SK283408B6

SK283408B6 - Amidy a farmaceutické prostriedky na ich báze

Amidy a farmaceutické prostriedky na ich báze Download PDF

Info

Publication number: SK283408B6
Authority: SK; Slovakia
Prior art keywords: carboxylic acid; amide; trifluoromethylbiphenyl; tetrahydroisoquinolin; ylmethyl
Prior art date: 1995-06-07

Application number

SK726-96A

Other languages

English (en)

Slovak (sk)

Other versions

SK72696A3 (en

Inventor

George Chang

Peter H. Dorff

George J. Quallich

Original Assignee

Pfizer Inc.

Priority date

1995-06-07

Filing date

1995-06-07

Publication date

2003-07-01

1995-06-07 Application filed by Pfizer Inc. filed Critical Pfizer Inc.

1995-06-07 Priority claimed from PCT/IB1995/000448 external-priority patent/WO1996040640A1/en

1995-06-07 Priority claimed from CA002223574A external-priority patent/CA2223574C/en

1997-11-05 Publication of SK72696A3 publication Critical patent/SK72696A3/sk

2003-07-01 Publication of SK283408B6 publication Critical patent/SK283408B6/sk

Links

150000001408 amides Chemical class 0.000 title claims abstract description 95
239000000825 pharmaceutical preparation Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 150
102000018616 Apolipoproteins B Human genes 0.000 claims abstract description 13
108010027006 Apolipoproteins B Proteins 0.000 claims abstract description 13
201000010099 disease Diseases 0.000 claims abstract description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 10
230000028327 secretion Effects 0.000 claims abstract description 10
239000003814 drug Substances 0.000 claims abstract 5
-1 aliphatic hydrocarbylene radical Chemical class 0.000 claims description 188
125000004432 carbon atom Chemical group C* 0.000 claims description 67
IQOMYCGTGFGDFN-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IQOMYCGTGFGDFN-UHFFFAOYSA-N 0.000 claims description 51
150000003839 salts Chemical class 0.000 claims description 38
239000002253 acid Substances 0.000 claims description 34
125000003118 aryl group Chemical group 0.000 claims description 26
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
125000000217 alkyl group Chemical group 0.000 claims description 21
125000001424 substituent group Chemical group 0.000 claims description 20
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 19
229910052757 nitrogen Inorganic materials 0.000 claims description 17
238000002360 preparation method Methods 0.000 claims description 16
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
150000003254 radicals Chemical class 0.000 claims description 15
ASFAFOSQXBRFMV-LJQANCHMSA-N 3-n-(2-benzyl-1,3-dihydroxypropan-2-yl)-1-n-[(1r)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzene-1,3-dicarboxamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)C(C=1)=CC(N(C)S(C)(=O)=O)=CC=1C(=O)NC(CO)(CO)CC1=CC=CC=C1 ASFAFOSQXBRFMV-LJQANCHMSA-N 0.000 claims description 14
125000000623 heterocyclic group Chemical group 0.000 claims description 14
125000005647 linker group Chemical group 0.000 claims description 14
229920006395 saturated elastomer Polymers 0.000 claims description 12
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
125000002252 acyl group Chemical group 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
SYBKBPXOVQYFFA-UHFFFAOYSA-N 2-[2-(hydroxymethyl)-5-nitrophenyl]ethanol Chemical compound OCCC1=CC([N+]([O-])=O)=CC=C1CO SYBKBPXOVQYFFA-UHFFFAOYSA-N 0.000 claims description 9
229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
125000005842 heteroatom Chemical group 0.000 claims description 9
229940124530 sulfonamide Drugs 0.000 claims description 9
125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 8
208000008589 Obesity Diseases 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
235000020824 obesity Nutrition 0.000 claims description 8
150000003456 sulfonamides Chemical class 0.000 claims description 8
125000003282 alkyl amino group Chemical group 0.000 claims description 7
125000004414 alkyl thio group Chemical group 0.000 claims description 7
125000004429 atom Chemical group 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 7
229920002554 vinyl polymer Polymers 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000004423 acyloxy group Chemical group 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
150000004657 carbamic acid derivatives Chemical class 0.000 claims description 6
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
125000004663 dialkyl amino group Chemical group 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
150000003556 thioamides Chemical class 0.000 claims description 6
229910052727 yttrium Inorganic materials 0.000 claims description 6
208000035150 Hypercholesterolemia Diseases 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 5
206010033645 Pancreatitis Diseases 0.000 claims description 5
229920001774 Perfluoroether Polymers 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 5
