WO1992017448A1 - Derive de 3-methylenisoindolin-1-one - Google Patents

Derive de 3-methylenisoindolin-1-one Download PDF

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Publication number
WO1992017448A1
WO1992017448A1 PCT/JP1992/000246 JP9200246W WO9217448A1 WO 1992017448 A1 WO1992017448 A1 WO 1992017448A1 JP 9200246 W JP9200246 W JP 9200246W WO 9217448 A1 WO9217448 A1 WO 9217448A1
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Prior art keywords
compound
dihydro
isoindole
kbr
except
Prior art date
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PCT/JP1992/000246
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English (en)
Japanese (ja)
Inventor
Shinichiro Mohri
Hiroyuki Obase
Junichi Ikeda
Kazuhiro Kubo
Akihisa Mori
Akio Ishii
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Kyowa Hakko Kogyo Co., Ltd.
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Publication of WO1992017448A1 publication Critical patent/WO1992017448A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/46—Iso-indoles; Hydrogenated iso-indoles with an oxygen atom in position 1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/58—[b]- or [c]-condensed
    • C07D209/62—Naphtho [c] pyrroles; Hydrogenated naphtho [c] pyrroles
    • C07D209/64—Naphtho [c] pyrroles; Hydrogenated naphtho [c] pyrroles with an oxygen atom in position 1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Definitions

  • the present invention relates to a 3-methyleneisoindoline-1-one derivative having a protective effect on ischemic brain damage.
  • An object of the present invention is to provide a 3-methyleneisoindoline 111-one derivative having a protective effect on ischemic brain injury.
  • the present invention provides a compound of the formula (I)
  • Y is one (CH 2 ). 1 (where n represents an integer of 1 to 4) or
  • Z is or represents a hydroxy, or R 2 and - represents an 0- CO- - turned cord one Z- R 2) represents,
  • X is a substituted or unsubstituted aryl, a substituted or unsubstituted pyridinole, imidazolyl, thiazolyl, benzimidazolyl, tetrahydroisoquinolyl, one NR 5 R 6 (in the formula,
  • R 1 And R 2 are the same or different and are hydrogen, lower alkyl, substituted or unsubstituted aryl, cyano, C0 2 R 11 wherein R 11 is hydrogen, lower alkyl, aralkyl, substituted or unsubstituted aryl or One (CH 2 ) nd NR 7 ′ R 88 (where nd represents an integer of 1 to 3, and R 7e and R 8e have the same meanings as R 7 and R 8 described above); One W— (CH 2 ) ne- NR 5e R 6 ′ (wherein, W represents a single bond, — ⁇ —, ne represents an integer of 1-3, R 5 ′ and R 5 and R synonymous with e ),
  • the substituted aryl, the aryl moiety in the substituted aralkyl, the pyridyl and the substituent of the pyrimidyl are the same or different and each have 1 to 3 substituents, for example, lower alkyl, 'trifluoromethyl, lower alkoxy, halogen, nitro, pyrrolidinyl.
  • the alkyl portion and the halogen of the lower alkyl and the lower alkoxy are as defined above.
  • R 1A and R 2A are the same or different and represent hydrogen, lower alkyl or mono (CH 2 )) in the definition of WiBR 1 and R 2 , and M represents a magnesium halide or lithium atom.
  • A, B, R 3 , R 4 , n, m and X are as defined above.
  • reaction is first compound (II) and 1 to 5 equivalents of an organometallic reagent and ( ⁇ ), for example, Te tetrahydrofuran, ether, an inert solvent such as Tozoreen, at 0 to 80 e C, 1 to 48 hours
  • organometallic reagent and ( ⁇ ) for example, Te tetrahydrofuran, ether, an inert solvent such as Tozoreen
  • the compound (IV) is dehydrated in an inert solvent such as tetrahydrofuran, ether or toluene at 0 ° C to the boiling point of the solvent for 1 to 24 hours in the presence of, for example, hydrogen chloride, hydrochloric acid, sulfuric acid, p-toluenesulfonic acid.
