著者

Shigetoshi Oiki Masayuki Iwamoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.3, pp.303-311, 2018-03-01 (Released:2018-03-01)

参考文献数

82

被引用文献数

12

---

Fluidity and mosaicity are two critical features of biomembranes, by which membrane proteins function through chemical and physical interactions within a bilayer. To understand this complex and dynamic system, artificial lipid bilayer membranes have served as unprecedented tools for experimental examination, in which some aspects of biomembrane features have been extracted, and to which various methodologies have been applied. Among the lipid bilayers involving liposomes, planar lipid bilayers and nanodiscs, recent developments of lipid bilayer methods and the results of our channel studies are reviewed herein. Principles and techniques of bilayer formation are summarized, which have been extended to the current techniques, where a bilayer is formed from lipid-coated water-in-oil droplets (water-in-oil bilayer). In our newly developed method, termed the contact bubble bilayer (CBB) method, a water bubble is blown from a pipette into a bulk oil phase, and monolayer-lined bubbles are docked to form a bilayer through manipulation by pipette. An asymmetric bilayer can be readily formed, and changes in composition in one leaflet were possible. Taking advantage of the topological configuration of the CBB, such that the membrane’s hydrophobic interior is contiguous with the surrounding bulk organic phase, oil-dissolved substances such as cholesterol were delivered directly to the bilayer interior to perfuse around the membrane-embedded channels (membrane perfusion), and current recordings in the single-channel allowed detection of immediate changes in the channels’ response to cholesterol. Chemical and mechanical manipulation in each monolayer (monolayer technology) allows the examination of dynamic channel-membrane interplay.

著者

西村 卓三 清水 文治 岩井 一成

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.11, no.11, pp.1470-1472, 1963-11-25 (Released:2008-03-31)

被引用文献数

35 55

著者

Shu-Hua Qi Si Zhang Cheng-Hai Gao Qin-Xing Li

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.58, no.6, pp.884, 2010-06-01 (Released:2010-06-02)

被引用文献数

2 3

著者

Jun Ho Kim Jin Hyup Lee Young Jun Kim

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b15-00585, (Released:2015-11-06)

参考文献数

14

---

This article has been retracted by the Editorial Committee of The Pharmaceutical Society of Japan because it contains scientific misconduct. Although the data published in this article were generated in part by the first author, the authors violated authorship and sponsorship protocol.

著者

Kazuaki Matsumoto Akari Shigemi Kazuro Ikawa Naoko Kanazawa Yuko Fujisaki Norifumi Morikawa Yasuo Takeda

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.38, no.2, pp.235-238, 2015-02-01 (Released:2015-02-01)

参考文献数

17

被引用文献数

5 22

---

Ganciclovir is a nucleoside guanosine analogue that exhibits therapeutic activity against human cytomegalovirus infection, and is primarily excreted via glomerular filtration and active tubular secretion. The adverse effects induced by ganciclovir therapy are generally of a hematological nature and include thrombocytopenia and leukopenia. Low marrow cellularity and elevated serum creatinine have been identified as risk factors for ganciclovir-induced neutropenia. However, the risk factors for thrombocytopenia have yet to be determined. Therefore, this study investigated patients administered ganciclovir to determine the risk factors for thrombocytopenia and leukopenia. Thrombocytopenia occurred in 41 of these patients (30.6%). Multivariate logistic regression analysis identified three independent risk factors for thrombocytopenia: cancer chemotherapy (odds ratio (OR)=3.1), creatinine clearance (<20 mL/min) (OR=12.8), and the ganciclovir dose (≥12 mg/kg/d) (OR=15.1). Leukopenia occurred in 36 patients (28.6%), and white blood cell count (<6000 cells/mm3) (OR=3.7) and the ganciclovir dose (≥12 mg/kg/d) (OR=7.8) were identified as risk factors. These results demonstrated that several factors influenced the occurrence of ganciclovir-induced thrombocytopenia and leukopenia, and suggest that special attention should be paid to patients receiving cancer chemotherapy with a low creatinine clearance (<20 mL/min) and high dose (≥12 mg/kg/d) in order to avoid ganciclovir-induced thrombocytopenia.

著者

Hajime KATAYAMA Yusuke KAWADA Kimiyoshi KANEKO Takamitsu OSHIYAMA Noriyuki TAKATSU

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.47, no.1, pp.48-53, 1999-01-15 (Released:2008-03-31)

参考文献数

31

被引用文献数

9 17

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A new type of synthetic inhibitor of DNA topoisomerase I and II was examined and several of these derivatives exhibited strong dual activity against these enzymes. This series of compounds showed high cytotoxic activities against cancer cells, but only a limited number of compounds showed any noticeable activity in an in vivo test against murine P388. Non-specific toxicity was observed in the in vivo tests.

