AU2005316972B2 - Chromanylurea compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor and uses thereof - Google Patents

Info

Publication number

AU2005316972B2

AU2005316972B2 AU2005316972A AU2005316972A AU2005316972B2 AU 2005316972 B2 AU2005316972 B2 AU 2005316972B2 AU 2005316972 A AU2005316972 A AU 2005316972A AU 2005316972 A AU2005316972 A AU 2005316972A AU 2005316972 B2 AU2005316972 B2 AU 2005316972B2

Authority

AU

Australia

Prior art keywords

alkyl

indazol

dihydro

chromen

methyl

Prior art date

2004-11-24

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Ceased

Links

• Espacenet
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 318
• 108010025083 TRPV1 receptor Proteins 0.000 title abstract description 20
• 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 title description 14
• 102000005962 receptors Human genes 0.000 title description 7
• 150000003839 salts Chemical class 0.000 claims abstract description 8
• 230000001668 ameliorated effect Effects 0.000 claims abstract description 4
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 228
• 238000000034 method Methods 0.000 claims description 128
• -1 2,3-dihydroindolyl Chemical group 0.000 claims description 123
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 69
• 229910052739 hydrogen Inorganic materials 0.000 claims description 63
• 239000001257 hydrogen Substances 0.000 claims description 59
• 239000004202 carbamide Substances 0.000 claims description 55
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
• 125000001188 haloalkyl group Chemical group 0.000 claims description 45
• 125000003342 alkenyl group Chemical group 0.000 claims description 33
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 29
• 125000001072 heteroaryl group Chemical group 0.000 claims description 28
• 125000001424 substituent group Chemical group 0.000 claims description 28
• 125000003118 aryl group Chemical group 0.000 claims description 27
• 125000003545 alkoxy group Chemical group 0.000 claims description 23
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 21
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
• 125000002950 monocyclic group Chemical group 0.000 claims description 20
• 238000011282 treatment Methods 0.000 claims description 20
• 229910052736 halogen Inorganic materials 0.000 claims description 19
• 150000002367 halogens Chemical group 0.000 claims description 19
• 208000002193 Pain Diseases 0.000 claims description 18
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
• 208000035475 disorder Diseases 0.000 claims description 17
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 16
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 16
• 229910052705 radium Inorganic materials 0.000 claims description 16
• 125000000623 heterocyclic group Chemical group 0.000 claims description 15
• 229910052702 rhenium Inorganic materials 0.000 claims description 15
• 125000002619 bicyclic group Chemical group 0.000 claims description 12
• DIDJZJDDXQPTLN-UHFFFAOYSA-N indazole-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)N=CC2=C1 DIDJZJDDXQPTLN-UHFFFAOYSA-N 0.000 claims description 11
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
• 230000036407 pain Effects 0.000 claims description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 9
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 8
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
• 108010062740 TRPV Cation Channels Proteins 0.000 claims description 6
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