125000005605 benzo group Chemical group 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
235000013877 carbamide Nutrition 0.000 claims description 5
125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
206010012601 diabetes mellitus Diseases 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
XOYOWXXIKWPXFC-UHFFFAOYSA-N n-(1,2,3,4-tetrahydroisoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CNCC2)C2=C1 XOYOWXXIKWPXFC-UHFFFAOYSA-N 0.000 claims description 5
GYPJVCGKIBMXFE-UHFFFAOYSA-N n-[3-(2-hydroxyethyl)-4-(hydroxymethyl)phenyl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=C(CO)C(CCO)=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 GYPJVCGKIBMXFE-UHFFFAOYSA-N 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
OLOIFCYZWOTWRO-UHFFFAOYSA-N tert-butyl 6-amino-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound NC1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 OLOIFCYZWOTWRO-UHFFFAOYSA-N 0.000 claims description 5
AKMALXRXYAFPLL-UHFFFAOYSA-N tert-butyl 6-nitro-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 AKMALXRXYAFPLL-UHFFFAOYSA-N 0.000 claims description 5
125000000335 thiazolyl group Chemical group 0.000 claims description 5
125000001544 thienyl group Chemical group 0.000 claims description 5
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea group Chemical group NC(=S)N UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 5
XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 5
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical group C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 4
IPDRRTURNBKLIH-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IPDRRTURNBKLIH-UHFFFAOYSA-N 0.000 claims description 4
POXYSHFMRRORKX-UHFFFAOYSA-N 2-[5-amino-2-(hydroxymethyl)phenyl]ethanol Chemical compound NC1=CC=C(CO)C(CCO)=C1 POXYSHFMRRORKX-UHFFFAOYSA-N 0.000 claims description 4
208000031226 Hyperlipidaemia Diseases 0.000 claims description 4
125000004450 alkenylene group Chemical group 0.000 claims description 4
125000004104 aryloxy group Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000002541 furyl group Chemical group 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
WXIVOQCTQSVGAQ-UHFFFAOYSA-N n-[2-(2-thiophen-2-ylacetyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)CC=3SC=CC=3)C2=C1 WXIVOQCTQSVGAQ-UHFFFAOYSA-N 0.000 claims description 4
229910052717 sulfur Chemical group 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
150000003585 thioureas Chemical class 0.000 claims description 4
150000003672 ureas Chemical class 0.000 claims description 4
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 3
IWAGGDFROAISJT-UHFFFAOYSA-N 1h-isoquinoline-2-carboxylic acid Chemical compound C1=CC=C2C=CN(C(=O)O)CC2=C1 IWAGGDFROAISJT-UHFFFAOYSA-N 0.000 claims description 3
YHOQQEDDGYYHMO-UHFFFAOYSA-N 2-[1-(trifluoromethyl)cyclohexa-2,4-dien-1-yl]benzoic acid Chemical compound FC(C1(CC=CC=C1)C=1C(=CC=CC1)C(=O)O)(F)F YHOQQEDDGYYHMO-UHFFFAOYSA-N 0.000 claims description 3
SUSWILMGRZSTML-UHFFFAOYSA-N 6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxylic acid Chemical compound C=1C=C2CN(C(=O)O)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 SUSWILMGRZSTML-UHFFFAOYSA-N 0.000 claims description 3
AVEJPRXCBCHUEY-UHFFFAOYSA-N N-(2-propan-2-ylsulfonyl-3,4-dihydro-1H-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(S(=O)(=O)C(C)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 AVEJPRXCBCHUEY-UHFFFAOYSA-N 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
125000004659 aryl alkyl thio group Chemical group 0.000 claims description 3
125000005110 aryl thio group Chemical group 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
125000004465 cycloalkenyloxy group Chemical group 0.000 claims description 3
125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
125000000842 isoxazolyl group Chemical group 0.000 claims description 3
MANDBIMAUNFYAR-UHFFFAOYSA-N n-[2-(cyclopropylcarbamothioyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=S)NC3CC3)C2=C1 MANDBIMAUNFYAR-UHFFFAOYSA-N 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
125000005592 polycycloalkyl group Polymers 0.000 claims description 3
125000000168 pyrrolyl group Chemical group 0.000 claims description 3
125000006413 ring segment Chemical group 0.000 claims description 3
239000011593 sulfur Chemical group 0.000 claims description 3
RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 claims description 2
VWDHVRYTZFLPSM-UHFFFAOYSA-N 1-(6-amino-1,2,3,4-tetrahydroisoquinolin-1-yl)butane-1-thione Chemical compound NC1=CC=C2C(C(=S)CCC)NCCC2=C1 VWDHVRYTZFLPSM-UHFFFAOYSA-N 0.000 claims description 2
ZOPPPZYLBABVSW-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1 ZOPPPZYLBABVSW-UHFFFAOYSA-N 0.000 claims description 2
125000005041 acyloxyalkyl group Chemical group 0.000 claims description 2
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
239000003524 antilipemic agent Substances 0.000 claims description 2