著者

Shuichi Fujimoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.10, pp.1923-1929, 2007-10-01 (Released:2007-10-01)

参考文献数

46

被引用文献数

12 22

---

TAS-103, 6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno-[2,1-c]quinolin-7-one dihydrochloride, is a dual topoisomerases I and II inhibitor. Antitumor activities of TAS-103 against fresh surgical specimens resected from 525 patients (32 types of tumors) were examined by flow cytometric (FCM) analysis of DNA integrity of tumor cells, and compared with those of five other investigational new drugs and 31 clinically available anticancer agents. Concentrations of clinically available anticancer agents were set at one-tenth of the peak plasma concentration (PPC) of the clinically recommended doses. On the other hand, since PPCs of investigational new drugs in humans were frequently unknown, these were estimated by a method that determines the theoretically achievable concentration in body fluid (TAC method). Correlations between TAC and PPC were examined for 16 clinically available anticancer agents, and it was found that TAC at 7n (the modified Fibonacci's dose-escalation scheme) of 14 drugs corresponded well with each one-tenth of PPC. By defining a 30% or more reduction in the integrated diploid peak as effective and a 60% or more reduction as definitely effective, TAS-103 at 5 μg/ml (7n) showed significantly higher effective rates and definitely effective rates than those of all other investigational new drugs, as well as almost all clinically available anticancer agents, against various malignancies, including non-small cell lung cancer, brain tumor and renal cancer. These results strongly suggest that TAS-103 will be expected to show excellent antitumor activities against a wide range of human tumors.

著者

Judith RAZAFIMBELO Genevieve BAUDOUIN Francois TILLEQUIN Pierre RENARD Stephane LEONCE Alain PIERRE Ghanem ATASSI

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.46, no.1, pp.34-41, 1998-01-15 (Released:2008-03-31)

参考文献数

33

被引用文献数

3 4

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Condensation of 5-amino, 6-amino, 7-amino and 8-amino-2, 2-dimethyl-2H-chromenes with either 6-bromo-veratraldehyde or 6-chloropiperonal afforded the corresponding Schiff bases, which were subsequently reduced to the corresponding benzylchromenylamines 30-33 and 36-39. Lithium diisopropylamide-mediated cyclization of those amines, followed by spontaneous air oxidation, afforded pyranophenanthridines 3-14. The cytotoxicity of compounds 3-14 was evaluated against L1210 and HT29 cell lines. 9, 9-Dimethyl-9H-pyrano[3, 2-b]phenanthridines appear to be the most promising compounds of the series, since both the dimethoxy derivative 11 and the methylenedioxy derivative 12 exhibit significant cytotoxic activity. Compound 12 was the most active and induced a massive accumulation of cells in G2+M phases, suggesting that the cytotoxicity is due to a perturbation of the integrity or function of DNA.

著者

Kosuke Shimizu Miki Takada Tomohiro Asai Koichi Kuromi Kazuhiko Baba Naoto Oku

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.25, no.10, pp.1385-1387, 2002 (Released:2002-10-01)

参考文献数

19

被引用文献数

6 8

---

A novel anti-tumor agent, 6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103), effectively inhibits both topoisomerase I and II activities. To enhance anti-tumor efficacy and to reduce the side effects of the agent, liposomalization of TAS-103 was performed. TAS-103 was effectively entrapped in liposomes by a remote-loading method, and was stable at 4 °C and in the presence of 50% serum. To evaluate the anti-tumor efficacy of liposomal TAS-103, the growth inhibition against Lewis lung carcinoma cells in vitro and the therapeutic efficacy against solid tumor-bearing mice in vivo were examined. Liposomal TAS-103 showed strong cytotoxic effect against Lewis lung carcinoma cells in a dose dependent manner and effectively suppressed solid tumor growth accompanying longer survival time of tumor-bearing mice in comparison with the mice treated with free TAS-103. These results suggest that liposomal TAS-103 is useful for cancer therapy.

