著者

藤井 澄三 小川 和男 板谷 泰助 伊達 忠正 稲垣 甚一郎 野原 富士夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.3, pp.408-413, 1995-03-15 (Released:2008-03-31)

参考文献数

25

被引用文献数

2 3

---

A full account is given of the first syntheses of 6-mercaptopurine 7-N-oxide (4) and 6-methylthiopurine 7-N-oxide (5). The synthesis of 4 followed a "phenacylamine route", which started from condensation of 4, 6-dichloro-5-nitropyrimidine (15) with N-(4-methoxybenzyl)phenacylamine to form the phenacylaminopyrimidine derivative (11) and proceeded through conversion into the mercapto derivative, intramolecular cyclization between the NO2 nitrogen atom and the phenacyl carbanion to give 6-mercapto-9-(4-methoxybenzyl)purine 7-N-oxide (12), and removal of the 4-methoxybenzyl group. S-Methylation of 12 and removal of the 4-methoxybenzyl group afforded 5. The location of the oxygen function in 4, 5, and 12 was confirmed by X-ray crystallographic analysis of 5·H2O, which was shown to exist in the N(7)-OH form (19). A UV spectroscopic approach suggested that the neutral species of 4 exists in HO as the N(7)-OH tautomer (21), whereas that of 5 exists as an equilibrated mixture of the N(7)-oxide (5) and the N(7)-OH (19) tautomers. In the in vitro bioassay of antileukemic activity against murine L5178Y cells, the N-oxides 4 and 12 were found to be weakly cytotoxic.

著者

板谷 泰助 小川 和男 松本 浩郎 渡辺 朝子

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.28, no.9, pp.2819-2824, 1980-09-25 (Released:2008-03-31)

参考文献数

11

被引用文献数

7 8

---

Heating N, N-diethyl-3, 9-dialkyladeninium halides (Ig-j) in aqueous sodium hydroxide gave 1-alkyl-5-(alkylamino)imidazole-4-carboxamides (IV) together with minor amounts of 1-alkyl-5-(alkylamino)imidazole-4-carbonitriles (III), which were converted into IV on further heating. N, N-Dimethyl-3, 9-dialkyladeninium halides (Ia-d) underwent hydrolysis more rapidly to provide IV selectively in 90-94% yields.

著者

藤井 澄三 小川 和男 斎藤 徹 板谷 泰助 伊藤 忠正 岡村 公生

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.2, pp.321-324, 1995-02-15 (Released:2008-03-31)

参考文献数

26

---

Oxidation of 1-benzyladenine (12) with m-chloroperoxybenzoic acid in MeOH or in MeOH-0.5 M phosphate buffer (pH 6.6) has been found to afford 1-benzyladenine 7-oxide (13) as the main product. Nonreductive debenzylation of 13 gave adenine 7-oxide (14) in 63% yield. The structure of 13 was unequivocally established by an X-ray crystallographic analysis.

著者

/ 藤井 澄三 斎藤 徹 TOHRU SAITO

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.34, no.5, pp.2037-2043, 1986-05-25 (Released:2008-03-31)

参考文献数

28

被引用文献数

9 14

---

A detailed account is given of the final step of the general 7-alkalation procedure for adenine (1), which consists of the preferential benzylation at the 3-position of 1, regioselective alkylation of the resulting 3-benzyladenine (2) to give 7-alkyl-3-benzyladenine salts (3a-c), and debenzylation of 3a-c leading to 7-alkyladenines (4a-c). Debenzylation of 3a-c (X=Cl or ClO4) has been achieved by hydrogenolysis using hydrogen and Pd-C catalyst at atmospheric pressure, producing 7-alkyladenines (4a-c) in 38-74% yields. The use of the allyl or γ, γ-dimethylallyl group at the 3-position instead of the benzyl group for the synthesis of 7-methyladenine (4a) by this procedure has no practical value. Alternatively, the salts 3a-c (X=Br, ClO4, or I) have been debenzylated efficiently by treatment with conc. H2SO4 in the presence of toluene at room temperature for 3-6h or at 60°C for 0.5-2h, giving 4a-c in 73-93% yields.

