KINDAI UNIVERSITY


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OUCHI Hidekazu

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FacultyDepartment of Pharmacy
PositionProfessor
Degree
Commentator Guidehttps://www.kindai.ac.jp/meikan/749-oouchi-hidekazu.html
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Last Updated :2020/09/30

Education and Career

Education

  •  - 1995 , Tohoku Pharmaceutical University, Graduate School, Division of Pharmaceutical Sciences
  •  - 1990 , Tohoku Pharmaceutical University, Faculty of Pharmaceutical Science

Academic & Professional Experience

  •   2013 04 ,  - 現在, Professor, Faculty of Pharmacy, Kinki University
  •   2009 04 ,  - 2013 03 , Professor, Faculty of Pharmacy, Aomori Univetsity
  •   2007 04 ,  - 2009 03 , Associate Professor, Faculty of Pharmacy, Aomori Univetsity
  •   2006 04 ,  - 2007 03 , Associate Professor, Faculty of Pharmacy, Aomori Univetsity
  •   2005 04 ,  - 2006 03 , Lecturer, Faculty of Pharmacy, Aomori Univetsity
  •   2005 02 ,  - 2005 03 , Lecturer, Faculty of Pharmacy, Tohoku Pharmaceutical University
  •   1995 04 ,  - 2005 01 , Assistant Professor, Faculty of Pharmacy, Tohoku Pharmaceutical University
  •   2006 ,  - 2009 , Associate Professor, Faculty of Pharmaceutical Sciences, Aomori University
  •   2009 , - Professor, Faculty of Pharmaceutical Sciences, Aomori University
  •   2005 ,  - 2006 , Lecturer, Faculty of Pharmaceutical Sciences, Aomori University
  •   1995 ,  - 2005 , Research Associate, Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutial University
  •   2005 , Lecturer, Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutial University