著者

山脇 一郎 鈴木 雅博 小川 和男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.42, no.4, pp.963-971, 1994-04-15 (Released:2008-03-31)

参考文献数

23

被引用文献数

1 1

---

Piperazinealkanol ester derivatives of indomethacin were prepared and tested for inhibitory activities against 5-lipoxygenase (5-LO) and cyclooxygenase (CO). They inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) formation by the cytosol of guinea pig polymorphonuclear leukocytes and thromboxane B2 (TXB2) formation by washed rabit platelet suspension. Of the test compounds, 2-[4-(2-hydroxyethyl)-1-piperazinyl]-1-phenylethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetate dimaleate (II-8) was found to be the most active dual inhibitor of 5-LO and CO, and its inhibitory potency was higher than that of 2-[4-(3-hydroxypropyl)-1-piperazinyl]-ethyl [1-(4-chlorobenzoyl)-5-methoxy-2-methyl]-3-indolylacetate (CR-1015) (I), the lead compound.

著者

秋山 稔 大石 順一 白井 孝 明石 景泰 吉田 浩一 錦戸 条二 林 絋 白淵 穣 西村 大吉 伊藤 平隆 渋屋 千征 石田 寅夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.26, no.3, pp.981-984, 1978-03-25 (Released:2008-03-31)

被引用文献数

14 21

---

In order to obtain 1-β-D-arabinofuranosylcytosine derivatives with better antitumor effect, 12 kinds of saturated fatty acyl groups were introduced at the N4-position of 1-β-D-arabinofuranosylcytosine. The presence of a great excess of water and about two-fold equivalents of carboxylic anhydride was found to be most desirable for selective N4-acylation. This simple method of one-step N4-acylation should be generally applicable to cytosine nucleosides and a variety of carboxylic anhydrides.

著者

Jin Sun Lee Myung Sun Lee Won Keun Oh Ji Young Sul

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.32, no.8, pp.1427-1432, 2009-08-01 (Released:2009-08-01)

参考文献数

34

被引用文献数

26 53

---

Fatty acid synthase (FASN) is highly expressed in breast carcinomas to support their continuous growth and proliferation, but has low expression level in normal tissues. Considerable interest has been developed in searching for novel FASN inhibitors as a therapeutic target for breast cancer. In present study, amentoflavone was isolated from Selaginella tamariscina, a traditional oriental medicine that has been used to treat cancer for many years, and was found to significantly inhibit the in vitro enzymatic activity of FASN at concentrations above 50 μM. Amentoflavone was also found to decrease fatty acid synthesis by the reduction of [3H]acetyl-CoA incorporation into lipids in FASN-overexpressed SK-BR-3 human breast cancer cells. Furthermore, this study showed that amentoflavone, at a concentration greater than 75 μM, increased the cleavage-activity of caspase-3 and poly (ADP-ribose) polymerase (PARP), and administration of pan-caspase inhibitor Z-VAD-FMK completely rescued the SK-BR-3 cells from PARP cleavages. The sequential internucleosomal DNA fragmentation in SK-BR-3 cells was observed at a concentration of 100 μM. A decrease in breast cancer cell growth was observed in SK-BR-3 cells at 12 and 24 h post treatment with 100 μM of amentoflavone, followed by a dramatic suppression after 48 h. The inhibition of cancer-growth by amentoflavone was dose-dependent, showing a slight reduction at 50 μM and significant reduction at concentrations of 75 and 100 μM. FASN-nonexpressed NIH-3T3 normal cell growth was not decreased by amentoflavone-treatment, both in time- and dose-dependent manners. These data provide evidence that amentoflavone isolated from S. tamariscina induced breast cancer apoptosis through blockade of fatty acid synthesis.

著者

Takashi Asada Shigehisa Ishihara Takeshi Yamane Akemi Toba Akifumi Yamada Kikuo Oikawa

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Health Science (ISSN:13449702)

巻号頁・発行日

vol.48, no.6, pp.473-479, 2002 (Released:2002-12-05)

参考文献数

10

被引用文献数

76 153

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We examined the relationship between the carbonizing temperature of bamboo carbide made from Moso bamboo (Phyllostachys pubescens) and the removal effect of harmful gases and odorants, and the use of a bamboo charcoal as a countermeasure for “Sick Building Syndrome” or “Chemical Sensitivity” and the use as a deodorant. With regard to the carbonizing temperature of the bamboo charcoal, a temperature sensor was installed inside each bamboo material and the carbonizing temperature was controlled at 500, 700 and 1000°C. The removal effect was tested for formaldehyde, toluene and benzene that are known to cause “Sick Building Syndrome” or “Chemical Sensitivity” and for ammonia, indole, skatole and nonenal as odorants. The formaldehyde removal effect was only slightly different in the charcoal at all the carbonizing temperatures. The benzene, toluene, indole, skatole and nonenal removal effect were the highest for the bamboo charcoal carbonized at 1000°C and tended to increase as the carbonizing temperature of the bamboo charcoal increased. The removal effect for ammonia was the highest on the bamboo charcoal carbonized at 500°C. It is concluded that the effective carbonizing temperature is different for each chemical, and a charcoal must be specifically selected for use as an adsorbent or deodorant.