著者

藤井 澄三 小川 和男 斎藤 徹 小林 恵子 板谷 泰助 伊達 忠正 岡村 公生

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.1, pp.53-62, 1995-01-15 (Released:2008-03-31)

参考文献数

49

被引用文献数

3 4

---

A detailed account is given of the first unequivocal synthesis of adenine 7-oxide (8). The synthesis started with peroxycarboxylic acid oxidation of 3-benzyladenine (6), readily obtainable from adenine (1) by benzylation, and proceeded through nonreductive debenzylation of the resulting 3-benzyladenine 7-oxide (7). The location of the oxygen function in 7 and 8 was confirmed by their chemical reactions including deamination and methylation and by X-ray crystallographic analysis. A UV spectroscopic approach suggested that the neutral species of 8 exists in H2O as an equilibrated mixture of the N(7)-oxide (8) and N(7)-OH (21) tautomers. Treatment of 6 with 30% aqueous H2O2 in MeOH in the presence of MeCN and KHCO3 at 30°C produced the N(7)-oxide 7 and 7-acetamido-3-benzyladenine (15) in 12% and 1% yields, respectively.

著者

小川 和男 西井 正廣 稲垣 甚一郎 野原 富士夫 斎藤 徹 板谷 泰助 藤井 澄三

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.5, pp.1315-1317, 1992-05-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

2 7

---

The synthesis of 8-methylguanine 7-oxide (3) was accomplished via a "phenacylamine route", which started from condensation of α-(4-methoxybenzylamino)propiophenone (6), prepared by coupling of α-bromopropiophenone (4) and 4-methoxybenzylamine (5), with 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone (7) and proceeded through cyclization of the resulting phenacylaminopyrimidinone (8) and removal of the 4-methoxybenzyl group. The N-oxide 3 and its 9-arylmethyl derivatives 9 and 11 showed only very weak antileukemic activity and no antimicrobial activity.

著者

小川 和男 西井 正廣 稲垣 甚一郎 野原 富士夫 斎藤 徹 板谷 泰助 藤井 澄三

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.2, pp.343-350, 1992-02-25 (Released:2008-03-31)

参考文献数

47

被引用文献数

8 10

---

A full account is given of the first chemical synthesis of the antitumor antibiotic guanine 7-oxide (5) and its 9-substituted derivatives (24a-k and 26). Coupling of appropriate primary amines (17a-e, g-k) with phanecyl bromide (16) produced, after treatment with HCl, the corresponding N-substituted phenacylamine hydrochlorides (18a-e, g-k). A similar phenacylation of 4-amino-1-butanol (21) failed to give the desired compound 18f, so that 21 was heated with 2-bromomethyl-2-phenyl-1, 3-dioxolane (20) at 150-155°C for 3h to furnish, after treatment with HCl, the amino ketal hydrochloride 22 in 40% yield. Deketalization of 22 with hot 2N aqueous HCl afforded 18f in 96% yield. Condensations of the free bases, generated in situ from the hydrochlorides 18a-l and 1N aqueous NaOH, with the chloropyrimidinone 6 were effected in aqueous EtOH at the boiling point for 20 min or at 25-30°C for 3-24h, giving the 6-phenacylamino-4-pyrimidinones 19a-l in 54-90% yields. On treatment with 2N aqueous NaOH at room temperature for 10-60 min, the nitropyrimidinones 19a-k cyclized to provide the 9-substituted guanine 7-oxides 24a-k in 61-98% yields. A similar alkali-treatment of 19l failed to yield guanine 7-oxide (5). However, removal of the 9-(arylmethyl) group from 24i-k was effected with conc, H2SO4 at room temperature for 1-3h in the presence of toluene, producing the target N-oxide 5 in 56-89% yields. In the in vitro bioassay of antileukemic activity against murine L5178Y cells, none of the 9-substituted guanine 7-oxides (24a-k and 26) was more effective than the parent, natural N-oxide 5. Within this series, however, the benzyl analogues 24g-k with or without alkoxy functions were more cytotoxic, with IC50's of 13.0-48.0μg/ml, than the alkyl analogues 24a-f.

著者

板谷 泰助 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.33, no.5, pp.1906-1913, 1985-05-25 (Released:2008-03-31)

参考文献数

32

被引用文献数

2 4

---

Reaction of 1-methyl-5-(methylamino) imidazole-4-carboxamide (6a) with a boiling mixture of ethyl orthoformate and acetic anhydride produced 3, 9-dimethylhypoxanthine (7a) in 60% yield and 1-methyl-5-(N-methylformamido) imidazole-4-carboxamide (5a) in 39% yield. Compound 5a was transformed into 7a by treatment with NaH in 78% yield. Compound 7a was alternatively prepared by cyclocondensation of 6a with diethoxymethane followed by oxidation with I2. The pyrimidine moiety of 7a has been shown to be reactive : 7a affords the 1, 2-dihydro derivative 9 under reductive conditions and undergoes ring opening to 5a in aqueous NaOH. 3-Ethyl-9-methyl-(7b), 3-benzyl-9-methyl-(7c), 9-ethyl-3-methyl-(7d), and 3, 9-dibenzylhypoxanthine (7e) were also prepared from the corresponding carboxamides 6b-e.