• FGVFFUSBPJFGCF-UHFFFAOYSA-N 1-(8-tert-butyl-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1COC=2C(C(C)(C)C)=CC=CC=2C1NC(=O)NC1=CC=CC2=C1C=NN2 FGVFFUSBPJFGCF-UHFFFAOYSA-N 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 5
• 230000002485 urinary effect Effects 0.000 claims description 5
• 206010058019 Cancer Pain Diseases 0.000 claims description 4
• 208000000094 Chronic Pain Diseases 0.000 claims description 4
• 206010065390 Inflammatory pain Diseases 0.000 claims description 4
• 208000008930 Low Back Pain Diseases 0.000 claims description 4
• 206010037211 Psychomotor hyperactivity Diseases 0.000 claims description 4
• 206010046543 Urinary incontinence Diseases 0.000 claims description 4
• 208000005298 acute pain Diseases 0.000 claims description 4
• 230000003349 osteoarthritic effect Effects 0.000 claims description 4
• 125000004043 oxo group Chemical group O=* 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• DWCDXFFPOOYDNU-UHFFFAOYSA-N 1-(2-tert-butyl-7-fluoro-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C12=CC=C(F)C=C2OC(C(C)(C)C)CC1NC(=O)NC1=CC=CC2=C1C=NN2 DWCDXFFPOOYDNU-UHFFFAOYSA-N 0.000 claims description 3
• OMIRFNXDMYBLLF-UHFFFAOYSA-N 1-(7-tert-butyl-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1COC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 OMIRFNXDMYBLLF-UHFFFAOYSA-N 0.000 claims description 3
• MASAFVZAJXRZCN-UHFFFAOYSA-N 1-(7-tert-butyl-3,4-dihydro-2h-chromen-4-yl)-3-(3-methylisoquinolin-5-yl)urea Chemical compound C1COC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=C2C=C(C)N=CC2=CC=C1 MASAFVZAJXRZCN-UHFFFAOYSA-N 0.000 claims description 3
• NVMRZBHUMZFLEI-UHFFFAOYSA-N 1-(8-cyclohexyl-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=C2)CCOC1=C2C1CCCCC1 NVMRZBHUMZFLEI-UHFFFAOYSA-N 0.000 claims description 3
• 102000011040 TRPV Cation Channels Human genes 0.000 claims description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 3
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 3
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 3
• CVNOORHKMWKCEI-UHFFFAOYSA-N 1-(1-benzyl-3,4-dihydro-2h-quinolin-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=CC=C11)CCN1CC1=CC=CC=C1 CVNOORHKMWKCEI-UHFFFAOYSA-N 0.000 claims description 2
• LNCRGVMWIDSWDZ-UHFFFAOYSA-N 1-(1-benzyl-6-tert-butyl-3,4-dihydro-2h-quinolin-3-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1C(NC(=O)NC=2C=3C=NNC=3C=CC=2)CC2=CC(C(C)(C)C)=CC=C2N1CC1=CC=CC=C1 LNCRGVMWIDSWDZ-UHFFFAOYSA-N 0.000 claims description 2
• UMVFAVGJJHKXRM-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-2-ylmethyl)-3-(1h-indazol-4-yl)urea Chemical compound C1C2=CC=CC=C2OC1CNC(=O)NC1=CC=CC2=C1C=NN2 UMVFAVGJJHKXRM-UHFFFAOYSA-N 0.000 claims description 2
• MJMAJBXEOLLLDS-UHFFFAOYSA-N 1-(6-chloro-7-methyl-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-5-ylurea Chemical compound C1=CC=C2C(NC(=O)NC3CCOC=4C=C(C(=CC=43)Cl)C)=CC=CC2=N1 MJMAJBXEOLLLDS-UHFFFAOYSA-N 0.000 claims description 2
• QWWCSSSULKYTLF-UHFFFAOYSA-N 1-(6-fluoro-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-5-ylurea Chemical compound C1=CC=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)F)=CC=CC2=N1 QWWCSSSULKYTLF-UHFFFAOYSA-N 0.000 claims description 2
• NOYNBCYZPDMZCJ-UHFFFAOYSA-N 1-(6-fluoro-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-8-ylurea Chemical compound C1=CN=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)F)=CC=CC2=C1 NOYNBCYZPDMZCJ-UHFFFAOYSA-N 0.000 claims description 2
• AAKPNNJMZRMCHW-UHFFFAOYSA-N 1-(6-methyl-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-8-ylurea Chemical compound C1=CN=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)C)=CC=CC2=C1 AAKPNNJMZRMCHW-UHFFFAOYSA-N 0.000 claims description 2