  • the compound ( ⁇ a) can be obtained by subjecting it to a reaction.
  • the E-isomer is preferentially generated.0
  • R 1A and R 2A are hydrogen and the other is lower alkyl in the compound (IV)
  • the dehydration reaction gives the E-form : N one (CH 2 ) n — X
  • R 'AA represents a lower alkyl in the definition of R
  • Y is — (CH 2 ) n —
  • X is a compound (lb) represented by the following definition, which can be obtained according to the following reaction steps.
  • the compound (V) for example with sodium hydride equivalents of potassium hydride, diisocyanato Riumuami presence lambda 1 to 1 0 equivalents of a compound of a base such as de (VI), Jimechiruhoru Muami de, toluene, tetrahydrofuran and the like not
  • the compound (VII) can be obtained by reacting at 0 to 50 ° C. for 1 to 24 hours in an active solvent.
  • compound (VII) and compound (VIII) are mixed in an inert solvent such as isopropyl alcohol, toluene, dimethylformamide, ethanol, etc., for example, triethylamine, sodium carbonate, carbonated sodium, sodium hydroxide, hydrogenation. 0 in the presence of a base such as sodium.
  • an inert solvent such as isopropyl alcohol, toluene, dimethylformamide, ethanol, etc.
  • triethylamine sodium carbonate, carbonated sodium, sodium hydroxide, hydrogenation.
  • a base such as sodium.
  • the compound (lb) can be obtained by reacting at a temperature of C to the boiling point of the solvent for 1 to 24 hours.
  • Hal represents halogen as defined above for Ha
  • A, B, R 1 , R
  • R 3 , R 4 , X A and n are as defined above.
  • compound () and 1 to 5 equivalents of compound (X), hydrochloric acid or hydrobromide are mixed in an inert solvent such as ethanol, isoprono, phenol, dimethylene chloride, chloroform, and tetrahydrofuran.
  • an appropriate acid such as hydrogen chloride, hydrobromic acid
  • the compound (XI) can be obtained by reacting at 0 to 50 ° C. for 1 to 12 hours.
  • compound (XI) and compound (VI II) are mixed with an inert solvent such as ethanol, isopropanol, toluene, dimethylformamide, etc., for example, triethylamine, sodium carbonate, carbonated lime, 7j sodium oxide, sodium hydride, etc.
  • an inert solvent such as ethanol, isopropanol, toluene, dimethylformamide, etc., for example, triethylamine, sodium carbonate, carbonated lime, 7j sodium oxide, sodium hydride, etc.
  • the compound (lb) can be obtained by reacting at 0 to the boiling point of the solvent for 1 to 24 hours in the presence of the following base:
  • the compound (Ic) in which Y is — (CH 2 ) n can be obtained by the following reaction step.
  • R A represents hydrogen, lower alkyl or substituted or unsubstituted aryl in the definition of R] or R 2
  • A, B, R s , R 4 , X and n are as defined above. Is
  • Compound ( ⁇ ) and compound (XIV) are combined with an inert solvent such as ethanol, isoprono, ethanol, and toluene in the presence of a base such as piperidine, pyridine, sodium hydroxide, and sodium methylate. ⁇ 200.
  • the compound (Id) can be obtained by reacting with C for 1 to 24 hours.
  • the compound (XVI) and the compound (XVI I) are mixed in an inert solvent such as ethanol, isopropanol, toluene, and dimethylformamide, for example, triethylamine, sodium carbonate, carbonated sodium carbonate, sodium hydroxide, sodium hydrogenated sodium, and the like.
  • the compound (Ie) can be obtained by reacting in the presence of a base at 0 e C to the boiling point of the solvent for 1 to 24 hours.
  • Compound (If) can be obtained from compound (XVIII) in the same manner as in Production Method 6.
  • the compound ⁇ which is a starting material, can be synthesized by a Grignard reaction with respect to ID (ID).