著者

板谷 泰助 松本 浩郎 渡辺 朝子 原田 恒博

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.33, no.6, pp.2339-2347, 1985-06-25 (Released:2008-03-31)

参考文献数

34

被引用文献数

10 17

---

Treatment of 5-(methylamino)-1-β-D-ribofuranosylimidazole-4-carboxamide (5a) with CNBr in acetate buffer gave the 5-cyanomethylamino derivative 6a, which was cyclized to 3-methyl-guanosine (7) in the presence of NaOEt. Cyclocondensation of 7 with bromoacetone in the presence of K2CO3 provided 3-β-D-ribofuranosylwye (2), the most probable structure for the fluorescent nucleoside from Torulopsis utilis phenylalanine transfer ribonucleic acid (tRNAPhe). The glycosidic bonds of 2 and 7 have been shown to be unusually subject to cleavage under either acidic or basic conditions, but proved to be less labile under neutral conditions, as had been reported. The base moiety of 2 is also cleaved under basic conditions.

著者

藤井 澄三 高田 泰孝 小川 和男 板谷 泰助 松原 聰

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.2, pp.325-327, 1995-02-15 (Released:2008-03-31)

参考文献数

20

被引用文献数

2

---

Treatment of N6-benzyladenine (2) with 15% aqueous H2O2 in trifluoroacetic acid at 65-70°C for 1 h was found to give the N(3)-oxide (3) and the N(7)-oxide (4) in 4% and 4% yields, respectively. The structure of 3 was established by its identity with a sample prepared from 6-chloropurine 3-oxide (6) and benzylamine, and the structure of 4 by its identity with a sample obtained from 1-benzyladenine 7-oxide (8) by Dimroth rearrangement. The N-oxides 3 and 4, together with previously reported N6-benzyladenine 1-oxide (1), were tested for cytokinin activity in the tobacco callus bioassay. Each of the three N-oxides was active at 4 μM concentration, being less active than the parent base 2 by a factor of 40.

著者

板谷 泰助 小川 和男 松本 浩郎 渡辺 朝子

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.28, no.8, pp.2522-2527, 1980-08-25 (Released:2008-03-31)

参考文献数

10

被引用文献数

3 5

---

The reactions of N, N, 9-trialkyladenines (II) with alkyl halides in N, N-dimethylacetamide gave N, N, 3, 9-tetraalkyladeninium halides (IV) in good yields. N, N, 3-Trialkyl-adenines (III) underwent the alkylation more smoothly to provide an alternative synthesis of IV.

著者

小川 和男 西井 正廣 野原 富士夫 斎藤 徹 板谷 泰助 藤井 澄三

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.3, pp.612-616, 1992-03-25 (Released:2008-03-31)

参考文献数

46

被引用文献数

2 8

---

A detailed account is given of the first chemical synthesis of hypoxanthine 7-N-oxide (5), which started from coupling of 6-chloro-5-nitro-4(3H)-pyrimidinone (7) with N-(4-methoxybenzyl)phenacylamine, generated in situ from the hydrochloride (8), and proceeded through cyclization of the resulting phenacylaminopyrimidinone (9) and removal of the 4-methoxybenzyl group. The results of catalytic hydrogenolysis, methylation followed by catalytic hydrogenolysis, and rearrangement under acidic conditions of 5 supported the correctness of the assigned structure. An ultraviolet spectroscopic approach suggested that the neutral species of 5 exists in H2O mainly as the N(7)-OH tautomer (21). In the in vitro bioassay of antileukemic activity against murine L5178Y cells, 5 was weakly cytotoxic, with IC50 of 100μg/ml. It did not show any antimicrobial activity even at 1000μg/ml. None of the 9-(4-methoxybenxyl) (11) and O-methyl (12, 13, and 14) derivatives was found to be antiieukemic or antimicrobial.

著者

Kentaro Takai Takeshi Enomoto

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.66, no.1, pp.37-44, 2018-01-01 (Released:2018-01-01)

参考文献数

67

被引用文献数

4

---

Among the muscarinic acetylcholine receptor (mAChR) subtypes, the M4 receptor has been investigated as a promising drug target for the treatment of schizophrenia. These investigations have been based on findings from M4-deficient mice studies as well as on the results of a clinical trial that used xanomeline, an M1/M4 mAChRs-preferring agonist. Both orthosteric agonists and positive allosteric modulators of M4 mAChR have been reported as promising ligands that not only have antipsychotic effects, but can also improve cognitive impairment and motor dysfunction. However, challenges remain due to the high homology of the orthosteric binding site among all muscarinic receptors. In this review, we summarize our approach to the identification of M4 mAChR activators, orthosteric agonists, and positive allosteric modulators based on M4 mAChR structural information and structure–activity relationship studies. These findings indicate that selective M4 mAChR activators are promising potential therapeutic agents for several central nervous system conditions.