著者

Zhihua Yue Jinhai Shi Haona Li Huiyi Li

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.2, pp.158-162, 2018-02-01 (Released:2018-02-01)

参考文献数

25

被引用文献数

11

---

Nonsteroidal anti-inflammatory drugs (NSAIDs) are likely to be used concomitantly with acyclovir or valacyclovir in clinical practice, but the study on the safety of such combinations was seldom reported. The objective of the study was to investigate reports of acute kidney injury (AKI) events associated with the concomitant use of oral acyclovir or valacyclovir with an NSAID by using the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database between January 2004 and June 2012. The frequency of AKI events in patients while simultaneously taking either acyclovir or valacyclovir and an NSAID was compared using the Chi-square test. The effect of concomitant use of acyclovir or valacyclovir and individual NSAIDs on AKI was analyzed by the reporting odds ratio (ROR). The results showed that AKI was reported as the adverse event in 8.6% of the 10923 patients taking valacyclovir compared with 8.7% of the 2556 patients taking acyclovir (p=NS). However, AKI was significantly more frequently reported in patients simultaneously taking valacyclovir and an NSAID (19.4%) than in patients simultaneously taking acyclovir and an NSAID (10.5%) (p<0.01). The results also suggested that increased risk of AKI was likely associated with the concomitant use of valacyclovir and some NSAIDs such as loxoprofen, diclofenac, etodolac, ketorolac, piroxicam or lornoxicam. The case series from the AERS indicated that compared with acyclovir, valacyclovir is more likely to be affected by NSAIDs, and the concomitant use of valacyclovir with some NSAIDs might be associated with increased risk of AKI. The drug interactions with this specific combination of medications are worth exploring further.

著者

Kazuyuki Furuya Noriko Yamamoto Yuki Ohyabu Teruyuki Morikyu Hirohide Ishige Michael Albers Yasuhisa Endo

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.36, no.3, pp.442-451, 2013-03-01 (Released:2013-03-01)

参考文献数

56

被引用文献数

8 26

---

Selective androgen receptor modulators (SARMs) comprise a new class of molecules that induce anabolic effects with fewer side effects than those of other anabolic agents. We previously reported that the novel SARM S-101479 had a tissue-selective bone anabolic effect with diminished side effects in female animals. However, the mechanism of its tissue selectivity is not well known. In this report, we show that S-101479 increased alkaline phosphatase activity and androgen receptor (AR) transcriptional activity in osteoblastic cell lines in the same manner as the natural androgen ligand dihydrotestosterone (DHT); conversely, stimulation of AR dimerization was very low compared with that of DHT (34.4%). S-101479 increased bone mineral content in ovariectomized rats without promoting endometrial proliferation. Yeast two-hybrid interaction assays revealed that DHT promoted recruitment of numerous cofactors to AR such as TIF2, SRC1, β-catenin, NCoA3, gelsolin and PROX1 in a dose-dependent manner. SARMs induced recruitment of fewer cofactors than DHT; in particular, S-101479 failed to induce recruitment of canonical p160 coactivators such as SRC1, TIF2 and notably NCoA3 but only stimulated binding of AR to gelsolin and PROX1. The results suggest that a full capability of the AR to dimerize and to effectively and unselectively recruit all canonical cofactors is not a prerequisite for transcriptional activity in osteoblastic cells and resulting anabolic effects in bone tissues. Instead, few relevant cofactors might be sufficient to promote AR activity in these tissues.

著者

赤羽 健司 永野 泰夫 梅山 秀明

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.37, no.1, pp.86-92, 1989-01-25 (Released:2008-03-31)

参考文献数

26

被引用文献数

4 8

---

Two empirical indices accounting for the hydrophobic interaction are described. The first index is a "hydrophobic field-effect (Hf) index, "which indicates the hydrophobic nature of the binding site of a host molecule such as an enzyme, and the second index is a "hydrophobic correlation (Hc) index", which indicates the hydrophobic correspondency between a host molecule and its guest molecule such as a ligand. Furthermore, a method to calculate the surface area of a molecule is described, in which the molecular surface is treated as a set of area-preserving spherical triangles. The hydrophobic effects on the interaction between papain and its inhibitor benzyloxycarbonyl-L-phenylalanyl-L-alanyl-methylene (Z-Phe-Ala-CH2-), which is covalently bound to catalytic Cys Sγ of the enzyme, were investigated by using these indices. It is quantitatively shown that the binding sites interacting with the benzene rings of P2 Phe and P3 Z are more hydrophobic, while the site of the carbonyl group of P1 Ala is more hydrophilic. The substrate specificity of papain can be explained in part by these indices. Both the Hc and Hf indices are visualized by using computer graphics. These indices would be useful as quantitative structure-activity relationship (QSAR) parameters.

