CA2260216A1

CA2260216A1 - Thiadioxobenzodiazepine inhibitors of farnesyl protein transferase

Thiadioxobenzodiazepine inhibitors of farnesyl protein transferase Download PDF

Info

Publication number: CA2260216A1
Authority: CA; Canada
Prior art keywords: tetrahydro; monohydrochloride; dioxide; ylmethyl; imidazol
Prior art date: 1996-07-15
Legal status : Abandoned

Application number

CA002260216A

Other languages

English (en)

French (fr)

Inventor

Charles Z. Ding

Current Assignee

Bristol Myers Squibb Co

Original Assignee

Individual

Priority date

1996-07-15

Filing date

1997-07-08

Publication date

1998-01-22

1997-07-08 Application filed by Individual filed Critical Individual

1998-01-22 Publication of CA2260216A1 publication Critical patent/CA2260216A1/en

Status Abandoned legal-status Critical Current

Links

102000004357 Transferases Human genes 0.000 title claims description 12
108090000992 Transferases Proteins 0.000 title claims description 12
125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 title claims description 9
239000003112 inhibitor Substances 0.000 title description 5
125000000217 alkyl group Chemical group 0.000 claims abstract description 34
125000003118 aryl group Chemical group 0.000 claims abstract description 31
239000001257 hydrogen Chemical group 0.000 claims abstract description 21
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 21
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 19
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 19
150000002431 hydrogen Chemical class 0.000 claims abstract description 16
150000003839 salts Chemical class 0.000 claims abstract description 15
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 11
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 11
239000001301 oxygen Substances 0.000 claims abstract description 11
229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
229940002612 prodrug Drugs 0.000 claims abstract description 10
239000000651 prodrug Substances 0.000 claims abstract description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 9
229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
239000011593 sulfur Substances 0.000 claims abstract description 8
102000004190 Enzymes Human genes 0.000 claims abstract description 7
108090000790 Enzymes Proteins 0.000 claims abstract description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 7
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
125000000304 alkynyl group Chemical group 0.000 claims abstract description 5
229910052799 carbon Inorganic materials 0.000 claims abstract description 5
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
239000012453 solvate Substances 0.000 claims abstract description 4
125000005017 substituted alkenyl group Chemical group 0.000 claims abstract description 4
125000004426 substituted alkynyl group Chemical group 0.000 claims abstract description 4