  • R B is in the definitions of R 1 and R 2 - C0 2 R '(wherein, R na of R 1 other than hydrogen' represents a) one C0NR Sb R 6b or a C0 H (CH 2 ) nf X ′, wherein A, B, R 3 , R 4 , X and n are as defined above.
  • the compound (Ii) in which a lactone ring is formed between Y and R 2 ′ can be obtained according to the following reaction steps.
  • Compound (XX) and compound ( ⁇ ) are converted into methanol, ethanol, isopropanol, and toluene. By reacting in an inert solvent such as 0 to the boiling point of the solvent for 1 to 12 hours, the compound ( ⁇ ) having a lactone ring can be obtained.
  • Compound (I) and compound (B) (Z-form) in which R 1 is hydrogen, including intermediates (VII) or (XI), obtained in these production methods are present in the presence of a small amount of acid such as hydrogen chloride.
  • the isomerized compound (C) (E-isomer) can be obtained by treating in an inert solvent such as black form with 0 to the boiling point of the solvent for 1 to 24 hours.
  • R ° represents R 2 other than hydrogen
  • X 0 represents X or Hal
  • A, B, R 3 , R 4 and n are as defined above.
  • a salt of compound (I) when compound (I) is obtained in the form of a salt, the compound may be purified as it is, and when compound (I) is obtained in a free form, it may be purified with a common organic solvent A salt may be formed by dissolving or suspending and adding an acid. Further, when compound (I) has a double bond geometric isomer, this mixture may be recrystallized or subjected to various chromatographic methods according to a conventional method. It can be separated and purified by chromatography and the like.
  • the present invention includes all possible isomers including these geometric stereoisomers and mixtures thereof.
  • test compound was orally or intraperitoneally administered to male ddy mice weighing 20 to 22 g.
  • the mouse was decapitated 1 hour after the drug administration for oral administration and 30 minutes after intraperitoneal administration, and the time until gasping of the cut off head was stopped after the decapitation was measured.
  • Sa is the phosphate of the compound,
  • Sa2 is the chemical
  • the compound represents methanesulfonic acid. Test example 3.
  • Test Example 4 A test compound was orally (po) or intraperitoneally (ip) administered to a dd mouse weighing 20 to 25 g. MLD (minimum lethal dose) was determined by measuring the mortality 7 days after administration. Table 5 shows the results. Table 5
  • Pharmaceutical carriers to be used include, for example, 7j, distilled water for injection, physiological saline, glucose, fructose, sucrose, mannitol, lactose, starch, cellulose, methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, alginic acid, Examples include talc, sodium citrate, calcium carbonate, calcium hydrogen phosphate, magnesium stearate, urea, silicone resin, sorbitan fatty acid ester, and glycerin fatty acid ester.
  • a phosphate salt of compound 17 was obtained according to the method of Example 3 except that 1- (4-fluorophenyl) pidazine was changed to getylamine.
  • a phosphate salt of Compound 23 was obtained according to the method of Example 3 except that 4-phenylbiperidine was used instead of 1- (4-fluorophenyl) pidazine.
  • a hydrochloride of Compound 25 was obtained according to the method of Example 3 except that 4-hydroxy-4-phenylbiperidine was used instead of 1- (4-fluorophenyl) pirazine.
  • the hydrochloride of compound 26 was obtained according to the method of Example 3 except that 4-hydroxy-41- (3-trifluoromethylphenyl) piperidine was used instead of 1- (4-fluorophenyl) piperazine. Was.
  • the hydrochloride salt of compound 27 was obtained according to the method of Example 3 except that 1- (2-methoxyphenyl) piperazine was used instead of 1- (4-fluorophenyl) piperazine.
  • the hydrochloride salt of compound 31 was obtained according to the method of Example 3 except for using 11- (pyrimidine-1-yl) pirazine instead of 11- (4-fluorophenyl) piperazine.
