62882-02-4Relevant articles and documents
Synthesis of Indole-Dihydroisoquinoline Sulfonyl Ureas via Three-Component Reactions
Pearson, Stuart E.,Fillery, Shaun M.,Goldberg, Kristin,Demeritt, Julie E.,Eden, Jonathan,Finlayson, Jonathan,Patel, Anil
, p. 4963 - 4981 (2018/12/13)
Isoquinolines activated with sulfamoyl chlorides were reacted with indoles in a 3-component reaction to generate a library of dihydroisoquinoline derivatives. Using a differential protecting group strategy, products could be further derivatised. Synthesis of isoquinoline starting materials using several different methods is also described.
1-Imidazolyl(alkyl)-substituted di- and tetrahydroquinolines and analogues: Syntheses and evaluation of dual inhibitors of thromboxane A2 synthase and aromatase
Jacobs, Christoph,Frotscher, Martin,Dannhardt, Gerd,Hartmann, Rolf W.
, p. 1841 - 1851 (2007/10/03)
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 A2 synthase (P450 TxA2) and aromatase (P450 arom). Dual inhibition of these enzymes could be a novel strategy for the treatment of mammary tumors and the prophylaxis of metastases. The most potent dual inhibitors, 5-(2-imidazol-1-ylethyl)-7,8-dihydroquinoline (31) (P450 TxA2:IC50 = 0.29/μM; P450 arom: IC50 = 0.50/μM) and its 5,6- saturated analogue 30 (P450 TxA2:IC50 = 0.68/μM; P450 arom: IC50 = 0.38/μM), showed a stronger inhibition of both target enzymes than the reference compounds (dazoxiben: IC50 = 1.1/μM; aminoglutethimide: IC50 = 18.5/μM). For the determination of the in vivo activity, the influence of selected compounds on serum TxB2 concentration was examined in rats. Compound 30 (8.5 mg/kg body weight) led to a reduction of the TxB2 serum level of 78%, 71%, and 51% after 3, 5, and 8 h, respectively (dazoxiben: 60%, 34%, and 36%). Selectivity was studied toward some enzymes of the steroidogenic and eicosanoid pathways. P450 17 was inhibited by selected compounds only at high concentrations. Compound 30 inhibited P450 scc by 13% (25/μM). Compound 31 did not affect cyclooxygenase and lipoxygenase.
High-temperature rearrangements of 2-acylisoxazol-5(2H)-ones and related oxazoles
Clark, Adrian D.,Ha, Uyen T.,Prager, Rolf H.,Smith, Jason A.
, p. 1029 - 1033 (2007/10/03)
2-Acyl-3-arylisoxazol-5(2H)-ones give 2-alkyl(aryl)-4-aryloxazoles in good yields at 540°C under flash vacuum pyrolysis conditions, but at higher temperatures the expected oxazoles are accompanied by increasing amounts of isomeric 2,5-disubstituted oxazoles, as well as anilides and decomposition products of the 2,4-disubstituted oxazole. The rearrangement mechanisms have been studied by the use of 13C labelled substrates and p-substituted 3-arylisoxazolones. The 2,5-disubstituted oxazoles are considered to arise from 1H-azirines, and the anilides from the nitrone ketene isomer of the acylisoxazolone.
Intermediates for making N-aryl and N-heteroarylamide and urea derivatives as inhibitors of acyl coenzyme A: cholesterol acyl transferase (ACAT)
-
, (2008/06/13)
Compounds of the formula STR1 wherein R21 and R22 are as defined in the specification which are intermediates useful in the preparation of compounds of the formula STR2 and the pharmaceutically acceptable salts thereof, wherein Q and R1 are as defined in the specification. The compounds of formula I are inhibitors of acyl coenzyme A: cholesterol acyltransferase (ACAT) and are useful as hypolipidemic and antiatherosclerosis agents.
New N-aryl and N-heteroarylamide and urea derivatives as inhibitors of acyl coenzyme A: cholesterol acyl transferase
-
, (2008/06/13)
Compounds of the formula the pharmaceutically acceptable salts thereof, wherein Q and R1 are as defined below, and novel carboxylic acid and acid halide intermediates used in the synthesis of such compounds. The compounds of formula I are inhibitors of acyl coenzyme A: cholesterol acyltransferase (ACAT) and are useful as hypolipidemic and antiatherosclerosis agents.
Inhibitors of phenylethanolamine N-methyltransferase and epinephrine biosynthesis: I. Chloro-substituted 1,2,3,4-tetrahydroisoquinolines
Bondinell,Chapin,Girard,Kaiser,Krog,Pavloff,Schwartz,Silvestri,Vaidya,Lam,Wellman,Pendleton
, p. 506 - 511 (2007/10/02)
In a search for inhibitors of epinephrine biosynthesis as potential therapeutic agents, a series of 13 ring-chlorinated 1,2,3,4-tetrahydroisoquinolines was prepared. These compounds were tested initially for their ability to inhibit rabbit adrenal phenylethanolamine N-methyltransferase (PNMT) in vitro. Enzyme-inhibitor dissociation constants, determined for the six most potent members of the series, indicated the following order of decreasing potency: 7,8-Cl2>6,7,8-Cl3>7-Cl~8-Cl>5,6,7,8-Cl4>5,7,8-Cl3. These compounds were subsequently examined for PNMT-inhibiting activity in intact rats and mice. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline (SK&F 64139) was the most potent member of the series both in vitro and in vivo and is currently undergoing clinical investigation.