• WFTHPKJLXNIKMX-UHFFFAOYSA-N 1-[(4-benzyl-2,3-dihydro-1,4-benzoxazin-2-yl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NCC(OC1=CC=CC=C11)CN1CC1=CC=CC=C1 WFTHPKJLXNIKMX-UHFFFAOYSA-N 0.000 claims description 2
• XAGZJIQIVXSURR-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]piperidin-2-one Chemical group C1=CC(C(F)(F)F)=CC=C1N1C(=O)CCCC1 XAGZJIQIVXSURR-UHFFFAOYSA-N 0.000 claims description 2
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• LNRLQTQYVBBJBO-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[7-(trifluoromethyl)-3,4-dihydro-2h-chromen-4-yl]urea Chemical compound C1COC2=CC(C(F)(F)F)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 LNRLQTQYVBBJBO-UHFFFAOYSA-N 0.000 claims 3
• FDAPTCFAZHVYLK-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-[7-(trifluoromethyl)-3,4-dihydro-2h-chromen-4-yl]urea Chemical compound N1=CC=C2C(NC(=O)NC3C4=CC=C(C=C4OCC3)C(F)(F)F)=CC=CC2=C1 FDAPTCFAZHVYLK-UHFFFAOYSA-N 0.000 claims 3
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 2
• JUSPWOFSXJZIOC-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[[1-[[3-(trifluoromethyl)phenyl]methyl]-3,4-dihydro-2h-quinolin-2-yl]methyl]urea Chemical compound FC(F)(F)C1=CC=CC(CN2C3=CC=CC=C3CCC2CNC(=O)NC=2C=3C=NNC=3C=CC=2)=C1 JUSPWOFSXJZIOC-UHFFFAOYSA-N 0.000 claims 1
• YJKWUBQZJCIJET-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-1-(1H-indazol-4-yl)urea Chemical compound O1C(COC2=C1C=CC=C2)CN(C(=O)N)C2=C1C=NNC1=CC=C2 YJKWUBQZJCIJET-UHFFFAOYSA-N 0.000 claims 1
• KNVHRZOGCSRXTA-UHFFFAOYSA-N 1-(3,4-dihydro-2h-chromen-3-yl)-3-isoquinolin-5-ylurea Chemical compound N1=CC=C2C(NC(NC3CC4=CC=CC=C4OC3)=O)=CC=CC2=C1 KNVHRZOGCSRXTA-UHFFFAOYSA-N 0.000 claims 1
• YIDXTTBTOVGXQW-UHFFFAOYSA-N 1-(6-fluoro-3,4-dihydro-2h-chromen-4-yl)-3-isoquinolin-5-ylurea Chemical compound N1=CC=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)F)=CC=CC2=C1 YIDXTTBTOVGXQW-UHFFFAOYSA-N 0.000 claims 1
• JJAHUIPYJLEKHW-UHFFFAOYSA-N 1-(6-methyl-3,4-dihydro-2h-chromen-4-yl)-3-(3-methylisoquinolin-5-yl)urea Chemical compound N1=C(C)C=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)C)=CC=CC2=C1 JJAHUIPYJLEKHW-UHFFFAOYSA-N 0.000 claims 1
• OGYNVNYKCFZCQL-UHFFFAOYSA-N 1-(6-methyl-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-5-ylurea Chemical compound C1=CC=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)C)=CC=CC2=N1 OGYNVNYKCFZCQL-UHFFFAOYSA-N 0.000 claims 1
• WFZDKUJYZFGQSX-UHFFFAOYSA-N 1-(7,8-difluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C12=CC=C(F)C(F)=C2OC(C)(C)CC1NC(=O)NC1=CC=CC2=C1C=NN2 WFZDKUJYZFGQSX-UHFFFAOYSA-N 0.000 claims 1
• PFLVWBBMCOHXBI-UHFFFAOYSA-N 1-(7-tert-butyl-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-5-ylurea Chemical compound C1=CC=C2C(NC(=O)NC3C4=CC=C(C=C4OCC3)C(C)(C)C)=CC=CC2=N1 PFLVWBBMCOHXBI-UHFFFAOYSA-N 0.000 claims 1
• CJHZOBWTVLHNPM-UHFFFAOYSA-N 1-(7-tert-butyl-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-8-ylurea Chemical compound C1=CN=C2C(NC(=O)NC3C4=CC=C(C=C4OCC3)C(C)(C)C)=CC=CC2=C1 CJHZOBWTVLHNPM-UHFFFAOYSA-N 0.000 claims 1
• FAWFVJIDGASJLP-UHFFFAOYSA-N 1-[(1-benzyl-3,4-dihydro-2h-quinolin-2-yl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NCC1CCC2=CC=CC=C2N1CC1=CC=CC=C1 FAWFVJIDGASJLP-UHFFFAOYSA-N 0.000 claims 1
• VJGKAUKWFSBMMV-UHFFFAOYSA-N 1-[(1-benzyl-3,4-dihydro-2h-quinolin-2-yl)methyl]-3-isoquinolin-5-ylurea Chemical compound C=1C=CC2=CN=CC=C2C=1NC(=O)NCC1CCC2=CC=CC=C2N1CC1=CC=CC=C1 VJGKAUKWFSBMMV-UHFFFAOYSA-N 0.000 claims 1
• SHIYHNMUABYDEG-UHFFFAOYSA-N 1-[7-(3,3-dimethylbutyl)-3,4-dihydro-2h-chromen-4-yl]-3-(1h-indazol-4-yl)urea Chemical compound C1COC2=CC(CCC(C)(C)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 SHIYHNMUABYDEG-UHFFFAOYSA-N 0.000 claims 1