  • a hydrochloride of compound 33 was obtained according to the method of Example 3 except that 1-phenylbiperazine was used instead of 1- (4-fluorophenyl) piperazine.
  • the hydrochloride salt of Compound 34 was obtained according to the method of Example 3 except that 1- (2-fluorophenyl) piperazine was used instead of 1- (4-fluorophenyl) pirazine.
  • a hydrochloride of compound 35 was obtained according to the method of Example 3 except that 1- (4-chlorophenyl) pirazine was used instead of 1- (4-fluorophenyl) pirazine.
  • IR (KBr) Li (cm " 1 ); 3600-3200, 2955, 2320, 1690, 1680, 1650, 1495, 1415, 1340
  • the hydrochloride salt of compound 37 was obtained according to the method of Example 3 except that 11- (pyridine-2-yl) pirazine was used instead of 11- (4-fluorophenyl) pirazine.
  • IR (KBr) >> ax (cm " 1 ); 3600-1 3200, 2960, 1685, 1645, 1615, 1420, 1340 2.0 -2.2C2H, ra), 3.0 -3.3C2H, m), 3.3-3.5 (1H, m), 3.5-3.75 (4H, m), 3.75-3.9 (2H, m), 4.4-4.6 (2H, in ), 5.62 (1H, d, J 9.5Hz), 6.9-1 7.0 (1H, m), 7.25-7.35 (1H, ID), 7.5-8.05 (5H, m), 8.05 -8.15 (1H, ra)
  • a hydrochloride of compound 39 was obtained according to the method of Example 3 except that 11- (3-trifluoromethylphenyl) pirazine was used instead of 11- (4-fluorophenyl) pirazine.
  • the hydrochloride salt of compound 40 was obtained according to the method of Example 3 except that 1- (3-fluorophenyl) piperazine was used instead of 1- (4-fluorophenyl) pirazine.
  • the hydrochloride salt of compound 41 was obtained according to the method of Example 3 except that 1- (2-ethoxyphenyl) piperazine was used instead of 1- (4-fluorophenyl) pirazine.
  • a hydrochloride of compound 42 was obtained according to the method of Example 3 except that 1- (4-nitrophenyl) piperazine was used instead of 1- (4-fluorophenyl) piperazine.
  • a hydrochloride of compound 43 was obtained according to the method of Example 3 except that benzimidazole was used instead of 11- (4-fluorophenyl) pidazine. Melting point: 82 ° C (ethanol)
  • a hydrochloride of compound 44 was obtained according to the method of Example 3 except that 11-morpholinocarboxymethylpiperazine was used instead of 11- (4-fluorophenyl) piperazine.
  • Example 3 According to the method of Example 3, except that 1- (2,6-dipyrrolidinylpyrimidine-141-yl) pidazine is used instead of 1- (4-fluorophenyl) pidazine, the hydrochloric acid of compound 45 is used. Salt was obtained. Melting point: 121-122 ° C (isopropanol)
  • the hydrochloride salt of compound 46 was obtained according to the method of Example 3 except that 1- (3-methoxyphenyl) pidazine was used instead of 1- (4-fluorophenyl) pidazine.
  • the hydrochloride salt of compound 47 was obtained according to the method of Example 3 except that 1-1 (4-methoxyphenyl) piperazine was used instead of I- (4-fluorophenyl) piperazine.
  • a hydrochloride of compound 68 was obtained according to the method of Example 3 except that 4-phenylbiperidine was used.
  • Compound 72 A phosphate of compound 72 was obtained according to the method of Example 4, except that compound c and getylamine obtained in Reference Example 3 were used instead of 11- (2-methoxyphenyl) pidazine. Melting point: 118-119 ° C (ethanol)
  • a phosphate salt of Compound 73 was obtained according to the method of Example 4 except that pyrrolidine was used instead of 1- (2-methoxyphenyl) pirazine.
  • the hydrochloride of compound 77 was obtained according to the method of Example 4, except that compound c and morpholine obtained in Reference Example 3 were used instead of compounds a and 11- (2-methoxyphenyl) pidazine.
