with a glycosylated g...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050506y
更新日期：2005-11-17 00:00:00
abstract：:Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, plays a major role in T-cell signaling downstream of the T-cell receptor (TCR), and considerable efforts have been directed toward discovery of ITK-selective inhibitors as potential treatments of inflammatory disorders such as...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500550e
更新日期：2014-07-10 00:00:00
abstract：:The bioavailability of aromatic azaheterocyclic drugs can be affected by the activity of aldehyde oxidase (AO). Susceptibility to AO metabolism is difficult to predict computationally and can be complicated in vivo by differences between species. Here we report the use of bis(((difluoromethyl)sulfinyl)oxy)zinc (DFMS) ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4017976
更新日期：2014-02-27 00:00:00
abstract：:The use of deuteration in medicinal chemistry has exploded in the past years, and the FDA has recently approved the first deuterium-labeled drug. Precision deuteration goes beyond the pure and simple amelioration of the pharmacokinetic parameters of a drug and might provide an opportunity when facing problems in terms...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.8b01808
更新日期：2019-06-13 00:00:00
abstract：:The dipeptide D-alanyl-D-alanine is an essential precursor of bacterial peptidoglycan; thus, blocking its formation is a possible target for the design of novel antibacterial agents. The synthesis of this dipeptide by bacterial D-alanine:D-alanine ligase requires ATP. In analogy with glutamine synthetase, we hypothesi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00128a033
更新日期：1989-08-01 00:00:00
abstract：:The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4+ cell types from bone marrow to peripheral circulation. We have discovered a novel series of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01322
更新日期：2018-02-08 00:00:00
abstract：:A series of 9-(hydroxyalkenyl)purines (adenines and 3-deazaadenines), which are analogues of neplanocin A, were synthesized. The analogues were tested as inhibitors of bovine liver and murine L929 cell S-adenosyhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1) and as inhibitors of vaccinia virus replication in murine L929 ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00117a011
更新日期：1988-09-01 00:00:00
abstract：:The proteasome plays a crucial role in degradation of normal proteins that happen to be constitutively or inducibly unstable, and in this capacity it plays a regulatory role. Additionally, it degrades abnormal/damaged/mutant/misfolded proteins, which serves a quality-control function. Inhibitors of the proteasome have...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01379
更新日期：2017-02-23 00:00:00
abstract：:Deregulation of CK1 (casein kinase 1) activity can be involved in the development of several pathological disorders and diseases such as cancer. Therefore, research interest in identifying potent CK1-specific inhibitors is still increasing. A previously published potent and selective benzimidazole-derived CK1δ/ε-speci...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500600b
更新日期：2014-10-09 00:00:00
abstract：:The synthesis of a series of 2-chloro- or 2-fluoro-9-(2-substituted-2-deoxy-beta-D-arabinofuranosyl)adenines (4g-n) is described. New compounds were prepared from either 2-chloroadenosine or 2-fluoroadenosine by first blocking the 3'- and 5'-hydroxyls as the tetraisopropyldisiloxane derivatives. Activation of O-2' by ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00397a024
更新日期：1988-02-01 00:00:00
abstract：:Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30) behave as weak partial agonists at cholinergic receptors in tissues of limited receptor reserve. The current paper describes the synthesis and biochemical asse...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00397a039
更新日期：1988-02-01 00:00:00
abstract：:LTX 109 is a synthetic antimicrobial peptidomimetic (SAMP) currently in clinical phase II trials for topical treatment of infections of multiresistant bacterial strains. All possible eight stereoisomers of the peptidomimetic have been synthesized and tested for antimicrobial effect, hemolysis, and hydrophobicity, reve...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200450h
更新日期：2011-08-25 00:00:00
abstract：:The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating the structure-activity relationships of its analogues and in the search for more potent and ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050879z
更新日期：2006-03-23 00:00:00
abstract：:Cyclin-dependent kinase 2 (CDK2) drives the progression of cells into the S- and M-phases of the cell cycle. CDK2 activity is largely dispensable for normal development, but it is critically associated with tumor growth in multiple cancer types. Although the role of CDK2 in tumorigenesis has been controversial, emergi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.8b01469
更新日期：2019-05-09 00:00:00
abstract：:We report the esterification of the carboxyl groups of the cyclic peptide toxins nodularin-R and microcystin-LA to produce stable diacetoxymethyl and dipropionyloxymethyl ester derivatives. The derivatives had no activity but were reactivated upon esterase treatment. When injected into cells, the acyloxymethyl moietie...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900502e
更新日期：2009-09-24 00:00:00
abstract：:This is a review of the macrolide and ketolide field focusing on differentiating the pharmacodynamics and especially the toxicology of the macrolides and ketolides. We emphasize the diversity in pharmacodynamics and toxicity of the macrolides and ketolides, resulting from even small structural changes, which makes it ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01159
更新日期：2020-06-25 00:00:00
abstract：:New carboxyalkyl compounds derived from Phe-Leu and Phe-Ala were synthesized and checked as inhibitors of "enkephalinase", a metalloendopeptidase cleaving the Gly3-Phe4 bond of enkephalins from mouse striatal membranes. Differential recognition of both brain enkephalinase and angiotensin-converting enzyme (ACE) cataly...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00355a013
更新日期：1983-01-01 00:00:00
abstract：:The protein kinase MKK7 is linked to neuronal development and the onset of cancer. The field, however, lacks high-quality functional probes that would allow for the dissection of its detailed functions. Against this background, we describe an effective covalent inhibitor of MKK7 based on the pyrazolopyrimidine scaffol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00102
更新日期：2019-03-14 00:00:00
abstract：:Previous work has shown that incorporation of either 1-aminocyclohexanecarboxylic acid (Ac6c) or alpha-methyl-p-phosphonophenylalanine ((alpha-Me)Ppp) in the phosphotyrosyl (pTyr) C-proximal position (pY + 1 residue) of Grb2 SH2 domain binding peptides confers high affinity. The tetralin-based (S)-2-amino-6-phosphonot...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0492709
更新日期：2005-02-10 00:00:00
