Novel [D-Arg2]dermorphin(1-4) analogs with mu-opioid receptor antagonist activity

Ten Tyr-D-Arg-Phe-betaAla-NH(2) (YRFB) analogs in which specific amino acid side chains are shifted to the N(alpha)-position were synthesized, and the binding to these analogs to the mu receptor and their in vitro biological properties were evaluated. Some analogs in which a N,N-bis(p-hydroxybenzyl)-Gly residue was substituted for Tyr(1) exhibited mu receptor antagonist activities (pA(2)) between 5.3 and 6.1. Of these analogs, [N,N-bis(p-hydroxybenzyl)-Gly(1)]YRFB was found to be the most potent specific antagonist for the mu-opioid receptor.     

Synthesis and analgesic activity of novel heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives

In order to develop analgesic compounds possessing a sulfur atom in the alicyclic ring, novel cis-fused heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives (II) were synthesized via a unique cyclization reaction starting from 4-(4-methoxyphenylthio)-2-butanone (1) or 6-methoxy-3,4-dihydro-2H-1-benzothiopyran-4-one (7). The analgesic effects of benzothiopyranopyrroles (16, 18) were measured by means of the writhing test. The phenolic derivative 18 completely inhibited the appearance of writhing at the dose of 50 mg/kg, but the methoxy derivative 16 had no analgesic effect.     

苷类化合物研究 IV: 熊果苷类似物的合成

本文报道以1-溴-2,3,4,6-四-O-乙酰基-a-D-吡喃糖与苯二酚在氢氧化钠的丙酮-水溶液中反应, 生成熊果苷类似物. 由^1HNMR测定了糖苷的端基异构体.     

Synthesis and reactivity of oxopyrrolidinothieno[2]azepinones: [3]Benzazepine antidepressant analogs

A synthesis of oxopyrrolidino[2]azepinones annelated to a thiophene ring 3a,b,c is described starting from succinimide and halogenomethylthiophenes 6a,b,c . Stereoselective reduction, Schmidt reaction and the Beckmann rearrangement of the oximes of the ketones 3a,b,c are studied.     

Synthesis of pyrazolo[4,5-d]- and pyrazolo[4,5-c][1]benzazepine derivatives. IV

Following our reports on synthetic tricyclic analogues of antitumor anthramycin the synthesis of some isomers pyrazolo[4,5-d]- and pyrazolo[4,5-c][1]benzazepine derivatives is reported.     

Studies on antiulcer drugs. IV. Synthesis and antiulcer activities of imidazo[1,2-a]pyridinylethylbenzothiazoles and -benzimidazoles.

A series of 6-[2-(imidazo[1,2-a]pyridin-2-yl)ethyl]benzothiazoles (II) and benzimidazole analogues (III) was synthesized and tested for histamine H2-receptor antagonist, gastric antisecretory and anti-stress ulcer activity. A benzimidazole derivative (IIIa) exhibited strong antisecretory activity, whereas the corresponding benzothiazole derivative (IIb) lacked this potency in in vivo test. In contrast to compound IIIa, however, compound IIb demonstrated good inhibition against stress induced ulcer. The structure-activity relationships of these compounds are discussed.     

Structure-activity relationships (SAR) of [D-Arg(2)]dermorphin(1-4) analogues,N(alpha)-amidino-Tyr-D-Arg-Phe-X

In investigating the development of compounds with potent analgesic effects after oral administration, 74 C-terminal analogues (N(alpha)-amidino-Tyr-D-Arg-Phe-X), based on the structure of N(alpha)-amidino-Tyr-D-Arg-Phe-Me beta Ala-OH (ADAMB), were synthesized. Their analgesic activity was evaluated using the mouse-tail pressure test after both subcutaneous and oral administration, and the structure-activity relationships (SAR) were examined in detail. The results clearly indicated that compounds containing beta-amino acid without a side chain at the X position are preferable for expression of potent analgesic activity, and that the free carboxyl group is superior in its analgesic activity to that of the esterified or amidated carboxy group at the C-terminal. In addition, N-methylation of the amide bond at the 4th position contributed to improved analgesic activity. These results indicated that the strong and long-lasting analgesic effect of ADAMB is expressed by the synergistic effects of N(alpha)-amidination, the N-methylation of the amide bond at the 4th position and the carbon chain length (beta-Ala) of the residue at the 4th position, and that this is the most suitable structure.     

Synthesis of cis-bicyclo[4.3.0]non-2-ene derivatives. The potent homoisocarbacyclin analogs

Synthesis of homoisocarbacyclin has been achieved efficiently by a general strategy with stereo- and regiochemical control. One of homoisocarbacyclin derivatives, 3-oxa homoisocarbacyclin analog (4), was shown to be potently active in inhibiting gastric ulcer. Another analog, conjugated diene derivative (5), was found to have a biological profile similar to prostacyclin.     

Synthesis and photoconductivity study of phthalocyanine polymers. IV. [SiPcNHCH2CH2NH]n

The preparation of a novel polymer of ethylenediamine bridged polymeric silicon phthalocyanine ( I ) with quasi-one-dimensional structure is described. The product was obtained by the condensation polymerization of ethylenediamine and silicon dichloride phthalocyanine (Cl₂SiPc) monomers and was characterized by IR and UV/VIS spectroscopy and elemental analysis. The photoconductivity of the polymer I with the quasi-one-dimensional structure is much better than that of not only the corresponding Cl₂SiPc monomer, but also other phthalocyanine polymers whose molecules are not one-dimensional structures, and showing the one-dimensional effects of molecular structure of increasing photoconductivity. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 959–964, 1997