著者

宮原 一元 伊田 喜光 川崎 敏男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.20, no.11, pp.2506-2510, 1972-11-25 (Released:2008-03-31)

被引用文献数

6 9

著者

佐野 和珠子 真田 修一 伊田 喜光 庄司 順三

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.4, pp.865-870, 1991-04-25 (Released:2008-03-31)

参考文献数

22

被引用文献数

71 91

---

Five new compounds, kalopanaxsaponin G (2) and kalopanaxins A (6), B (8), C (11) and D (13), were isolated from the bark of Kalopanax pictus together with nine known compounds, kalopanaxsaponins A (1) and B (5), pericarpsaponin PJ3 (3), hederasaponin B (4), syringin (7), protocatechuic acid (9), coniferin (10), liriodendrin (=dl-syringaresinol di-O-glucopyranoside) (12), glucosyringic acid (14) and chlorogenic acid (15). The structures of the new compounds were characterized as hederagenin 28-O-α-L-rhamnopyranosyl(1→4)-β-glucopyranosyl(1→6)-β-D-glucopyranoside (2), ferulyldehyde (=coniferylaldehyde) 4-O-β-D-glucopyranoside (6), coniferin 6'-O-(4-O-α-L-rhamnopyranosyl)-syringate (8), 2-methoxyhydroquinone 4-O-[6-O-(4-O-α-L-rhamnopyranosyl)-syringyl]-β-D-glucopyranoside (11) and coniferyl alcohol 4-O-β-D-apiofuranosyl(1→2)-β-D-glucopyranoside (=coniferin 2'-O-β-D-apiofuranoside) (13).

著者

KAZUO IGARASHI FUMIYO KASUYA MIYOSHI FUKUI HISASHI NANJYOU

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.7, pp.3033-3036, 1987-07-25 (Released:2009-10-19)

参考文献数

9

被引用文献数

4 5

---

A high-performance liquid chromatographic (HPLC) method using a fluorescence detector is described for the simultaneous determination of dibucaine and its metabolites (M-4, M-8 and M-10) in human urine. Urine samples from obstetric patients were chromatographed in a reversed-phase system. When a ultraviolet detector (320 nm) was used, some interfering peaks appeared on the chromatogram, but this interference could be overcome by employing a fluorescence detector (Ex 330 nm and Em 440 nm) instead. The calibration curves were linear in the range of 0.05-5.0 μg/ml for all compounds and the detection limits of dibucaine and its metabolites were about 5 ng/ml in urine. The urinary excretion of dibucaine and its metabolites by obstetric patients infused with Percamine S® in the spinal cord were determined. The mean cumulative amounts of dibucaine, M-4, M-8 and M-10 excreted during 10 h after administration were 1.1, 10.5, 3.5 and 1.1 % of the dose, respectively. The total urinary excretion was 16.2% of the dose. This method is sufficiently sensitive and specific to permit the determination of dibucaine and its metabolites in biological fluids.

著者

永吉 剛 佐伯 清太郎 浜名 政和

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.7, pp.1827-1831, 1981-07-25 (Released:2008-03-31)

参考文献数

27

被引用文献数

4 5

---

Treatment of 1-hydroxy-2-phenylindole (1) with phosphoryl chloride-DMF gave 2-phenylindole-3-carboxaldehyde (2) in 70% yield. The reaction of 1 with quinoline 1-oxide (3) and benzoyl chloride in boiling chloroform produced 1-benzoyloxy-2-phenyl-3-(2-quinolyl) indole (5) and 1-hydroxy-2-phenyl-3-(2-quinolyl) indole (6). In the reaction using tosyl chloride instead of benzoyl chloride, 6 or 2-phenyl-3-(2-quinolyl) indole (8) was formed. These results demonstrate that the enehydroxylamine systems in 1 and 1-benzoyloxy-2-phenylindole (4) can behave as nucleophilic species as a result of enamine-like polarization.