Research Activities

Research Areas

  • Life sciences, Pharmaceuticals - chemistry and drug development

Research Interests

  • Medicinal Chemistry, Heterocyclic Chemistry, Synthetic Organic Chemistry

Published Papers

  • Synthetic and in vitro studies to indicate that the structure of the PTP1B inhibitor isolated from Acanthopanax senticosus requires reinvestigation, Noshita Toshiro, Onishi Ryoya, Miura Kaori, Hamada Yoshitomo, Nishino Yuki, Ouchi Hidekazu, Tai Akihiro, PHYTOCHEMISTRY LETTERS, PHYTOCHEMISTRY LETTERS, 27, 214 - 218, Oct. 2018 , Refereed
  • Removal of Radioactive Cesium from Soil by Ammonium Citrate Solution and Ionic Liquid, Shunji ISHIWATA, Atsushi TAGA, Fumihiko OGATA, Manabu KITAKOUJI, Hidekazu OUCHI, Hirokuni YAMANISHI, Masayo INAGAKI, Journal of Smart Processing, Journal of Smart Processing, 4(6), 294 - 297, Jun. 2015 , Refereed
  • Regioselective Aromatic Substitution of 6,8-Dihydroxy-4-ethoxycarbonyl-2H-isoquinolin-1-one Derivatives Using the Stille Coupling Reaction, Hidekazu OUCHI, Yoko KAWATA, Mikako ONO, Yasuo MORITA, Yutaka YAMAMOTO, Hiroki TAKAHATA, Heterocycles, Heterocycles, 62(1), 491 - 502, Jan. 2004 , Refereed
  • Synthesis of Azaphenanthrene Derivatives Using Ring-transformation of 4H-1,3-Oxazin-4-one Derivatives, Hidekazu OUCHI, Yoko KAWATA, Yasuo MORITA, Yutaka YAMAMOTO, Hiroki TAKAHATA, Journal of Tohoku Pharmaceutical University, Journal of Tohoku Pharmaceutical University, (50), 75 - 79, Dec. 2003 , Refereed
  • Reactions of Di-tert-butyl Dicarbonate with Benzodiazines and Synthetic Applications of the Products, Hidekazu OUCHI, Yukako SAITO, Noriko Koriyama, Yutaka YAMAMOTO, Annual Report of Tohoku College of Pharmacy, Annual Report of Tohoku College of Pharmacy, 45(45), 111 - 116, Dec. 1998 , Refereed
  • Simple and Mild Method for Preparation of a-Pyridinecarboxylates and a-Pyridyl Ketones via Trimethylstannyl Derivatives,, Yutaka YAMAMOTO, Hidekazu OUCHI, Takuo TANAKA, Chemical & Pharmaceutical Bulletin, Chemical & Pharmaceutical Bulletin, 43(6), 1028 - 1030, Jun. 1995 , Refereed
  • Studies on Organometallic Compounds. VII. Reaction of Di-tert-butyl Dicarbonate with a-Trialkylstannyl Derivatives of Pyridine, Quinoline, and Isoquinoline, Yutaka YAMAMOTO, Hidekazu OUCHI, Takuo TANAKA, Chemical & Pharmaceutical Bulletin, Chemical & Pharmaceutical Bulletin, 43(6), 916 - 919, Jun. 1995 , Refereed
  • Reaction of 2-Trimethylstannylpyridine, -quinoline, and 1-Trimethylstannylisoquinoline with Di-tert-butyl Dithiol Dicarbonate, Yutaka YAMAMOTO, Hidekazu OUCHI, Annual Report of Tohoku College of Pharmacy, Annual Report of Tohoku College of Pharmacy, (41), 79 - 82, Dec. 1994 , Refereed
  • Peripheral gabapentin regulates mosquito allergy-induced itch in mice, Tasuku Akiyama, Tsugunobu Andoh, Eiji Ohtsuka, Hiroshi Nojima, Hidekazu Ouchi, Hiroki Takahata, Yasushi Kuraishi, European Journal of Pharmacology, European Journal of Pharmacology, 833, 44 - 49, Aug. 15 2018 , Refereed
    Summary:The antipruritic activity of gabapentin, an anticonvulsant, was studied in a mouse model of allergic itch. In mice sensitized by an extract of the salivary glands of the mosquito (ESGM), an intradermal injection of ESGM elicited scratching and increased peripheral nerve firing. Oral or intradermal administration of gabapentin at the ESGM injection site inhibited ESGM-induced scratching and peripheral nerve firing. However, gabapentin did not affect histamine-induced scratching. The distributions of immunoreactivity to the voltage-dependent calcium channel α2δ-1 subunit, a site of gabapentin action, and the histamine H1 receptor differed in the mouse dorsal root ganglia. The α2δ-1 subunit was mainly found in neurons that were 15–20 µm in diameter, whereas the H1 receptor was mainly in 20–30 µm neurons. In addition, α2δ-1 subunit immunoreactivity co-localized with that of transient receptor potential vanilloid 1 (TRPV1). These results suggest that gabapentin regulates allergic itch by acting on the calcium channel α2δ-1 subunit in peripheral TRPV1-positive neurons.
  • Structure–activity relationships of flavanones, flavanone glycosides, and flavones in anti-degranulation activity in rat basophilic leukemia RBL-2H3 cells, Toshiro Noshita, Kaori Miura, Kaoru Ikeda, Hidekazu Ouchi, Takuya Matsumoto, Akihiro Tai, Journal of Natural Medicines, Journal of Natural Medicines, 72(2), 551 - 556, Mar. 01 2018 , Refereed
    Summary:The incidence of type I allergies, which are associated with mast cell degranulation and local inflammation, is increasing, and new treatments are needed. To date, structure–activity relationships of flavonoids in their degranulation-inhibiting activity have not been systematically characterized. In the current study, the degranulation-inhibiting activity of a series of flavonoids was evaluated. The following three observations were made: (1) the activity disappears when a sugar moiety is introduced into the A ring of the flavanone (2) the activity depends on the number of hydroxyl groups on the B ring (3) the activity is markedly enhanced when a double bond is introduced into the C ring. The information obtained in the current study may guide the development of a therapy for type I allergies.
  • The structure proposed for apteniol D is different from that of the compound obtained by total synthesis, Toshiro Noshita, Kohei Matsumoto, Hikaru Nishikawa, Hidekazu Ouchi, Yoshitomo Hamada, Akiko Saito, Teiko Yamada, NATURAL PRODUCT RESEARCH, NATURAL PRODUCT RESEARCH, 31(2), 163 - 168, 2017 , Refereed
    Summary:We describe the synthesis of 4,4'-oxyneolignan, the proposed structure for naturally occurring apteniol D. The diphenyl ether moiety in 4,4'-oxyneolignan was formed via classical Ullmann ether synthesis using excess copper powder in N,N-dimethylacetamide. The spectral data of synthesised apteniol D show differences compared to those of naturally occurring apteniol D. [GRAPHICS] .
  • Synthesis and degranulation-inhibiting activities of the proposed apteniols B, C, and G, Toshiro Noshita, Akihiro Tai, Hikaru Nishikawa, Kaoru Ikeda, Hidekazu Ouchi, Yoshitomo Hamada, Akiko Saito, Teiko Yamada, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 79(11), 1743 - 1749, 2015 , Refereed
    Summary:The synthesis of compounds with the structures proposed for the oxyneolignan apteniols B, C, and G is described. The diphenyl ether skeletons of the proposed apteniols were formed via Ullmann ether synthesis. In particular, the spectral data for the synthesized apteniols B, C, and G did not agree with those previously reported for the isolated compounds. Furthermore, the synthesized proposed apteniol B did not show degranulation-inhibiting activity, while the prepared proposed apteniols C and G exhibited activities considerably weaker than that of the methyl ester of proposed apteniol A.
  • Syntheses and biological activities of the proposed structure of apteniol A and its derivatives, Hikaru Nishikawa, Toshiro Noshita, Akihiro Tai, Hidekazu Ouchi, Taisuke Okamoto, Akiko Saito, Teiko Yamada, Atsuko Iomori, Nao Ishimata, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 78(9), 1485 - 1489, Sep. 2014 , Refereed
    Summary:We describe the syntheses of the proposed structure of diphenyl ether oxyneolignan, apteniol A and its derivatives. The diphenyl ether moiety of proposed apteniol A was formed via Ullmann ether synthesis, but the spectral data of the synthesized apteniol A did not agree with that in previous studies. The dimethyl ester derivative of the proposed apteniol A was found to enhance neurite outgrowth in PC12 cells and inhibit antigen-induced degranulation in RBL-2H3 cells.