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 abstract description 3
101100439665 Arabidopsis thaliana SWI2 gene Proteins 0.000 claims abstract description 3
101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims abstract description 3
125000001475 halogen functional group Chemical group 0.000 claims abstract 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 109
150000001875 compounds Chemical class 0.000 claims description 100
238000000034 method Methods 0.000 claims description 23
206010028980 Neoplasm Diseases 0.000 claims description 17
201000010099 disease Diseases 0.000 claims description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
108090000623 proteins and genes Proteins 0.000 claims description 10
102000004169 proteins and genes Human genes 0.000 claims description 9
125000002837 carbocyclic group Chemical group 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
PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 claims description 4
ILPFXWWJPKBEQR-UHFFFAOYSA-N 2-[3-benzyl-8-bromo-5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]acetic acid Chemical compound C1C(CC=2C=CC=CC=2)N(CC(=O)O)SC2=CC(Br)=CC=C2N1CC1=CNC=N1 ILPFXWWJPKBEQR-UHFFFAOYSA-N 0.000 claims description 3
MEMDTLINFSXDKE-UHFFFAOYSA-N 2-[5-[[8-bromo-1,1-dioxo-2-(2-phenylethyl)-3,4-dihydro-1$l^{6},2,5-benzothiadiazepin-5-yl]methyl]imidazol-1-yl]acetamide Chemical compound NC(=O)CN1C=NC=C1CN1C2=CC=C(Br)C=C2S(=O)(=O)N(CCC=2C=CC=CC=2)CC1 MEMDTLINFSXDKE-UHFFFAOYSA-N 0.000 claims description 3
MWHBYHBPQZYXHN-UHFFFAOYSA-N 3-benzyl-5-(1h-imidazol-5-ylmethyl)-2-methylsulfonyl-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1C(CC=2C=CC=CC=2)N(S(=O)(=O)C)SC2=CC=CC=C2N1CC1=CNC=N1 MWHBYHBPQZYXHN-UHFFFAOYSA-N 0.000 claims description 3
UMQJOCAXLMBHCW-UHFFFAOYSA-N 4-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1N1SC2=CC=CC=C2N(CC=2N=CNC=2)CC1 UMQJOCAXLMBHCW-UHFFFAOYSA-N 0.000 claims description 3
FOIWREMBRDMFDU-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-8-phenyl-2-(2-phenylethyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1CN(CC=2N=CNC=2)C2=CC=C(C=3C=CC=CC=3)C=C2SN1CCC1=CC=CC=C1 FOIWREMBRDMFDU-UHFFFAOYSA-N 0.000 claims description 3
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 3
102000019337 Prenyltransferases Human genes 0.000 claims description 3
108050006837 Prenyltransferases Proteins 0.000 claims description 3
230000019491 signal transduction Effects 0.000 claims description 3
KKRUQRAUMBARKN-UHFFFAOYSA-N 2-benzyl-5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C=1NC=NC=1CN(C1=CC=CC=C1S1)CCN1CC1=CC=CC=C1 KKRUQRAUMBARKN-UHFFFAOYSA-N 0.000 claims description 2
HGKAWZWOUSSYKV-UHFFFAOYSA-N 3-benzyl-8-bromo-5-(1h-imidazol-5-ylmethyl)-2-(2-phenylethyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1C(CC=2C=CC=CC=2)N(CCC=2C=CC=CC=2)SC2=CC(Br)=CC=C2N1CC1=CNC=N1 HGKAWZWOUSSYKV-UHFFFAOYSA-N 0.000 claims description 2