著者

吉村 英敏 山本 弘明 佐伯 清太郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.21, no.10, pp.2231-2236, 1973-10-25 (Released:2008-03-31)

被引用文献数

22 23

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In order to understand the toxic nature of Kanechlor-400 (KC-400, a commercial preparation of polychlorinated biphenyls) and establish the treatment of the patients of this KC-400 intoxication (so-called Yusho), metabolic fate of 2, 4, 3', 4'-tetrachlorobiphenyl (2, 4, 3', 4'-TCB), a major component of KC-400, was investigated using rats. It was found that at least four metabolites having phenolic nature were excreted exclusively into the feces together with a large amount of unchanged 2, 4, 3', 4'-TCB. Among these, a major metabolite (M-A2), mp 155-156°, and a minor metabolite (M-A1), mp 92-98°, were isolated from the feces and characterized to be monohydroxylated TCB by ultraviolet, infrared, nuclear magnetic resonance, and mass spectral analyses. After 2, 4, 3', 4'-TCB was orally administered at a single dose of 25 mg/body to the rat, a little less than one half of the dose was excreted as unchanged 2, 4, 3', 4'-TCB during 12 days, most of which were eliminated in the first day. The excretion of major metabolite reached maximum at the second day, and total M-A2 was accounted for about 10% of dose during 12 days. Both 2, 4, 3', 4'-TCB and its major metabolite were still excreted in a small but significant amount on 12th day.

著者

吉村 英敏 小沢 直記 佐伯 清太郎

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.4, pp.1215-1221, 1978-04-25 (Released:2008-03-31)

被引用文献数

53 65

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The inductive effect of Kanechlor 400 (KC-400), the Japanese polychlorinated biphenyl (PCB) preparation containing 48% chlorine, and several individual PCB isomers on the hepatic microsomal enzymes of rats was investigated. Pretreatment with KC-400 increased significantly the activity of microsomal aminopyrine (AM) demethylase, aniline (AN) hydroxylase and NADPH-cytochrome c reductase, and the content of cytochromes P-450 and b5 just like phenobarbital (PB)-pretreatment. However, it afforded the CO-difference spectrum revealing the peak at 448 nm same as pretreatment with 3-methylcholanthrene (MC). The inhibitory effect of SKF 525-A and 7, 8-benzoflavone on AM demethylation and AN hydroxylation, respectively, in KC-400-induced microsomes also resembled that in microsomes induced by PB plus MC. Further studies using individual PCBs indicated that these compounds were divided into two groups ; namely, 4, 4'-dichlorobiphenyl (DCB), 2, 5, 2', 5'-and 2, 4, 3', 4'-tetrachlorobiphenyl (TCB) were categorized as PB-type, whereas the other group including 3, 4, 3', 4'-TCB, 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) and 3, 4, 5, 3', 4', 5'-hexachlorobiphenyl (HCB) was categorized as MC-type inducers. Decachlorobiphenyl, the completely chlorinated biphenyl derivative, was found to belong to PB-type. These conclusions were further supported by a spectral study with hexobarbital, which induced type I spectral changes with microsomes from control and 2, 4, 3', 4'-TCB-treated rats, and caused modified type II spectral change with microsomes from 3, 4, 5, 3', 4'-PenCB-treated rats. Considering these results with individual PCBs, it can be assumed that chlorination of both of the para-(4, 4') and two of the meta-positions (3, 3' or 5, 5') of biphenyl is a minimum requirement for the structure to induce cytochrome P-448.

著者

Jie Hao Wei-Wei Li Hong Du Zhi-Fang Zhao Fan Liu Jing-Chao Lu Xiu-Chun Yang Wei Cui

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.64, no.6, pp.548-557, 2016-06-01 (Released:2016-06-01)

参考文献数

27

被引用文献数

5 31

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How to provide effective prevention and treatment of myocardial ischemia/reperfusion (I/R) injury and study of the mechanism underlying I/R injury are hotspots of current research. This study aimed to elucidate the effect and cardioprotective mechanism of vitamin C (VC) on myocardial I/R injury. Our study introduced two different I/R models: I/R in vitro and oxygen–glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes. We used the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) and the mitochondrial KATP (mitoKATP) channel inhibitor 5-hydroxydecanoate (5-HD) to analyze the underlying mechanisms. We found that post-treatment with VC decreased I/R injury in our models. Post-treatment with VC significantly decreased I/R-induced injury, attenuated apoptosis, and maintained the functional integrity of mitochondria via alleviation of Ca2+ overload, reactive oxygen species burst, inhibition of the opening of mPTP, and prevention of mitochondrial membrane potential (ΔΨm) depolarization. VC post-treatment increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. The present results demonstrate that VC might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening via activation of mitoKATP channels. VC mediates cardioprotection via activation of the phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway. These findings may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury.