RU2298002C2 - Производные хинолина в качестве антагонистов npy - Google Patents

Info

Publication number

RU2298002C2

RU2298002C2 RU2004126936/04A RU2004126936A RU2298002C2 RU 2298002 C2 RU2298002 C2 RU 2298002C2 RU 2004126936/04 A RU2004126936/04 A RU 2004126936/04A RU 2004126936 A RU2004126936 A RU 2004126936A RU 2298002 C2 RU2298002 C2 RU 2298002C2

Authority

RU

Russia

Prior art keywords

methyl

pyrrolidin

ylquinolin

methylquinolin

alkyl

Prior art date

2002-02-04

Links

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• Global Dossier
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• 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title claims abstract description 9
• 239000005557 antagonist Substances 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 145
• -1 benzylcarbonyl Chemical group 0.000 claims abstract description 134
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 66
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 31
• 238000000034 method Methods 0.000 claims abstract description 28
• 238000011282 treatment Methods 0.000 claims abstract description 25
• 208000008589 Obesity Diseases 0.000 claims abstract description 20
• 235000020824 obesity Nutrition 0.000 claims abstract description 20
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 18
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 14
• 239000003814 drug Substances 0.000 claims abstract description 14
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 14
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 14
• 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 13
• 208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 13
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 13
• 206010003246 arthritis Diseases 0.000 claims abstract description 13
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims abstract description 13
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 13
• 201000006370 kidney failure Diseases 0.000 claims abstract description 13
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 10
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 10
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 9
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
• 125000003725 azepanyl group Chemical group 0.000 claims abstract description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 7
• 125000002541 furyl group Chemical group 0.000 claims abstract description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
• 125000001544 thienyl group Chemical group 0.000 claims abstract description 6
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims abstract description 5
• 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 4
• 238000006243 chemical reaction Methods 0.000 claims description 153
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 45
• 150000003839 salts Chemical class 0.000 claims description 27
• 229910052739 hydrogen Inorganic materials 0.000 claims description 25
• 239000001257 hydrogen Substances 0.000 claims description 25
• 229940086609 Lipase inhibitor Drugs 0.000 claims description 20
• 150000002148 esters Chemical class 0.000 claims description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• 125000001424 substituent group Chemical group 0.000 claims description 18
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical group CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 16
• 238000004519 manufacturing process Methods 0.000 claims description 15
• 229960001243 orlistat Drugs 0.000 claims description 15
• 230000002265 prevention Effects 0.000 claims description 15
• 239000000460 chlorine Substances 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 150000002367 halogens Chemical group 0.000 claims description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
• 101710151321 Melanostatin Proteins 0.000 claims description 12
• 102400000064 Neuropeptide Y Human genes 0.000 claims description 12
• 208000030814 Eating disease Diseases 0.000 claims description 10
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 10
• 235000014632 disordered eating Nutrition 0.000 claims description 10
• 229910052740 iodine Inorganic materials 0.000 claims description 9
• CTOKVDGFJMEMLN-UHFFFAOYSA-N [1-(7-amino-2-methylquinolin-4-yl)pyrrolidin-2-yl]methanol Chemical compound C=12C=CC(N)=CC2=NC(C)=CC=1N1CCCC1CO CTOKVDGFJMEMLN-UHFFFAOYSA-N 0.000 claims description 8
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 7
• 229940079593 drug Drugs 0.000 claims description 7
• 150000002431 hydrogen Chemical class 0.000 claims description 7
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
• 229910052794 bromium Inorganic materials 0.000 claims description 6
• 229910052801 chlorine Inorganic materials 0.000 claims description 6
• FLCRSCHUKYNXKW-UHFFFAOYSA-N 4-(3-ethoxypyrrolidin-1-yl)-2-methylquinolin-7-amine Chemical compound C1C(OCC)CCN1C1=CC(C)=NC2=CC(N)=CC=C12 FLCRSCHUKYNXKW-UHFFFAOYSA-N 0.000 claims description 5
• 239000013543 active substance Substances 0.000 claims description 5
• 201000010099 disease Diseases 0.000 claims description 5
• 102000005962 receptors Human genes 0.000 claims description 5
• 108020003175 receptors Proteins 0.000 claims description 5
• YIAYAZXGXKSBRM-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)amino]benzonitrile Chemical compound C=12C=CC(NC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 YIAYAZXGXKSBRM-UHFFFAOYSA-N 0.000 claims description 4
• MVJVQMRGBDNHOW-SFHVURJKSA-N 4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methyl-n-pyridin-3-ylquinolin-7-amine Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(NC=3C=NC=CC=3)=CC=C12 MVJVQMRGBDNHOW-SFHVURJKSA-N 0.000 claims description 4
• HAYLQPXSZLDLQK-KRWDZBQOSA-N 4-[(3s)-3-methoxypyrrolidin-1-yl]-2-methyl-n-pyridin-3-ylquinolin-7-amine Chemical compound C1[C@@H](OC)CCN1C1=CC(C)=NC2=CC(NC=3C=NC=CC=3)=CC=C12 HAYLQPXSZLDLQK-KRWDZBQOSA-N 0.000 claims description 4
• VDQKHTJHDWFTLL-FQEVSTJZSA-N 4-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]amino]benzonitrile Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(NC=3C=CC(=CC=3)C#N)=CC=C12 VDQKHTJHDWFTLL-FQEVSTJZSA-N 0.000 claims description 4
• UWDNSCIPWKCXII-UHFFFAOYSA-N CC1=NC2=CC(=C(C=C2C(=C1)N1CCCC1)C)C1=C(OC=C1)C(=O)N Chemical compound CC1=NC2=CC(=C(C=C2C(=C1)N1CCCC1)C)C1=C(OC=C1)C(=O)N UWDNSCIPWKCXII-UHFFFAOYSA-N 0.000 claims description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
• 108050002826 Neuropeptide Y Receptor Proteins 0.000 claims description 4
• 102000012301 Neuropeptide Y receptor Human genes 0.000 claims description 4
• 239000011630 iodine Substances 0.000 claims description 4
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
• HUACSPMJAPGPNA-UHFFFAOYSA-N n-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanesulfonamide Chemical compound C=12C=CC(NS(C)(=O)=O)=CC2=NC(C)=CC=1N1CCCC1 HUACSPMJAPGPNA-UHFFFAOYSA-N 0.000 claims description 4
• UPTVWHNDQOIPGI-UHFFFAOYSA-N n-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)pyridine-3-carboxamide Chemical compound C=12C=CC(NC(=O)C=3C=NC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 UPTVWHNDQOIPGI-UHFFFAOYSA-N 0.000 claims description 4
• PMJPHEAEMAOVPH-UHFFFAOYSA-N n-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)pyridine-4-carboxamide Chemical compound C=12C=CC(NC(=O)C=3C=CN=CC=3)=CC2=NC(C)=CC=1N1CCCC1 PMJPHEAEMAOVPH-UHFFFAOYSA-N 0.000 claims description 4
• QYBCQTIWTCSCPL-HNNXBMFYSA-N n-[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]propanamide Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(NC(=O)CC)=CC=C12 QYBCQTIWTCSCPL-HNNXBMFYSA-N 0.000 claims description 4
• BLIFSQROOJKZEL-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-n-(thiophen-2-ylmethyl)quinolin-7-amine Chemical compound C=12C=CC(NCC=3SC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 BLIFSQROOJKZEL-UHFFFAOYSA-N 0.000 claims description 3
• APPRTOYEZDOHKS-UHFFFAOYSA-N 4-[2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-amine Chemical compound COCC1CCCN1C1=CC(C)=NC2=CC(N)=CC=C12 APPRTOYEZDOHKS-UHFFFAOYSA-N 0.000 claims description 3
• SRNUHYAZNVNSKZ-HXUWFJFHSA-N 4-[[4-[(2r)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]amino]benzonitrile Chemical compound COC[C@H]1CCCN1C1=CC(C)=NC2=CC(NC=3C=CC(=CC=3)C#N)=CC=C12 SRNUHYAZNVNSKZ-HXUWFJFHSA-N 0.000 claims description 3
• YAVPLAQEQDEVLN-IBGZPJMESA-N 4-[[4-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]amino]benzonitrile Chemical compound C=12C=CC(NC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCC[C@H]1CO YAVPLAQEQDEVLN-IBGZPJMESA-N 0.000 claims description 3
• CLTYJMAMVSIRCT-UHFFFAOYSA-N 4-cyano-n-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)benzamide Chemical compound C=12C=CC(NC(=O)C=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 CLTYJMAMVSIRCT-UHFFFAOYSA-N 0.000 claims description 3
• SNFQXWHVDARKDG-UHFFFAOYSA-N CC1=NC2=CC(=CC=C2C(=C1)N1CCCC1)C1=NC=CC=C1S(=O)(=O)N Chemical compound CC1=NC2=CC(=CC=C2C(=C1)N1CCCC1)C1=NC=CC=C1S(=O)(=O)N SNFQXWHVDARKDG-UHFFFAOYSA-N 0.000 claims description 3
• 102100029549 Neuropeptide Y receptor type 5 Human genes 0.000 claims description 3
• 101710198055 Neuropeptide Y receptor type 5 Proteins 0.000 claims description 3
• 239000002253 acid Substances 0.000 claims description 3
• 125000006307 alkoxy benzyl group Chemical group 0.000 claims description 3
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
• WDHFAKVAPOJMFZ-UHFFFAOYSA-N n-(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)propanamide Chemical compound C=12C=C(C)C(NC(=O)CC)=CC2=NC(C)=CC=1N1CCCC1 WDHFAKVAPOJMFZ-UHFFFAOYSA-N 0.000 claims description 3
• CGXHQPCFJBXZHQ-KRWDZBQOSA-N n-[4-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]pyridine-3-carboxamide Chemical compound C=12C=CC(NC(=O)C=3C=NC=CC=3)=CC2=NC(C)=CC=1N1CCC[C@H]1CO CGXHQPCFJBXZHQ-KRWDZBQOSA-N 0.000 claims description 3
• DRZKMEMZVIYCJK-UHFFFAOYSA-N 4-fluoro-n-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)benzamide Chemical compound C=12C=CC(NC(=O)C=3C=CC(F)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 DRZKMEMZVIYCJK-UHFFFAOYSA-N 0.000 claims description 2
• 108090000189 Neuropeptides Proteins 0.000 claims description 2
• 150000003248 quinolines Chemical class 0.000 claims description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 3
• 230000003042 antagnostic effect Effects 0.000 claims 2
• 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims 2
• 239000000126 substance Substances 0.000 abstract description 4
• 230000015572 biosynthetic process Effects 0.000 abstract description 3
• 235000013305 food Nutrition 0.000 abstract description 3
• 238000011321 prophylaxis Methods 0.000 abstract description 3
• 238000003786 synthesis reaction Methods 0.000 abstract description 3
• 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 abstract description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 3
• 125000004429 atom Chemical group 0.000 abstract 1
• 208000035475 disorder Diseases 0.000 abstract 1
• 230000000694 effects Effects 0.000 abstract 1
• 125000005843 halogen group Chemical group 0.000 abstract 1
• 230000007721 medicinal effect Effects 0.000 abstract 1
• 238000001819 mass spectrum Methods 0.000 description 130
• 239000007787 solid Substances 0.000 description 110
• WUKXTJQCEGKRDX-UHFFFAOYSA-N 7-iodo-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(I)=CC2=NC(C)=CC=1N1CCCC1 WUKXTJQCEGKRDX-UHFFFAOYSA-N 0.000 description 61
• 239000000047 product Substances 0.000 description 47
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 32
• 150000001412 amines Chemical class 0.000 description 26
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
• 239000002904 solvent Substances 0.000 description 18
• 239000000203 mixture Substances 0.000 description 17
• 239000003921 oil Substances 0.000 description 17
• 235000019198 oils Nutrition 0.000 description 17
• CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 16
• 239000006260 foam Substances 0.000 description 16
• 239000000463 material Substances 0.000 description 16
• 239000000243 solution Substances 0.000 description 15
• FHFZHPWRKFOURN-ZOWNYOTGSA-N 4-[(3s)-3-ethoxypyrrolidin-1-yl]-7-iodo-2-methylquinoline;hydrochloride Chemical compound Cl.C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(I)=CC=C12 FHFZHPWRKFOURN-ZOWNYOTGSA-N 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• KROCOLWZJDTCPV-LBPRGKRZSA-N [(2s)-1-(7-iodo-2-methylquinolin-4-yl)pyrrolidin-2-yl]methanol Chemical compound C=12C=CC(I)=CC2=NC(C)=CC=1N1CCC[C@H]1CO KROCOLWZJDTCPV-LBPRGKRZSA-N 0.000 description 13
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
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• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
• 125000003118 aryl group Chemical group 0.000 description 12
• 239000002775 capsule Substances 0.000 description 11
• LLBYZZCOVUGZSS-UHFFFAOYSA-N 4-chloro-7-iodo-2-methylquinoline Chemical compound C1=CC(I)=CC2=NC(C)=CC(Cl)=C21 LLBYZZCOVUGZSS-UHFFFAOYSA-N 0.000 description 10
• OBPXIDLWMCPPTF-ZDUSSCGKSA-N 7-iodo-4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinoline Chemical compound COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(I)=CC=C12 OBPXIDLWMCPPTF-ZDUSSCGKSA-N 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 125000001309 chloro group Chemical group Cl* 0.000 description 10
• 239000012458 free base Substances 0.000 description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
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• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
• URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
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• 239000001828 Gelatine Substances 0.000 description 7
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• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 7
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• 239000000741 silica gel Substances 0.000 description 7
• 229910002027 silica gel Inorganic materials 0.000 description 7
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
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