• XNXJLWWSCLQDSJ-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-(1,2,3,4-tetrahydroquinolin-2-ylmethyl)urea Chemical compound N1=CC=C2C(NC(NCC3NC4=CC=CC=C4CC3)=O)=CC=CC2=C1 XNXJLWWSCLQDSJ-UHFFFAOYSA-N 0.000 claims 1
• OQDKWISVFFMYFI-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-[[1-(2-phenylethyl)-3,4-dihydro-2h-quinolin-2-yl]methyl]urea Chemical compound C=1C=CC2=CN=CC=C2C=1NC(=O)NCC1CCC2=CC=CC=C2N1CCC1=CC=CC=C1 OQDKWISVFFMYFI-UHFFFAOYSA-N 0.000 claims 1
• GKMQZGBRJUQYKE-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-[[1-(3-phenylpropyl)-3,4-dihydro-2h-quinolin-2-yl]methyl]urea Chemical compound C=1C=CC2=CN=CC=C2C=1NC(=O)NCC1CCC2=CC=CC=C2N1CCCC1=CC=CC=C1 GKMQZGBRJUQYKE-UHFFFAOYSA-N 0.000 claims 1
• MTVMLXMUFHTONP-UHFFFAOYSA-N 1-quinolin-5-yl-3-[7-(trifluoromethyl)-3,4-dihydro-2h-chromen-4-yl]urea Chemical compound C1=CC=C2C(NC(=O)NC3C4=CC=C(C=C4OCC3)C(F)(F)F)=CC=CC2=N1 MTVMLXMUFHTONP-UHFFFAOYSA-N 0.000 claims 1
• RRSWDMPXVWQNGZ-UHFFFAOYSA-N methyl 4-[(1-benzyl-6-fluoro-3,4-dihydro-2h-quinolin-2-yl)methylcarbamoylamino]indazole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)N=CC2=C1NC(=O)NCC1CCC2=CC(F)=CC=C2N1CC1=CC=CC=C1 RRSWDMPXVWQNGZ-UHFFFAOYSA-N 0.000 claims 1
• AAZPBTDLYXYFLW-UHFFFAOYSA-N methyl 4-[(1-methyl-3,4-dihydro-2h-quinolin-4-yl)carbamoylamino]indazole-1-carboxylate Chemical compound C1CN(C)C2=CC=CC=C2C1NC(=O)NC1=C2C=NN(C(=O)OC)C2=CC=C1 AAZPBTDLYXYFLW-UHFFFAOYSA-N 0.000 claims 1
• MAQLVPKINKUXBG-UHFFFAOYSA-N methyl 4-[(1-propyl-3,4-dihydro-2h-quinolin-2-yl)methylcarbamoylamino]indazole-1-carboxylate Chemical compound C1CC2=CC=CC=C2N(CCC)C1CNC(=O)NC1=CC=CC2=C1C=NN2C(=O)OC MAQLVPKINKUXBG-UHFFFAOYSA-N 0.000 claims 1
• ATZWBGFHWPJTRI-UHFFFAOYSA-N methyl 4-[[1-(3-phenylpropyl)-3,4-dihydro-2h-quinolin-2-yl]methylcarbamoylamino]indazole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)N=CC2=C1NC(=O)NCC1CCC2=CC=CC=C2N1CCCC1=CC=CC=C1 ATZWBGFHWPJTRI-UHFFFAOYSA-N 0.000 claims 1
• DLGJWMIKTQGTER-UHFFFAOYSA-N methyl 4-[[1-[[2-(trifluoromethyl)phenyl]methyl]-3,4-dihydro-2h-quinolin-2-yl]methylcarbamoylamino]indazole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)N=CC2=C1NC(=O)NCC1CCC2=CC=CC=C2N1CC1=CC=CC=C1C(F)(F)F DLGJWMIKTQGTER-UHFFFAOYSA-N 0.000 claims 1
• AQTTUDHTJVHQPA-UHFFFAOYSA-N methyl 4-[[7-(trifluoromethyl)-3,4-dihydro-2h-chromen-4-yl]carbamoylamino]indazole-1-carboxylate Chemical compound C1COC2=CC(C(F)(F)F)=CC=C2C1NC(=O)NC1=C2C=NN(C(=O)OC)C2=CC=C1 AQTTUDHTJVHQPA-UHFFFAOYSA-N 0.000 claims 1
• GISBMMLRHPPKCP-UHFFFAOYSA-N methyl 4-[[8-(trifluoromethyl)-3,4-dihydro-2h-chromen-4-yl]carbamoylamino]indazole-1-carboxylate Chemical compound C1COC(C(=CC=C2)C(F)(F)F)=C2C1NC(=O)NC1=C2C=NN(C(=O)OC)C2=CC=C1 GISBMMLRHPPKCP-UHFFFAOYSA-N 0.000 claims 1
• 239000000651 prodrug Substances 0.000 abstract description 4
• 229940002612 prodrug Drugs 0.000 abstract description 4
• 239000005557 antagonist Substances 0.000 abstract description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 399
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• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 215
• 238000005481 NMR spectroscopy Methods 0.000 description 206
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• 239000002904 solvent Substances 0.000 description 167
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• 239000000047 product Substances 0.000 description 127
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• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 104
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 99
• 230000002829 reductive effect Effects 0.000 description 98
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