PT1874117E - Derivado policíclico de carbamoílpiridona possuindo actividade inibidora de hiv-integrasse - Google Patents
Derivado policíclico de carbamoílpiridona possuindo actividade inibidora de hiv-integrasse Download PDFInfo
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- PT1874117E PT1874117E PT67588434T PT06758843T PT1874117E PT 1874117 E PT1874117 E PT 1874117E PT 67588434 T PT67588434 T PT 67588434T PT 06758843 T PT06758843 T PT 06758843T PT 1874117 E PT1874117 E PT 1874117E
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- Prior art keywords
- compound
- salts
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- mmol
- hiv
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- -1 Polycyclic carbamoylpyridone derivative Chemical class 0.000 title abstract description 17
- 230000002401 inhibitory effect Effects 0.000 title abstract description 11
- 108010002459 HIV Integrase Proteins 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 13
- 102100034343 Integrase Human genes 0.000 claims description 11
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 claims description 10
- 229940124411 anti-hiv antiviral agent Drugs 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 239000012453 solvate Substances 0.000 claims description 6
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 5
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 5
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 3
- 208000031886 HIV Infections Diseases 0.000 claims description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 159000000000 sodium salts Chemical group 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- QDZZDVQGBKTLHV-UHFFFAOYSA-N (2,4-difluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1F QDZZDVQGBKTLHV-UHFFFAOYSA-N 0.000 claims 1
- 208000037357 HIV infectious disease Diseases 0.000 claims 1
- 229940092714 benzenesulfonic acid Drugs 0.000 claims 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 230000036436 anti-hiv Effects 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 abstract 2
- 125000005842 heteroatom Chemical group 0.000 abstract 2
- 239000001257 hydrogen Substances 0.000 abstract 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
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- 125000002947 alkylene group Chemical group 0.000 abstract 1
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- 150000002367 halogens Chemical class 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
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- 238000006243 chemical reaction Methods 0.000 description 21
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
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- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
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- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
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- IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 description 2
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- XPCTZQVDEJYUGT-UHFFFAOYSA-N 3-hydroxy-2-methyl-4-pyrone Chemical compound CC=1OC=CC(=O)C=1O XPCTZQVDEJYUGT-UHFFFAOYSA-N 0.000 description 2
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
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- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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Classifications
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- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
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- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
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| PT181666215T PT3372281T (pt) | 2005-04-28 | 2006-04-28 | Derivado policíclico de carbamoilpiridona possuindo atividade inibidora de hiv-integrase |
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2016
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- 2016-03-31 US US15/086,616 patent/US20160207939A1/en not_active Abandoned
- 2016-06-29 US US15/196,245 patent/US20160304535A1/en not_active Abandoned
- 2016-08-18 NO NO20161315A patent/NO340111B1/no active Protection Beyond IP Right Term
- 2016-10-11 US US15/290,094 patent/US20170029438A1/en not_active Abandoned
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2017
- 2017-02-08 US US15/427,184 patent/US20170145033A1/en not_active Abandoned
- 2017-03-27 NO NO2017010C patent/NO2017010I1/no unknown
- 2017-04-10 US US15/482,896 patent/US20170209454A1/en not_active Abandoned
- 2017-04-27 US US15/498,667 patent/US20170224694A1/en not_active Abandoned
- 2017-04-27 US US15/498,684 patent/US20170224695A1/en not_active Abandoned
- 2017-05-17 US US15/597,343 patent/US20170253616A1/en not_active Abandoned
- 2017-05-18 US US15/598,655 patent/US20170260203A1/en not_active Abandoned
- 2017-05-18 US US15/598,671 patent/US20170267693A1/en not_active Abandoned
- 2017-09-07 US US15/697,847 patent/US20170369509A1/en not_active Abandoned
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2018
- 2018-06-19 CY CY20181100633T patent/CY1120345T1/el unknown
- 2018-07-16 HK HK18109159.8A patent/HK1249742A1/en unknown
- 2018-08-16 HK HK18110519.1A patent/HK1251191A1/en unknown
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2019
- 2019-01-10 US US16/244,441 patent/US20190152990A1/en not_active Abandoned
- 2019-05-01 US US16/400,373 patent/US10927129B2/en active Active
- 2019-08-20 CY CY20191100891T patent/CY1122052T1/el unknown
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2020
- 2020-07-09 US US16/924,390 patent/US11267823B2/en not_active Expired - Lifetime
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2021
- 2021-05-10 NO NO2021018C patent/NO2021018I1/no unknown
- 2021-05-26 CY CY2021016C patent/CY2021016I2/el unknown
- 2021-06-03 BE BE2021C519C patent/BE2021C519I2/fr unknown
- 2021-06-08 NL NL301109C patent/NL301109I1/nl unknown
- 2021-06-10 FI FIC20210017C patent/FIC20210017I1/fi unknown
- 2021-06-11 FR FR21C1023C patent/FR21C1023I2/fr active Active
- 2021-06-14 HU HUS2100023C patent/HUS2100023I1/hu unknown
- 2021-06-14 HU HUS2100022C patent/HUS2100022I1/hu unknown
- 2021-06-15 LU LU00210C patent/LUC00210I2/en unknown
- 2021-06-16 LT LTPA2021512C patent/LTC2465580I2/lt unknown
- 2021-10-06 CY CY20211100866T patent/CY1124601T1/el unknown
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2022
- 2022-01-27 US US17/586,006 patent/US20220213121A1/en not_active Abandoned
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2023
- 2023-11-08 NO NO2023042C patent/NO2023042I1/no unknown
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2024
- 2024-04-09 US US18/630,561 patent/US20240279238A1/en not_active Abandoned
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