NZ578296A - Fused aromatic ptp-1b inhibitors - Google Patents

Info

Publication number

NZ578296A

NZ578296A NZ578296A NZ57829608A NZ578296A NZ 578296 A NZ578296 A NZ 578296A NZ 578296 A NZ578296 A NZ 578296A NZ 57829608 A NZ57829608 A NZ 57829608A NZ 578296 A NZ578296 A NZ 578296A

Authority

NZ

New Zealand

Prior art keywords

optionally substituted

halogens

phenyl

3alkyl

group

Prior art date

2007-01-26

Links

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• 125000003118 aryl group Chemical group 0.000 title claims description 8
• 239000003801 protein tyrosine phosphatase 1B inhibitor Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 137
• 150000003839 salts Chemical class 0.000 claims abstract description 36
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 27
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 16
• 201000011510 cancer Diseases 0.000 claims abstract description 12
• 150000002367 halogens Chemical class 0.000 claims description 79
• 229910052736 halogen Inorganic materials 0.000 claims description 76
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 71
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 47
• 235000019439 ethyl acetate Nutrition 0.000 claims description 32
• 239000003112 inhibitor Substances 0.000 claims description 32
• 238000006243 chemical reaction Methods 0.000 claims description 31
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 29
• PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
• 125000001424 substituent group Chemical group 0.000 claims description 25
• 229910052739 hydrogen Inorganic materials 0.000 claims description 22
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 20
• IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 claims description 18
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• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
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• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 9
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• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
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• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 4
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 4
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 4
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• FNAQMITXJVEJKK-UHFFFAOYSA-M bromozinc(1+);1-[difluoromethyl(ethoxy)phosphoryl]oxyethane Chemical compound Br[Zn+].CCOP(=O)([C-](F)F)OCC FNAQMITXJVEJKK-UHFFFAOYSA-M 0.000 claims description 4
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 4
• 229910052757 nitrogen Inorganic materials 0.000 claims description 4
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• 230000003579 anti-obesity Effects 0.000 claims description 3
• 150000004283 biguanides Chemical class 0.000 claims description 3
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• 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims description 3
• 229910052731 fluorine Inorganic materials 0.000 claims description 3
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
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• 235000001968 nicotinic acid Nutrition 0.000 claims description 3
• 239000011664 nicotinic acid Substances 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 235000017281 sodium acetate Nutrition 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
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• PKRIGHUJDDBTDS-UHFFFAOYSA-N 6-bromo-5-iodo-2-methylquinoline Chemical compound IC1=C(Br)C=CC2=NC(C)=CC=C21 PKRIGHUJDDBTDS-UHFFFAOYSA-N 0.000 claims description 2
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