  • Carboxamidation of carboxylic acids with 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline (BBDI) without bases, Yukako Saito, Hidekazu Ouchi, Hiroki Takahata, TETRAHEDRON, TETRAHEDRON, 64(49), 11129 - 11135, Dec. 2008 , Refereed
    Summary:Formation of carboxamides of a variety of carboxylic acids with the coupling reagent BBDI is described, This procedure permits a one pot and simple operation without the need of any bases and no base was required for even use of amine hydrochlorides. In addition, an approach to BBDI-catalyzed carboxamidation is examined. (C) 2008 Elsevier Ltd. All rights reserved.
  • Asymmetric synthesis of all stereoisomers of isofagomine using [2,3]-Wittig rearrangement, Yukiko Mihara, Hidetomo Ojima, Tatsushi Imahori, Yuichi Yoshimura, Hidekazu Ouchi, Hiroki Takahata, HETEROCYCLES, HETEROCYCLES, 72(1), 633 - 645, Apr. 2007 , Refereed
    Summary:The asymmetric synthesis of all stereoisomers of isofagornine from 5-hydroxymethyl-3-piperidene 6, which was prepared by [2,3]-Wittig rearrangement of O-alkylstannylmethyl compound 5 derived from readily available chiral 3-hydroxypiperidene 4, is described.
  • A new preparation of homochiral N-protected 5-hydroxy-3-piperidenes, promising chiral building blocks, by palladium-catalyzed deracemization of their alkyl carbonates, Hiroki Takahata, Yurniko Suto, Erina Kato, Yuichi Yoshimura, Hidekazu Ouchi, ADVANCED SYNTHESIS & CATALYSIS, ADVANCED SYNTHESIS & CATALYSIS, 349(4-5), 685 - 693, Mar. 2007 , Refereed
    Summary:The palladium-catalyzed deracemization of N-protected alkyl carbonates of 5-hydroxy-3-piperidenes by use of chiral phosphine ligands is described. A Trost ligand such as (R)-BPA was found to be a suitable chiral ligand for the deracemization, providing N-protected 5-hydroxy-3-piperidenes in good yields with good to high enantioselectivities. A plausible mechanism for the reaction is proposed.
  • A novel tert-butoxycarbonylation reagent: 1-tert-butoxy-2-tertbutoxycarbonyl-1,2-dihydroisoquinoline (BBDI), Yukako Saito, Hidekazu Ouchi, Hiroki Takahata, TETRAHEDRON, TETRAHEDRON, 62(50), 11599 - 11607, Dec. 2006 , Refereed
    Summary:The use of 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline (BBDI) as a tert-butoxycarbonylation reagent for acidic proton-containing substrates such as phenols, aromatic and aliphatic amines hydrochlorides, and aromatic carboxylic acids in the absence of a base is described. The reactions proceed chemoselectively in high yield under mild conditions. (c) 2006 Elsevier Ltd. All fights reserved.
  • Synthesis of novel 5-acetoacetyl-3-acetyl-2-pyridone derivatives by the ring-transformation of 6-methyl-1,3-oxazin-4-ones, Hidekazu Ouchi, Hisao Saito, Yutaka Yamamoto, Hiroki Takahata, Heterocycles, Heterocycles, 66(1), 299 - 308, Dec. 31 2005 , Refereed
    Summary:The synthesis of novel poly-functionalized 5-acetoacetyl-3-acetyl-2-pyridone derivatives was achieved via the ring-transformation of 6-methyl-4H-1,3-oxazin-4-ones with 3-methylisoxazole derivatives, followed by reductive cleavage of the isoxazole ring and hydrolysis. © 2005 The Japan Institute of Heterocyclic Chemistry.
  • A new route to diverse 1-azasugars from N-boc-5-hydroxy-3-piperidene as a common building block, H Ouchi, Y Mihara, H Takahata, JOURNAL OF ORGANIC CHEMISTRY, JOURNAL OF ORGANIC CHEMISTRY, 70(13), 5207 - 5214, Jun. 2005 , Refereed