KRMAQXPTWQHXJX-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-2-(2-phenylethyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1CN(CC=2N=CNC=2)C2=CC=CC=C2SN1CCC1=CC=CC=C1 KRMAQXPTWQHXJX-UHFFFAOYSA-N 0.000 claims description 2
UCDFLGARBPQRLO-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-2-(naphthalen-1-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1CN(CC=2C3=CC=CC=C3C=CC=2)SC2=CC=CC=C2N1CC1=CNC=N1 UCDFLGARBPQRLO-UHFFFAOYSA-N 0.000 claims description 2
ROTRIHULNACPAI-UHFFFAOYSA-N 8-bromo-5-(1h-imidazol-5-ylmethyl)-2-(2-phenylethyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1CN(CCC=2C=CC=CC=2)SC2=CC(Br)=CC=C2N1CC1=CNC=N1 ROTRIHULNACPAI-UHFFFAOYSA-N 0.000 claims description 2
108010006731 Dimethylallyltranstransferase Proteins 0.000 claims description 2
102000005454 Dimethylallyltranstransferase Human genes 0.000 claims description 2
RHJVIGLEIFVHIJ-UHFFFAOYSA-N cyclohexanecarboxamide Chemical compound NC(=O)C1[CH]CCCC1 RHJVIGLEIFVHIJ-UHFFFAOYSA-N 0.000 claims description 2
DPOCLPSPCAHSOZ-UHFFFAOYSA-N n-[5-(1h-imidazol-5-ylmethyl)-2-(2-phenylethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-7-yl]cyclohexanecarboxamide Chemical compound C1CCCCC1C(=O)NC(C=C1N(CC=2N=CNC=2)CC2)=CC=C1SN2CCC1=CC=CC=C1 DPOCLPSPCAHSOZ-UHFFFAOYSA-N 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims 6
ZXGMOXWPHIOFPF-UHFFFAOYSA-N 2-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1SC2=CC=CC=C2N(CC=2N=CNC=2)CC1 ZXGMOXWPHIOFPF-UHFFFAOYSA-N 0.000 claims 2
BIDTYBMVUGZXPQ-UHFFFAOYSA-N 2-[2-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]phenoxy]benzonitrile Chemical compound N#CC1=CC=CC=C1OC1=CC=CC=C1N1SC2=CC=CC=C2N(CC=2N=CNC=2)CC1 BIDTYBMVUGZXPQ-UHFFFAOYSA-N 0.000 claims 1
OBISRNPOXCNQCI-UHFFFAOYSA-N 2-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]benzamide Chemical compound NC(=O)C1=CC=CC=C1N1SC2=CC=CC=C2N(CC=2N=CNC=2)CC1 OBISRNPOXCNQCI-UHFFFAOYSA-N 0.000 claims 1
QPXVMAXFMZCZBB-UHFFFAOYSA-N 2-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]benzonitrile Chemical compound N#CC1=CC=CC=C1N1SC2=CC=CC=C2N(CC=2N=CNC=2)CC1 QPXVMAXFMZCZBB-UHFFFAOYSA-N 0.000 claims 1
BMXFAOZRTBDLEI-UHFFFAOYSA-N 2-ethyl-5-[2-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]phenyl]-1,3,4-oxadiazole Chemical compound O1C(CC)=NN=C1C1=CC=CC=C1N1SC2=CC=CC=C2N(CC=2N=CNC=2)CC1 BMXFAOZRTBDLEI-UHFFFAOYSA-N 0.000 claims 1
PIWSMVNNPWKMEQ-UHFFFAOYSA-N 3-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(N2SC3=CC=CC=C3N(CC=3N=CNC=3)CC2)=C1 PIWSMVNNPWKMEQ-UHFFFAOYSA-N 0.000 claims 1
PHBCTPWQJCMVDN-UHFFFAOYSA-N 3-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]benzonitrile Chemical compound N#CC1=CC=CC(N2SC3=CC=CC=C3N(CC=3N=CNC=3)CC2)=C1 PHBCTPWQJCMVDN-UHFFFAOYSA-N 0.000 claims 1
XKEMFTHKQRYXKW-UHFFFAOYSA-N 3-[8-bromo-5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]benzonitrile Chemical compound C1CN(C=2C=C(C=CC=2)C#N)SC2=CC(Br)=CC=C2N1CC1=CNC=N1 XKEMFTHKQRYXKW-UHFFFAOYSA-N 0.000 claims 1
WYJMLILRJURLBD-UHFFFAOYSA-N 3-benzyl-8-bromo-5-(1h-imidazol-5-ylmethyl)-2-methyl-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1C(CC=2C=CC=CC=2)N(C)SC2=CC(Br)=CC=C2N1CC1=CNC=N1 WYJMLILRJURLBD-UHFFFAOYSA-N 0.000 claims 1
SWNXJLOXHAGNFI-UHFFFAOYSA-N 3-ethyl-5-[2-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]phenyl]-1,2,4-oxadiazole Chemical compound CCC1=NOC(C=2C(=CC=CC=2)N2SC3=CC=CC=C3N(CC=3N=CNC=3)CC2)=N1 SWNXJLOXHAGNFI-UHFFFAOYSA-N 0.000 claims 1
PWWVBQDIHAXGRE-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-2-(1,3-thiazol-2-yl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C=1NC=NC=1CN(C1=CC=CC=C1S1)CCN1C1=NC=CS1 PWWVBQDIHAXGRE-UHFFFAOYSA-N 0.000 claims 1
FUBWVHYMGYGFIY-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-2-(2-methoxyphenyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound COC1=CC=CC=C1N1SC2=CC=CC=C2N(CC=2N=CNC=2)CC1 FUBWVHYMGYGFIY-UHFFFAOYSA-N 0.000 claims 1
NPJLRFNSCACJLF-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-2-(2-phenylethyl)-4,7,8,9-tetrahydro-3h-cyclopenta[h][1,2,5]benzothiadiazepine Chemical compound C1CN(CC=2N=CNC=2)C2=CC=3CCCC=3C=C2SN1CCC1=CC=CC=C1 NPJLRFNSCACJLF-UHFFFAOYSA-N 0.000 claims 1
DZIDTPYUDTUEOO-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-2-(2-phenylphenyl)-3,4-dihydro-1,2,5-benzothiadiazepin-7-amine Chemical compound C12=CC(N)=CC=C2SN(C=2C(=CC=CC=2)C=2C=CC=CC=2)CCN1CC1=CNC=N1 DZIDTPYUDTUEOO-UHFFFAOYSA-N 0.000 claims 1
QMBXDXUIVJGEPY-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-2-(2-phenylphenyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C=1NC=NC=1CN(C1=CC=CC=C1S1)CCN1C1=CC=CC=C1C1=CC=CC=C1 QMBXDXUIVJGEPY-UHFFFAOYSA-N 0.000 claims 1
RRXSVQBTHDGJNA-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-2-(2-phenylphenyl)-3,4-dihydro-1,2,5-benzothiadiazepine-8-carbonitrile Chemical compound C1CN(C=2C(=CC=CC=2)C=2C=CC=CC=2)SC2=CC(C#N)=CC=C2N1CC1=CNC=N1 RRXSVQBTHDGJNA-UHFFFAOYSA-N 0.000 claims 1
MMYXPQLLMKORLA-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-2-(3-methoxyphenyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound COC1=CC=CC(N2SC3=CC=CC=C3N(CC=3N=CNC=3)CC2)=C1 MMYXPQLLMKORLA-UHFFFAOYSA-N 0.000 claims 1
AJABEHDAANEOFM-UHFFFAOYSA-N 5-(1h-imidazol-5-ylmethyl)-n,n-dimethyl-2-(2-phenylethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-7-amine Chemical compound C1CN(CC=2N=CNC=2)C2=CC(N(C)C)=CC=C2SN1CCC1=CC=CC=C1 AJABEHDAANEOFM-UHFFFAOYSA-N 0.000 claims 1
LLJRMVXVONJIQW-UHFFFAOYSA-N 5-[2-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]phenyl]-3-(3-methylbutyl)-1,2,4-oxadiazole Chemical compound CC(C)CCC1=NOC(C=2C(=CC=CC=2)N2SC3=CC=CC=C3N(CC=3N=CNC=3)CC2)=N1 LLJRMVXVONJIQW-UHFFFAOYSA-N 0.000 claims 1
