Abstract：
:A series of substituted (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids was prepared and evaluated in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. Alkoxy, alkylthio, and isopropyl substituents at the 6- or 8-positions provided highly potent compounds. Conversion to the Z isomer, reduction of the side chain double bond, or reduction of the quinazoline ring resulted in substantial loss of activity. Among the analogues that exhibited oral activity in the PCA test, (E)-3-[6-(methylthio)-4-oxo-4H-quinazolin-3-yl]-2-propenoic acid (5i) was the most potent.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
LeMahieu RA,Carson M,Nason WC,Parrish DR,Welton AF,Baruth HW,Yaremko Bdoi
10.1021/jm00357a018subject
Has Abstractpub_date
1983-03-01 00:00:00pages
420-5issue
3eissn
0022-2623issn
1520-4804journal_volume
26pub_type
杂志文章abstract：:A novel series of 3-heteroaryl-5,6-bis(aryl)-1-methyl-2-pyridones were developed with high affinity for the benzodiazepine (BZ) binding site of human gamma-aminobutyric acid (GABA(A)) receptor ion channels, low binding selectivity for alpha 2- and/or alpha 3- over alpha 1-containing GABA(A) receptor subtypes and high ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0110789
更新日期：2002-04-25 00:00:00
abstract：:A series of 2,2'-disubstituted 5,5'-dibenzimidazolyl ketones and related compounds have been synthesized of which 2,2'-bis(carbomethoxyamino)-5,5'-dibenzimidazolyl ketone exhibited a broad spectrum of anthelmintic activity in experimental animals. At doses of 10-50 mg/kg given intraperitoneally, 5 killed 100% of the a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00157a032
更新日期：1986-07-01 00:00:00
abstract：:The crystal and molecular structure of metyrapone, a powerful inhibitor of certain cytochromes P-450, is described. Cytochrome P-450 enzymes are involved in metabolic processes, including those activating insecticides, drugs, and carcinogens. Metyrapone inhibits both the adrenal cytochrome P-450 catalyzing 11-beta-hyd...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00363a008
更新日期：1983-09-01 00:00:00
abstract：:The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Rep...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00127a041
更新日期：1989-07-01 00:00:00
abstract：:(+)-Deoxoartelinic acid (13), a new hydrolytically stable, water-soluble, and potent non-acetal-type antimalarial drug candidate, was successfully prepared from artemisinic acid by using sulfur ylide and photooxygenative cyclization in seven steps. This compound showed superior in vitro antimalarial activity against t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020244p
更新日期：2002-10-24 00:00:00
abstract：:The cardiac activity of a series of analogues of the positive inotropic bipyridines amrinone (5-amino-[3,4'-bipyridin]-6(1H)-one) and milrinone (2-methyl-5-cyano-[3,4'-bipyridin]-6(1H)-one) was evaluated in vitro in a rabbit myocardial membrane Mg(2+)-dependent, Ca(2+)-stimulable adenosine triphosphatase (Ca(2+)-ATPas...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00011a018
更新日期：1995-05-26 00:00:00
abstract：:This report describes the syntheses and structure-activity relationships of 8-(4-methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF(1)) receptor antagonists. CRF(1) receptor antagonists may be potential anxiolytic or antidepressant drugs. This research culminated in the discove...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9000242
更新日期：2009-05-14 00:00:00
abstract：:Angiogenesis is a requirement for the sustained growth and proliferation of solid tumors, and the development of new compounds that induce a sustained inhibition of the proangiogenic signaling generated by tumor hypoxia still remains as an important unmet need. In this work, we describe a new antiangiogenic compound (...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5019252
更新日期：2015-05-14 00:00:00
abstract：:Novel classes of antimalarial drugs are needed due to emerging drug resistance. Azithromycin, the first macrolide investigated for malaria treatment and prophylaxis, failed as a single agent and thus novel analogues were envisaged as the next generation with improved activity. We synthesized 42 new 9a-N substituted 15...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201615t
更新日期：2012-02-09 00:00:00
abstract：:Twenty-nine novel 3'-substituted derivatives of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3) have been synthesized by using established methods and by a new route involving manipulation of a 3'-formyl intermediate. In vitro hormone receptor binding (to intact nuclei) and in vivo thyromimetic activity (induction...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00396a008
更新日期：1988-01-01 00:00:00
abstract：:With the aim of obtaining new antitumoral agents, a series of 5,8-quinazolinediones was prepared. 5-Amino-6-methoxyquinazoline was oxidized by Fremy's salt to give 6-methoxy-5,8-quinazolinedione. Nucleophilic substitution reaction at C6, electrophilic substitution at C7, and synthesis of 7-amino-6-methoxy-5,8-quinazol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00366a011
更新日期：1983-12-01 00:00:00
abstract：:Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct se...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00078
更新日期：2016-05-12 00:00:00
abstract：:1-beta-D-Arabinofuranosylthymine (aThy; ara-T) is a potent selective anti herpes simplex virus drug. Its anhydro analogue, 2,2'-anhydro-aThy, was shown to be 9-fold less active and at least 3-fold less toxic than aThy. This compound was relatively stable at physiological pH and in strong acid but was rapidly hydrolyze...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00354a025
更新日期：1982-12-01 00:00:00
abstract：:A facile procedure is described for the conversion of morphine, via the diphosphate ester derivative 1 followed by catalytic reduction and treatment with Li/NH3, to 3-deoxy-7,8-dihydromorphine (3). Oxidation with benzophenone tert-butoxide converted 3 to the ketone 4, which on treatment with Zn/NH4Cl formed (-)-4-hydr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00144a013
更新日期：1981-12-01 00:00:00
abstract：:The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010988n
更新日期：2002-02-28 00:00:00
abstract：:The proposed sst(1) pharmacophore (J. Med. Chem. 2005, 48, 523-533) derived from the NMR structures of a family of mono- and dicyclic undecamers was used to design octa-, hepta-, and hexamers with high affinity and selectivity for the somatostatin sst(1) receptor. These compounds were tested for their in vitro binding...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801314f
更新日期：2009-05-14 00:00:00
abstract：:A series of novel chiral 7-(1-, 3-, 4-, and 6-methyl-[(1R,4R)-2,5- diazabicyclo[2.2.1]heptan-2-yl]-substituted naphthyridines has been prepared with the aim of obtaining good in vitro and in vivo antibacterial agents with a decrease of the pseudoallergic type reaction when compared to that observed with 7[(1R,4R)-2,5-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00093a024
更新日期：1992-07-24 00:00:00
abstract：:This article highlights our work toward the identification of a potent, selective, and efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational design, guided by X-ray analysis of several inhibitors bound to human chitotriosidase (hCHIT1), led to the identification of compound 7f as a highly potent AMCase i...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01051
更新日期：2018-02-08 00:00:00
abstract：:Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensi...