    Summary:A new general method for the synthesis of a variety of 1-azasugars with a nitrogen atom at the anomeric position is described. The readily available chiral N-Boc-5-hydroxy-3-piperidene 3 is transformed to isofagomine (2), homoisofagomine (13), and 5'-deoxyisofagomine (14) via stereo-selective epoxidation and regioselective ring-cleavage in a highly stereocontrolled manner. In addition, the synthesis of all four stereoisomers of 3,4,5-trihydroxypiperidines (18-21) classified as 1-azasugar-type glycosidase inhibitors was stereoselectively achieved from the (chiral) piperidene 3.
  • Biological properties of D- and L-1-deoxyazasugars, A Kato, N Kato, E Kano, Adachi, I, K Ikeda, L Yu, T Okamoto, Y Banba, H Ouchi, H Takahata, N Asano, JOURNAL OF MEDICINAL CHEMISTRY, JOURNAL OF MEDICINAL CHEMISTRY, 48(6), 2036 - 2044, Mar. 2005 , Refereed
    Summary:L-Enantiomers of 1-deoxynojirimycin (DNJ), 1-deoxymannojirimycin (manno-DNJ), 1-deoxyallonojirimycin (allo-DNJ), 1-deoxyaltronojirimycin (altro-DNJ), 1-deoxygalactonojirimycin (galacto-DNJ), 1-deoxygulonojirimycin (gulo-DNJ), and 1-deoxyldonojirimycin (ido-DNJ) were prepared according to prior methods for the D-enantiomers. These enantiospecific syntheses established unambiguously the absolute configuration of naturally occurring DNJ, manno-DNJ, allo-DNJ, altro-DNJ, and gulo-DNJ. Although D-DNJ and D-galacto-DNJ are known to be powerful competitive inhibitors of alpha-glucosidase and alpha-galactosidase, respectively, with K-i values in the nM range, L-DNJ and L-galacto-DNJ were noncompetitive inhibitors of alpha-glucosidase and alpha-galactosidase, respectively, with K-i values in the PM range. However, the azasugar mimicking the structure of the terminal sugar moiety of the natural substrate is not always an inhibitor of the glycosidase responsible for the hydrolysis. D-manno-DNJ is known as a much better inhibitor of alpha-L-fucosidase than a-mannosidase, while L-allo-DNJ was a better inhibitor than D-manno-DNJ of alpha-mannosidase. L-galacto-DNJ can be regarded as the 6-hydroxylated derivative of deoxyfuconojirimycin (DFJ), which is a powerful inhibitor of alpha-L-fucosidase with a K-i value in the nM range. However, this replacement of the methyl group in DFJ by a hydroxymethyl group reduced its affinity by about 50-fold. This suggests that there is a hydrophobic region in or around the active site of alpha-L-fucosidase. It has been found that inhibitors of human lysosomal glycosidases have therapeutic potential for the corresponding lysosomal storage diseases (Nat. Med. 1999, 5, 112; Proc. Natl. Acad. Sci. USA, 2002, 99, 15428). Inhibition of human lysosomal glycosidases by the 1-deoxyazasugars synthesized was investigated. D-galacto-DNJ is a potent inhibitor of lysosomal alpha-galactosidase (IC50 = 90 nM) and is now being evaluated preclinically for its potential use in Fabry disease, while D-DNJ inhibiting alpha-glucosidase (IC50 = 40 nM) potently does not appear to become a potential therapeutic agent because of additional inhibitory activity toward glycoprotein processing alpha-glucosidases. On the other hand, although L-allo-DNJ is a moderate inhibitor of alpha-mannosidase (IC50 = 64 mu M), it may become a key compound for the drug design of potential therapeutic agents for alpha-mannosidosis.
  • Simple and mild esterification of N-protected amino acids with nearly equimolar amounts of alcohols using 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline, Y Saito, T Yamaki, F Kohashi, T Watanabe, H Ouchi, H Takahata, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 46(8), 1277 - 1279, Feb. 2005 , Refereed
    Summary:A very mild, one-step esterification using nearly equimolar amounts of N-protected amino acids and alcohols, in conjunction with 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline (BBDI) as a novel condensing reagent is described. (C) 2005 Elsevier Ltd. All rights reserved.
  • The L-enantiomers of D-sugar-mimicking iminosugars are noncompetitive inhibitors of D-glycohydrolase?, N Asano, K Ikeda, L Yu, A Kato, K Takebayashi, Adachi, I, Kato, I, H Ouchi, H Takahata, GWJ Fleet, TETRAHEDRON-ASYMMETRY, TETRAHEDRON-ASYMMETRY, 16(1), 223 - 229, Jan. 2005 , Refereed
    Summary:1,4-Dideoxy-1,4-imino-L-arabinitol (L-AB1) and 2,5-dideoxy-2,5-imino-L-mannitol (L-DMDP) are much more potent inhibitors of isomaltase than their D-enantiomers. D-Enantiomers inhibited isomaltase in a competitive manner. whereas L-enantiomers were noncompetitive inhibitors of the enzyme. Similarly D-isofagomine and L-isofagomine were competitive and noncompetitive inhibitors of human lysosomal beta-D-glucosidase (beta-glucocerebrosidase), with K-i values of 0.016 and 5.7 muM, respectively. The multiple inhibition analysis of beta-glucocerebrosidase by D-isofagomine and L-isofagomine indicated that the D-enantiomer best fits the catalysis site of beta-glucocerebrosidase. while the L-enantiomer has a favorable interaction with a regulatory site other than the active site. Our recent and present results suggest that D-iminosugars are competitive inhibitors Of D-glycohydrolases but their L-enantiomers are noncompetitive inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.
  • Asymmetric synthesis of all six regioisomers of N-boc-dimethylphenylalanines, H Ouchi, M Kumagai, S Sakurada, H Takahata, HETEROCYCLES, HETEROCYCLES, 64, 505 - 514, Dec. 2004 , Refereed
    Summary:All possible regioisomers of dimethyl-substituted (S)-phenylalanine were efficiently synthesized by reacting the NI(Il)-complex of the chiral Schiff base of glycine with (S)-2-N-(N-benzylprolyl)aminobenzophenone.
  • A short and concise synthesis of isofagomine, homoisofagomine, and 5 '-deoxyisofagomine, H Ouchi, Y Mihara, H Watanabe, H Takahata, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 45(38), 7053 - 7056, Sep. 2004 , Refereed
    Summary:A short and concise synthesis of isofagomine derivatives via the epoxidation of chiral N-Boc-5-hydroxy-3-piperidene, followed by regioselective epoxide ring opening is described. This constitutes the first reported synthesis of homoisofagomine and the 5'-deoxyisofagomine. (C) 2004 Elsevier Ltd. All rights reserved.
  • Concise and highly stereocontrolled synthesis of 1-deoxygalactonojirimycin and its congeners using dioxanylpiperidene, a promising chiral building block, H Takahata, Y Banba, H Ouchi, H Nemoto, ORGANIC LETTERS, ORGANIC LETTERS, 5(14), 2527 - 2529, Jul. 2003 , Refereed
    Summary:[GRAPHICS] A concise and stereoselective synthesis of the chiral building block, dioxanylpiperidene 4 as a precursor for deoxyazasugars, starting from the Garner aldehyde 5 using catalytic ring-closing metathesis (RCM) for the construction of the piperidine ring is described. The asymmetric synthesis of 1-deoxygalactonojirimycin and its congeners 1-3 was carried out via the use of 4 in a highly stereocontrolled mode.
  • Asymmetric synthesis of the four possible fagomine isomers, H Takahata, Y Banba, H Ouchi, H Nemoto, A Kato, Adachi, I, JOURNAL OF ORGANIC CHEMISTRY, JOURNAL OF ORGANIC CHEMISTRY, 68(9), 3603 - 3607, May 2003 , Refereed
    Summary:The asymmetric synthesis of fagomine and its congeners 1-4 has been achieved by catalytic ring-closing metathesis (RCM). The synthesis involved the construction of the piperidene-type chiral building block 5 followed by dihydroxylation, starting from the D-serine-derived Garner aldehyde 6.
  • Suppression by gabapentin of pain-related mechano-responses in mice given orthotopic tumor inoculation, Y Kuraishi, Y Iida, HW Zhang, S Uehara, H Nojima, J Murata, Saiki, I, H Takahata, H Ouchi, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 26(4), 550 - 552, Apr. 2003 , Refereed
    Summary:In this study, we examined whether several types of non-opioid agents would inhibit the pain-related responses of melanoma-bearing mice. Orthotopic inoculation with melanoma into the hind paw induced marked tactile allodynia and mechanical hyperalgesia. A peroral injection (p.o.) of gabapentin (100-300 mg/kg) inhibited the allodynia and hyperalgesia, without effects on gross behaviors. An intraperitoneal injection (i.p.) of ketamine hydrochloride (30 mg/kg) produced partial inhibition in allodynia and hyperalgesia and prostate posture at 15 min after injection. Diclofenac sodium (10 and 30 mg/kg, i.p), mexiletine hydrochloride (20 mg/kg, i.p.), clonidine hydrochloride (0.1 mg/kg, i.p.) and suramin (100 mg/kg, i.p.) were without effects on allodynia and hyperalgesia. Subcutaneous injections of baclofen (3 mg/kg) and N-G-nitro-L-arginine methyl ester (100 mg/kg) were also without effects. Repeated administration of gabapentin (150 mg/kg, p.o.) produced constant inhibitions, suggesting no analgesic tolerance. Gabapentin may be useful for the management of cancer pain.
  • A novel C-2-symmetric 2,6-diallylpiperidine carboxylic acid methyl ester as a promising chiral building block for piperidine-related alkaloids, H Takahata, H Ouchi, M Ichinose, H Nemoto, ORGANIC LETTERS, ORGANIC LETTERS, 4(20), 3459 - 3462, Oct. 2002 , Refereed
    Summary:[GRAPHICS] C-2-Symmetric 2,6-diallyipiperidine 1-carboxylic acid methyl ester (5) was examined via the double asymmetric allylboration of glutaraldehyde followed by aminocyclization and carbamation as a promising chiral building block for piperidine-related alkaloids, which were synthesized by the desymmetrization of 5 using intramolecular iodocarbamation as a key step.
  • Dermorphin and deltorphin heptapeptide analogues: Replacement of Phe residue by Dmp greatly improves opioid receptor affinity and selectivity, Akihiro Ambo, Harumi Murase, Hideko Niizuma, Hidekazu Ouchi, Yutaka Yamamoto, Yusuke Sasaki, Bioorganic and Medicinal Chemistry Letters, Bioorganic and Medicinal Chemistry Letters, 12(6), 879 - 881, Mar. 25 2002 , Refereed
    Summary:The usefulness of 2,6-dimethylphenylalanine (Dmp) as a Phe surrogate in two opioid peptides, dermorphin (DM) and deltorphin II (DT), was investigated. Compared to DM, [L-Dmp3]DM (1) showed a 170-fold increase in μ affinity and only a 4-fold increase in δ affinity, resulting in a 40-fold improvement in μ receptor selectivity. Compared to DT, [L-Dmp3]DT (3) showed a 22-fold increase in δ affinity and somewhat of a loss in μ affinity, and consequently a marked (75-fold) improvement in δ receptor selectivity. The D-Dmp replacement, however, resulted in a great loss in receptor selectivity in each of the peptides. The specific receptor interactions of 1 and 3 were confirmed by in vitro bioassays. Analogues 1 and 3 seem to be useful as pharmacological tools for the study of opioid systems. © 2002 Elsevier Science Ltd. All rights reserved.
  • 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline: A novel and chemoselective tert-butoxycarbonylation reagent, H Ouchi, Y Saito, Y Yamamoto, H Takahata, ORGANIC LETTERS, ORGANIC LETTERS, 4(4), 585 - 587, Feb. 2002 , Refereed
    Summary:[GRAPHICS] The use of 1-tert-butoxy-2-tertbutoxycarbonyl-1,2-dihydroisoquinoline (BBDI) as tertbutoxycarbonylation reagent for aromatic and aliphatic amine hydrochlorides and phenols in the absence of a base has been demonstrated. The reactions proceed chemoselectively in high yield under mild conditions.
