UA79804C2 - Cck-1 receptor modulators - Google Patents

Info

Publication number

UA79804C2

UA79804C2 UAA200500955A UA2005000955A UA79804C2 UA 79804 C2 UA79804 C2 UA 79804C2 UA A200500955 A UAA200500955 A UA A200500955A UA 2005000955 A UA2005000955 A UA 2005000955A UA 79804 C2 UA79804 C2 UA 79804C2

Authority

UA

Ukraine

Prior art keywords

phenyl

methyl

methoxy

dichloro

necessary

Prior art date

2002-07-03

Links

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• Global Dossier
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• -1 -Ophenyl Chemical group 0.000 claims description 767
• 238000000034 method Methods 0.000 claims description 351
• 150000001875 compounds Chemical class 0.000 claims description 315
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 172
• 239000000203 mixture Substances 0.000 claims description 162
• 229910052799 carbon Inorganic materials 0.000 claims description 126
• 150000001721 carbon Chemical group 0.000 claims description 89
• 150000003839 salts Chemical class 0.000 claims description 89
• 230000015572 biosynthetic process Effects 0.000 claims description 85
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 85
• 125000000217 alkyl group Chemical group 0.000 claims description 78
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 74
• 125000005605 benzo group Chemical group 0.000 claims description 62
• 125000001424 substituent group Chemical group 0.000 claims description 58
• 229910052757 nitrogen Inorganic materials 0.000 claims description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims description 48
• 150000001408 amides Chemical class 0.000 claims description 44
• 125000004432 carbon atom Chemical group C* 0.000 claims description 42
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 41
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 40
• 150000002148 esters Chemical class 0.000 claims description 37
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
• 125000004076 pyridyl group Chemical group 0.000 claims description 30
• 125000005843 halogen group Chemical group 0.000 claims description 29
• 229920006395 saturated elastomer Polymers 0.000 claims description 29
• 125000002950 monocyclic group Chemical group 0.000 claims description 28
• 125000001624 naphthyl group Chemical group 0.000 claims description 27
• 125000006413 ring segment Chemical group 0.000 claims description 27
• 125000003118 aryl group Chemical group 0.000 claims description 26
• 239000004215 Carbon black (E152) Substances 0.000 claims description 24
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 24
• 125000004429 atom Chemical group 0.000 claims description 24
• 229930195733 hydrocarbon Natural products 0.000 claims description 24
• 150000002430 hydrocarbons Chemical class 0.000 claims description 24
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 21
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 21
• 239000001257 hydrogen Substances 0.000 claims description 16
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
• 125000005842 heteroatom Chemical group 0.000 claims description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 12
• 125000002541 furyl group Chemical group 0.000 claims description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
• 125000001544 thienyl group Chemical group 0.000 claims description 12
• KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims description 11
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 11
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 10
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
• 208000035475 disorder Diseases 0.000 claims description 10
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 10
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 9
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 9
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 9
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 9
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims description 9
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 9
• 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 9
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 9
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 9
• SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 claims description 9
• 125000002393 azetidinyl group Chemical group 0.000 claims description 9
• 239000003795 chemical substances by application Substances 0.000 claims description 9
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
• 125000002883 imidazolyl group Chemical group 0.000 claims description 9
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 9
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 9
• 125000002971 oxazolyl group Chemical group 0.000 claims description 9
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 9
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 9
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
• 125000000335 thiazolyl group Chemical group 0.000 claims description 9
• 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 9
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
• 101100061515 Caenorhabditis elegans csk-1 gene Proteins 0.000 claims description 7
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
• 239000002464 receptor antagonist Substances 0.000 claims description 7
• 229940044551 receptor antagonist Drugs 0.000 claims description 7
• 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 6
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 6
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 6
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 6
• 241000124008 Mammalia Species 0.000 claims description 6
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 5
• 244000028419 Styrax benzoin Species 0.000 claims description 5
• 235000000126 Styrax benzoin Nutrition 0.000 claims description 5
• 235000008411 Sumatra benzointree Nutrition 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 235000019382 gum benzoic Nutrition 0.000 claims description 5