journal_title：Journal of medicinal chemistry
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更新日期：1998-10-22 00:00:00
abstract：:A series of 3',5'-diesters of a 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine salt bearing functional substituents on the ester side chains (4--16) have been synthesized. The synthesis of these diesters involved the reaction between cytidine and the corresponding acid anhydride or acid chloride in the presence of b...
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pub_type： 杂志文章
doi：10.1021/jm00192a007
更新日期：1979-06-01 00:00:00
abstract：:High throughput screening and subsequent optimization led to the discovery of novel quaternary ammonium salts as highly potent muscarinic acetylcholine receptor antagonists with excellent selectivity. Compounds 8a, 13a, and 13b showed excellent inhibitory activity and long duration of action in bronchoconstriction in ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800634k
更新日期：2008-08-28 00:00:00
abstract：:3,4-Dihydro-2(1H)-quinolones, evolved from 2-carboxy-1,2,3,4,- tetrahydroquinolines and 3-carboxy-4-hydroxy-2(1H)-quinolones, have been synthesized and evaluated in vitro for antagonist activity at the glycine site on the NMDA receptor and for AMPA [(RS)-alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid] antag...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00074a021
更新日期：1993-10-29 00:00:00
abstract：:Since the identification of the dopamine D(4) receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D(4) ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthe...
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更新日期：2004-06-03 00:00:00
abstract：:Opical antipodes of the axial phenyl analgetic, alpha-promedol hydrochloride (3), were prepared and the absolute stereochemistry wasd determined by relating one of the enantiomers to its gamme diastereomer having the 2S, 4S,5R configuration. The analegetic potency of (+)-(2R,4S,5S)-3 is 20 times that of morphine, whil...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00231a014
更新日期：1976-09-01 00:00:00
abstract：:A series of potent nonpeptide inhibitors of the HIV protease have been identified. Using the structure of compound 3 bound to the HIV protease, bis tertiary amide inhibitor 9 was designed and prepared. Compound 9 was found to be about 17 times more potent than 3, and the structure of the protein-ligand complex of 9 re...
journal_title：Journal of medicinal chemistry
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更新日期：1996-07-05 00:00:00
abstract：:Indolic N-benzylation of naltrindole reportedly extends the duration of delta-opioid receptor (DOR) antagonism. Similar modification of the kappa-opioid receptor (KOR) antagonist norBNI (1a) and its 17,17'-diNMe analogue (1d), a low potency mu-opioid receptor (MOR) partial agonist, was found to affect predominantly th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049172n
更新日期：2005-03-10 00:00:00
abstract：:Recently, FXIIa was highlighted as an original attractive target for the development of new anticoagulant drugs with low rates of therapy-related hemorrhages. In this work, we describe the development of a new series of 3-carboxamide-coumarins that are the first potent and selective nonpeptidic inhibitors of FXIIa. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2008-06-12 00:00:00
abstract：:A series of 1-imidazolyl(alkyl)-substituted quinoline, isoquinoline, naphthalene, benzo[b]furan, and benzo[b]thiophene derivatives was synthesized as dual inhibitors of thromboxane A(2) synthase (P450 TxA(2)) and aromatase (P450 arom). Dual inhibition of these enzymes could be a novel strategy for the treatment of mam...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2000-05-04 00:00:00
abstract：:Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 a...
journal_title：Journal of medicinal chemistry
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更新日期：2005-04-07 00:00:00
abstract：:A series of betulinic acid (BA) derivatives were designed and synthesized by introducing various fused heterocyclic rings at C-2 and C-3 positions. Their inhibitory effects of RANKL-induced osteoclastogenesis were evaluated by using a cell-based tartrate-resistant acid phosphatase (TRAP) activity assay. To our delight...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201540h
更新日期：2012-04-12 00:00:00