著者

Yasuki YAMADA Koji ANDO Yukishige IKEMOTO Hiroki TADA Eiji SHIRAKAWA Eiji INAGAKI Saizo SHIBATA Ikuro NAKAMURA Yoshiharu HAYASHI Kiyoteru IKEGAMI Itsuo UCHIDA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.45, no.10, pp.1631-1641, 1997-10-15 (Released:2008-03-31)

参考文献数

32

被引用文献数

4 4

---

A series of renin inhibitors containing the (2S, 3S, 5S)-2-amino-1-cyclohexyl-6-methyl-3, 5-heptanediol (2-amino-3, 5-anti-diol) fragment as a novel transition-state mimic was synthesized, and their biological activities were evaluated. All of the synthesized compounds containing the 2-amino-3, 5-anti-diol fragment at the P1-P1' position showed high in vitro renin-inhibitory activity with IC50 values in the 10-8-10-10M range, and most of them caused a reduction of blood pressure when administered orally to salt-depleted, conscious marmosets. The inhibitor (29) with the 4-hydroxypiperidine residue at the P4 position showed the highest activity in terms of both potency and duration of the blood pressure-lowering effect.

著者

赤羽 健司 上條 哲聖 飯塚 欣二 田口 武夫 小林 義郎 木曽 良明 梅山 秀明

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.36, no.9, pp.3447-3452, 1988-09-25 (Released:2008-03-31)

参考文献数

31

被引用文献数

3 4

---

The structure-activity relationship of acyl-His-trifluorinated leucinol derivatives as inhibitors of human renal renin is discussed based upon the tertiary structure of human renin, which was deduced from the crystal structure of penicillopepsin by assuming structural similarity. The structural requirements for the inhibitors and possible interactions at the renin binding site are discussed.

著者

飯塚 欣二 上條 哲聖 原田 弘 赤羽 健司 久保田 哲弘 島岡 巌 梅山 秀明 木曽 良明

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.36, no.6, pp.2278-2281, 1988-06-25 (Released:2008-03-31)

参考文献数

11

被引用文献数

4 4

---

New human renin inhibitors were designed from transition-state analogues of angiotensinogen, synthesized and evaluated. The peptide derovative, which contained 1-naphthylmethylsuccinylamide residue (P3) with a retro-inverso amide bond and a norstatine isoamylamide residue (P1-P1'), was stable to proteases and had potent human renin inhibitory activity. This compact inhibitor exhibited hypotension when administered orally to a monkey.

著者

飯塚 欣二 上條 哲聖 原田 弘 赤羽 健司 久保田 哲弘 江藤 裕夫 島岡 厳 椿 敦 村上 真 山口 敏章 伊與部 亮 梅山 秀明 木曽 良明

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.9, pp.2487-2493, 1990-09-25 (Released:2008-03-31)

参考文献数

33

被引用文献数

7 11

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The synthesis and the structure-activity relationships of renin inhibitors designed from the angiotensinogen transition state are described. These inhibitors contained residues modified at P1-P1, , P2, and P4-P3. Decrease in the size of side chain alkyl group in norstatine analog at P1 diminished the inhibitory activities of the compounds. Compound 5j, which contained valine residue instead of histidine residue at P2, inhibited potently cathepsin D (IC50=6.0×10-9 M) and pepsin (IC50=3.5×10-7 M) to the same extent as renin (IC50=8.5×10-10 M), and thus was not specific for renin. The reduction of the β-carbonyl group to methylene group in β-carbonylpropionyl residue at P4-P3 decreased the potency about 2 orders against human renin (5i : IC50=1.1×10-7 M vs. 1 : IC50=2.4 ×10-9 M). These results confirmed the rationality of our analysis of the interaction between an orally potent human renin inhibitor 1 and the active site of human renin using modeling techniques, showing that 1 fits the active site of renin favorably. The experimental details of the synthesis are presented.