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 238000005304 joining Methods 0.000 claims description 4
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
• 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims description 3
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• 208000019901 Anxiety disease Diseases 0.000 claims description 3
• 230000036506 anxiety Effects 0.000 claims description 3
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 3
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
• 125000001041 indolyl group Chemical group 0.000 claims description 3
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
• 230000008855 peristalsis Effects 0.000 claims description 3
• 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 3
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 3
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
• 206010004663 Biliary colic Diseases 0.000 claims description 2
• 206010028980 Neoplasm Diseases 0.000 claims description 2
• 208000002193 Pain Diseases 0.000 claims description 2
• 208000016222 Pancreatic disease Diseases 0.000 claims description 2
• 206010033664 Panic attack Diseases 0.000 claims description 2
• 229910052770 Uranium Inorganic materials 0.000 claims description 2
• 208000022531 anorexia Diseases 0.000 claims description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 201000011510 cancer Diseases 0.000 claims description 2
• 206010061428 decreased appetite Diseases 0.000 claims description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
• 206010013663 drug dependence Diseases 0.000 claims description 2
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 230000036407 pain Effects 0.000 claims description 2
• 208000024691 pancreas disease Diseases 0.000 claims description 2
• 208000019906 panic disease Diseases 0.000 claims description 2
• 201000000980 schizophrenia Diseases 0.000 claims description 2
• 230000003248 secreting effect Effects 0.000 claims description 2
• 208000011117 substance-related disease Diseases 0.000 claims description 2
• 125000001931 aliphatic group Chemical group 0.000 claims 20
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 8
• IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims 2
• OLVMPQNPFWQNTC-UHFFFAOYSA-N 2-hydroxy-2-phenyl-1-(2-phenylphenyl)ethanone Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1C1=CC=CC=C1 OLVMPQNPFWQNTC-UHFFFAOYSA-N 0.000 claims 1
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 claims 1
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
• APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims 1
• 238000012876 topography Methods 0.000 claims 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 abstract description 29
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 256
• 238000004128 high performance liquid chromatography Methods 0.000 description 176
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 138
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 134
• 150000003217 pyrazoles Chemical class 0.000 description 130
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 111
• 102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 107
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 100
• 239000000243 solution Substances 0.000 description 100
• 239000000047 product Substances 0.000 description 91
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 79
• 239000002904 solvent Substances 0.000 description 76
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
• 239000002253 acid Substances 0.000 description 68
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 64
• 239000011541 reaction mixture Substances 0.000 description 61
• 238000007792 addition Methods 0.000 description 52
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
• 238000003776 cleavage reaction Methods 0.000 description 48
• 238000005755 formation reaction Methods 0.000 description 48
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 47
• 238000002425 crystallisation Methods 0.000 description 47
• 230000008025 crystallization Effects 0.000 description 46
• 238000009833 condensation Methods 0.000 description 45
• 230000005494 condensation Effects 0.000 description 45
• 230000007017 scission Effects 0.000 description 43
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
• 238000006243 chemical reaction Methods 0.000 description 42
• 235000019439 ethyl acetate Nutrition 0.000 description 41
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
• 150000002429 hydrazines Chemical class 0.000 description 36
• 239000012044 organic layer Substances 0.000 description 34
• 239000010410 layer Substances 0.000 description 33
• JYRIJBPELVXSTC-UHFFFAOYSA-N cycloprop-2-yn-1-one Chemical compound O=C1C#C1 JYRIJBPELVXSTC-UHFFFAOYSA-N 0.000 description 32
• 235000019441 ethanol Nutrition 0.000 description 30
• 238000006467 substitution reaction Methods 0.000 description 30
• 230000007062 hydrolysis Effects 0.000 description 28
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• 210000004027 cell Anatomy 0.000 description 26
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• 230000008569 process Effects 0.000 description 26
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
• 239000000741 silica gel Substances 0.000 description 25
• 229910002027 silica gel Inorganic materials 0.000 description 25
• KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical class OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 24
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 24
• 239000012429 reaction media Substances 0.000 description 23
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
• 238000010791 quenching Methods 0.000 description 22
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• 239000012458 free base Substances 0.000 description 21
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 20
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• 239000003960 organic solvent Substances 0.000 description 16
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• 238000001308 synthesis method Methods 0.000 description 11
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