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
125000002619 bicyclic group Chemical group 0.000 claims description 2
125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims description 2
CUNBFJSOUZFOIJ-UHFFFAOYSA-N n-(2-but-3-enoyl-3,4-dihydro-1h-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)CC=C)C2=C1 CUNBFJSOUZFOIJ-UHFFFAOYSA-N 0.000 claims description 2
IPBZICXEEPVWTK-UHFFFAOYSA-N n-[1-(2-phenylacetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(NCC2)C(=O)CC=3C=CC=CC=3)C2=C1 IPBZICXEEPVWTK-UHFFFAOYSA-N 0.000 claims description 2
FJBJEWUBQGYKNR-UHFFFAOYSA-N n-[2-(pyridin-2-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2N=CC=CC=2)CC2)C2=C1 FJBJEWUBQGYKNR-UHFFFAOYSA-N 0.000 claims description 2
OGZZFGVXDAQWFM-UHFFFAOYSA-N n-[2-(quinolin-2-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2N=C3C=CC=CC3=CC=2)CC2)C2=C1 OGZZFGVXDAQWFM-UHFFFAOYSA-N 0.000 claims description 2
LKXVTGHTOWBADW-UHFFFAOYSA-N n-phenyl-6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)NC=3C=CC=CC=3)C2=C1 LKXVTGHTOWBADW-UHFFFAOYSA-N 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
KTKJCGKOCTXFRX-UHFFFAOYSA-N tert-butyl 6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C=1C=C2CN(C(=O)OC(C)(C)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 KTKJCGKOCTXFRX-UHFFFAOYSA-N 0.000 claims description 2
241000894007 species Species 0.000 claims 2
LZZGJMUSVKZPAO-UHFFFAOYSA-N (6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-cyclobutylmethanone Chemical compound C1CC2=CC(N)=CC=C2CN1C(=O)C1CCC1 LZZGJMUSVKZPAO-UHFFFAOYSA-N 0.000 claims 1
XGFRZMUWPZKBSK-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-2-thiophen-3-ylethanone Chemical compound C1CC2=CC(N)=CC=C2CN1C(=O)CC=1C=CSC=1 XGFRZMUWPZKBSK-UHFFFAOYSA-N 0.000 claims 1
OUMKBAHMPRLISR-UHFFFAOYSA-N 1-phenyl-4-(trifluoromethyl)benzene Chemical group C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1 OUMKBAHMPRLISR-UHFFFAOYSA-N 0.000 claims 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
OURAHGKKMQHVBA-UHFFFAOYSA-N C1CN(CC2=C1C=C(C=C2)C3=CC=CC(=C3C(=O)N)C4=CC=C(C=C4)C(F)(F)F)CC5=NC=CC=N5 Chemical compound C1CN(CC2=C1C=C(C=C2)C3=CC=CC(=C3C(=O)N)C4=CC=C(C=C4)C(F)(F)F)CC5=NC=CC=N5 OURAHGKKMQHVBA-UHFFFAOYSA-N 0.000 claims 1
UNRPAMPKONGUKM-UHFFFAOYSA-N CCCCCCN.O=C(C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1)NC1=CC=C(CN(CC2)C(NCC3=CC=CC=C3)=O)C2=C1 Chemical compound CCCCCCN.O=C(C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1)NC1=CC=C(CN(CC2)C(NCC3=CC=CC=C3)=O)C2=C1 UNRPAMPKONGUKM-UHFFFAOYSA-N 0.000 claims 1
SNEPJCYFHNDGSB-UHFFFAOYSA-N FC(OC1=C(C=CC=C1)S(=O)(=O)N1CC2=CC=C(C=C2CC1)N)(F)F.FC(C1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)O)(F)F Chemical compound FC(OC1=C(C=CC=C1)S(=O)(=O)N1CC2=CC=C(C=C2CC1)N)(F)F.FC(C1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)O)(F)F SNEPJCYFHNDGSB-UHFFFAOYSA-N 0.000 claims 1
125000003368 amide group Chemical group 0.000 claims 1
WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims 1
LBBXOYBEGXAARL-UHFFFAOYSA-N n-[2-(1,3-thiazol-2-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2SC=CN=2)CC2)C2=C1 LBBXOYBEGXAARL-UHFFFAOYSA-N 0.000 claims 1
OUIYGDVVLCXGIH-UHFFFAOYSA-N n-[2-(1h-benzimidazol-2-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2NC3=CC=CC=C3N=2)CC2)C2=C1 OUIYGDVVLCXGIH-UHFFFAOYSA-N 0.000 claims 1
HGSHHOKODPHGRI-UHFFFAOYSA-N n-[2-[2-(cyclopenten-1-yl)acetyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)CC=3CCCC=3)C2=C1 HGSHHOKODPHGRI-UHFFFAOYSA-N 0.000 claims 1
125000000565 sulfonamide group Chemical group 0.000 claims 1
LXUQDZITPQYMIR-UHFFFAOYSA-N thiourea;urea Chemical compound NC(N)=O.NC(N)=S LXUQDZITPQYMIR-UHFFFAOYSA-N 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
239000000460 chlorine Substances 0.000 description 78
239000000243 solution Substances 0.000 description 61
239000002904 solvent Substances 0.000 description 50
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 43
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 43
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
238000000034 method Methods 0.000 description 39
239000000203 mixture Substances 0.000 description 37
230000002829 reductive effect Effects 0.000 description 34
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
239000011541 reaction mixture Substances 0.000 description 25
239000007787 solid Substances 0.000 description 25
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
238000006243 chemical reaction Methods 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
229910052799 carbon Inorganic materials 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
125000004568 thiomorpholinyl group Chemical group 0.000 description 19
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
101710133386 Microsomal triacylglycerol transfer protein Proteins 0.000 description 16
239000012044 organic layer Substances 0.000 description 16
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