BHQQULCGBKNHGT-UHFFFAOYSA-N 7,8-dibromo-2-(2-bromo-6-phenylphenyl)-5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1=2C=C(Br)C(Br)=CC=2SN(C=2C(=CC=CC=2Br)C=2C=CC=CC=2)CCN1CC1=CNC=N1 BHQQULCGBKNHGT-UHFFFAOYSA-N 0.000 claims 1
ZAVPGYMJKFHPIK-UHFFFAOYSA-N 7,8-dibromo-5-(1h-imidazol-5-ylmethyl)-2-(2-phenylethyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1CN(CC=2N=CNC=2)C=2C=C(Br)C(Br)=CC=2SN1CCC1=CC=CC=C1 ZAVPGYMJKFHPIK-UHFFFAOYSA-N 0.000 claims 1
ZZGJUPUKUOBHQV-UHFFFAOYSA-N 7,8-dibromo-5-(1h-imidazol-5-ylmethyl)-2-(2-phenylphenyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1=2C=C(Br)C(Br)=CC=2SN(C=2C(=CC=CC=2)C=2C=CC=CC=2)CCN1CC1=CNC=N1 ZZGJUPUKUOBHQV-UHFFFAOYSA-N 0.000 claims 1
MSQBELVVUUYZCR-UHFFFAOYSA-N 8-bromo-5-(1h-imidazol-5-ylmethyl)-2-(2-phenylmethoxyphenyl)-3,4-dihydro-1,2,5-benzothiadiazepine Chemical compound C1CN(C=2C(=CC=CC=2)OCC=2C=CC=CC=2)SC2=CC(Br)=CC=C2N1CC1=CNC=N1 MSQBELVVUUYZCR-UHFFFAOYSA-N 0.000 claims 1
NLGBGQICXHKWEY-UHFFFAOYSA-N 8-bromo-5-(1h-imidazol-5-ylmethyl)-n,n-dimethyl-2-(2-phenylethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-7-amine Chemical compound C1CN(CCC=2C=CC=CC=2)SC=2C=C(Br)C(N(C)C)=CC=2N1CC1=CNC=N1 NLGBGQICXHKWEY-UHFFFAOYSA-N 0.000 claims 1
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 1
125000002686 geranylgeranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
MSVXDIMVHKZAAX-UHFFFAOYSA-N n,5-bis(1h-imidazol-5-ylmethyl)-2-(2-phenylphenyl)-3,4-dihydro-1,2,5-benzothiadiazepin-7-amine Chemical compound C=1NC=NC=1CNC(C=C12)=CC=C1SN(C=1C(=CC=CC=1)C=1C=CC=CC=1)CCN2CC1=CNC=N1 MSVXDIMVHKZAAX-UHFFFAOYSA-N 0.000 claims 1
UQSPJYQSABLBFQ-UHFFFAOYSA-N n-[5-(1h-imidazol-5-ylmethyl)-2-(2-phenylphenyl)-3,4-dihydro-1,2,5-benzothiadiazepin-7-yl]acetamide Chemical compound C12=CC(NC(=O)C)=CC=C2SN(C=2C(=CC=CC=2)C=2C=CC=CC=2)CCN1CC1=CNC=N1 UQSPJYQSABLBFQ-UHFFFAOYSA-N 0.000 claims 1
YFSKQINFBAKJLR-UHFFFAOYSA-N n-[[5-(1h-imidazol-5-ylmethyl)-2-(2-phenylphenyl)-3,4-dihydro-1,2,5-benzothiadiazepin-8-yl]methyl]acetamide Chemical compound C1CN(C=2C(=CC=CC=2)C=2C=CC=CC=2)SC2=CC(CNC(=O)C)=CC=C2N1CC1=CNC=N1 YFSKQINFBAKJLR-UHFFFAOYSA-N 0.000 claims 1
YJEPPYBRXTYBBV-UHFFFAOYSA-N n-benzyl-2-[3-benzyl-8-bromo-5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]-n-methylacetamide Chemical compound S1C2=CC(Br)=CC=C2N(CC=2N=CNC=2)CC(CC=2C=CC=CC=2)N1CC(=O)N(C)CC1=CC=CC=C1 YJEPPYBRXTYBBV-UHFFFAOYSA-N 0.000 claims 1
QBYRWOINYPQAJF-UHFFFAOYSA-N n-benzyl-2-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]-n-methylbenzamide Chemical compound C=1C=CC=C(N2SC3=CC=CC=C3N(CC=3N=CNC=3)CC2)C=1C(=O)N(C)CC1=CC=CC=C1 QBYRWOINYPQAJF-UHFFFAOYSA-N 0.000 claims 1
GMUUMWIFOBSHKR-UHFFFAOYSA-N n-benzyl-2-[5-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl]-n-methylbenzenesulfonamide Chemical compound C=1C=CC=C(N2SC3=CC=CC=C3N(CC=3N=CNC=3)CC2)C=1S(=O)(=O)N(C)CC1=CC=CC=C1 GMUUMWIFOBSHKR-UHFFFAOYSA-N 0.000 claims 1
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