  • Enkephalin analogues with 2 ',6 '-dimethylphenylalanine replacing phenylalanine in position 4, Y Sasaki, M Hirabuki, A Ambo, H Ouchi, Y Yamamoto, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 11(3), 327 - 329, Feb. 2001 , Refereed
    Summary:Four Leu-enkephalin (Enk) analogues containing 2'.6'-dimethyphenylalanine (Dmp) in position 4 were prepared and tested for their receptor binding and biological activities. Among the analogues prepared, [2', 6'-dimethvltyrosine(1), D-Dmp(4)]Enk was found to be an antagonist toward mu and delta opioid receptors with pA(2) values of 6.90 and 5.57, respectively. (C) 2001 Elsevier Science Ltd. All rights reserved.
  • Biological properties of opioid peptides replacing Tyr at position 1 by 2,6-dimethyl-Tyr, Y Sasaki, T Suto, A Ambo, H Ouchi, Y Yamamoto, CHEMICAL & PHARMACEUTICAL BULLETIN, CHEMICAL & PHARMACEUTICAL BULLETIN, 47(10), 1506 - 1509, Oct. 1999 , Refereed
    Summary:To understand the effect of the replacement of Tyr residue at position 1 in opioid peptides by 2,6-dimethyl-Tyr (Dmt) on the biological property, chiral (D or L) Dmt(1) analogs of Leu-enkephalin (Enk) and Tyr-D-Arg-Phe-beta Ala-NH2 (YRFB) were synthesized and their enzymatic stabilities, irt vitro bioactivities and receptor binding affinities compared with those of parent peptides, [L-Dmt(1)]Enk (1) exhibited 4-fold higher stability against aminopeptidase-IM and possessed dramatically increased activities in guinea pig ilium (GPI) (187-fold) and mouse vas deferens (MVD) (131-fold) assays, and in rat brain receptor binding assays (356-fold at mu receptor and 46-fold at delta receptor) as compared to Enk [L-Dmt(1)]YRFB (3) also exhibited increased activities in GPI (46-fold) and MVD (177-fold) assays, and in the binding assays (69-fold at mu receptor and 341-fold at delta receptor) as compared to the parent peptide. [D-Dmt(1)]Enk (2) and [D-Dmt(1)]YRFB (4) exhibited activities with diminished or lesser potency than the parent peptide in all assays. These results indicate that there is a tendency for mu affinity to be enhanced more than delta affinity with introduction of L-Dmt into delta ligand peptide (Enk), and for delta affinity to be enhanced more than ill affinity in case of mu ligand peptide (YRFB), resulting in reduced receptor selectivities at the receptors.
  • DIRECT INTRODUCTION OF ACYL AND ETHOXYCARBONYL GROUPS INTO PYRIMIDINE RING THROUGH THE TRIMETHYLSTANNYL DERIVATIVES, Y YAMAMOTO, H OUCHI, T TANAKA, Y MORITA, HETEROCYCLES, HETEROCYCLES, 41(6), 1275 - 1290, Jun. 1995 , Refereed
    Summary:The reactions of acylformyl chlorides with 2- and 4-trimethylstannylpyrimidine derivatives proceeded more smoothly than those of acyl chlorides giving the corresponding 2- and 4-acylpyrimidines. Employing ethyl chlorogly-oxylate in stead of the acylating agent yielded the ethoxycarbonylpyrimidines. Similarly, the stepwise acylation and ethoxycarbonylation of bis(trimethylstannyl)-pyrimidines provided pyrimidines having two different carbon functional groups.
  • CARBON FUNCTIONALIZATIONS ON PYRIDINE RING VIA TRIMETHYLSTANNYL DERIVATIVES - AN EXAMPLE OF FUSARIC ACID SYNTHESIS, Y YAMAMOTO, T TANAKA, H OUCHI, M MIYAKAWA, Y MORITA, HETEROCYCLES, HETEROCYCLES, 41(4), 817 - 825, Apr. 1995 , Refereed
    Summary:Method for introduction of two types of carbon functional groups, acyl and tert-butoxycarbonyl groups, in pyridine ring via bis(trimethylstannyl) pyridine (1) is explored. Application of this method to the synthesis of fusaric add (11) is also described.

Research Grants & Projects

  • Development of functional reagent using heterocyclic compound
  • Study on synthesis and design of the bioactive molecules