  • a phosphate salt of Compound 80 was obtained according to the method of Example 4 except that 1-benzylpiperazine was used instead of 1- (2-methoxyphenyl) pidazine.
  • a phosphate salt of compound 82 was obtained according to the method of Example 4 except that compound c obtained in Reference Example 3 was used instead of compound a.
  • a hydrochloride salt of compound 83 was obtained according to the same method as that of Example 5 except that 4- [4- (2-methoxyphenyl) piperazinyl] butylamine was used instead of N, N-dimethylaminopropylamido. .
  • a phosphate of compound 84 was obtained according to the method of Example 4 except that 1- (4-fluorophenyl) pirazine was used instead of .1- (2-methoxyphenyl) pirazine.
  • a hydrochloride of Compound 87 was obtained according to the method of Example 4 except that 1-cinnamoylpiperazine was used instead of 1- (2-methoxyphenyl) pirazine.
  • a hydrochloride of Compound 92 was obtained in the same manner as in Example 5, except that 3-aminomethylpyridine was used instead of pyramine, N, N-dimethylaminobutamate.
  • a hydrochloride salt of compound 93 was obtained according to the method of Example 4 except that 1-1 (3-methoxyphenyl) piperazine was used instead of 1-1 (2-methoxyphenyl) piperazine.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Dérivé de 3-méthylèneisoindolin-1-one répondant à la formule générale (I), et sel pharmaceutiquement acceptable dudit dérivé, utiles comme médicaments grâce à leur activité de protection contre les troubles cérébraux ischémiques. Dans la formule (I), A et B peuvent être identiques ou différents et représentent chacun -CH= ou -N=; Y représente -(CH2)n- (où n représente un nombre entier pouvant aller de 1 à 4), etc.; X représente un groupe hétérocyclique substitué ou non, etc.; R1 et R2 peuvent être identiques ou différents et représentent chacun alkyle, etc.; et R3 et R4 peuvent être identiques ou différents et représentent chacun halogène, alcoxy, etc.
PCT/JP1992/000246 1991-04-01 1992-03-02 Derive de 3-methylenisoindolin-1-one WO1992017448A1 (fr)

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JP6837991 1991-04-01

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Cited By (5)

* Cited by examiner, † Cited by third party
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US7968570B2 (en) 2004-08-13 2011-06-28 Astrazeneca Ab Isoindolone compounds and their use as metabotropic glutamate receptor potentiators
US8148372B2 (en) 2008-06-06 2012-04-03 Astrazeneca Ab Metabotropic glutamate receptor isoxazole ligands and their use as potentiators—286
US8153638B2 (en) 2005-08-12 2012-04-10 Astrazeneca Ab Metabotropic glutamate-receptor-potentiating isoindolones
US8377939B2 (en) 2007-06-07 2013-02-19 Astrazeneca Ab Oxadiazole derivatives and their use as metabotropic glutamate receptor potentiators 842
CN110698445A (zh) * 2018-07-09 2020-01-17 四川大学 一类3-胺烷基苯酞类化合物、其制备方法和用途

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US8153638B2 (en) 2005-08-12 2012-04-10 Astrazeneca Ab Metabotropic glutamate-receptor-potentiating isoindolones
US8377939B2 (en) 2007-06-07 2013-02-19 Astrazeneca Ab Oxadiazole derivatives and their use as metabotropic glutamate receptor potentiators 842
US8377940B2 (en) 2007-06-07 2013-02-19 Astrazeneca Ab Oxadiazole derivatives and their use as metabotropic glutamate receptor potentiators—842
US8148372B2 (en) 2008-06-06 2012-04-03 Astrazeneca Ab Metabotropic glutamate receptor isoxazole ligands and their use as potentiators—286
CN110698445A (zh) * 2018-07-09 2020-01-17 四川大学 一类3-胺烷基苯酞类化合物、其制备方法和用途
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