JP5872074B2 - ルパントリテルペノイド誘導体およびその薬学的使用 - Google Patents
ルパントリテルペノイド誘導体およびその薬学的使用 Download PDFInfo
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- JP5872074B2 JP5872074B2 JP2014555064A JP2014555064A JP5872074B2 JP 5872074 B2 JP5872074 B2 JP 5872074B2 JP 2014555064 A JP2014555064 A JP 2014555064A JP 2014555064 A JP2014555064 A JP 2014555064A JP 5872074 B2 JP5872074 B2 JP 5872074B2
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- independently
- compound
- mmol
- dichloromethane
- alkyl
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- 241000219745 Lupinus Species 0.000 title description 8
- 150000003648 triterpenes Chemical class 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 493
- 125000000217 alkyl group Chemical group 0.000 claims description 79
- 150000003839 salts Chemical class 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 125000001072 heteroaryl group Chemical group 0.000 claims description 29
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 23
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 23
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000001188 haloalkyl group Chemical group 0.000 claims description 21
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 21
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 9
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 8
- 125000004001 thioalkyl group Chemical group 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 208000031886 HIV Infections Diseases 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 3
- 229940042404 nucleoside and nucleotide reverse transcriptase inhibitor Drugs 0.000 claims description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 230000036436 anti-hiv Effects 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 238000002648 combination therapy Methods 0.000 claims description 2
- 229940125777 fusion inhibitor Drugs 0.000 claims description 2
- 229940124524 integrase inhibitor Drugs 0.000 claims description 2
- 239000002850 integrase inhibitor Substances 0.000 claims description 2
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 claims description 2
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000003981 vehicle Substances 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
- 125000005549 heteroarylene group Chemical group 0.000 claims 2
- 238000013329 compounding Methods 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 544
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 212
- 239000007787 solid Substances 0.000 description 207
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 159
- 230000015572 biosynthetic process Effects 0.000 description 154
- 238000003786 synthesis reaction Methods 0.000 description 154
- 239000000243 solution Substances 0.000 description 148
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 120
- 238000000034 method Methods 0.000 description 117
- 239000000203 mixture Substances 0.000 description 114
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 108
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 95
- 229910052938 sodium sulfate Inorganic materials 0.000 description 94
- 235000011152 sodium sulphate Nutrition 0.000 description 94
- 239000012267 brine Substances 0.000 description 91
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 91
- 238000000746 purification Methods 0.000 description 85
- 239000011541 reaction mixture Substances 0.000 description 73
- 235000019439 ethyl acetate Nutrition 0.000 description 71
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 56
- -1 methylene, carbonyl Chemical group 0.000 description 55
- 239000003208 petroleum Substances 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 45
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- 239000012074 organic phase Substances 0.000 description 45
- 238000012746 preparative thin layer chromatography Methods 0.000 description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 33
- 150000005840 aryl radicals Chemical class 0.000 description 33
- 239000012047 saturated solution Substances 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- 239000000741 silica gel Substances 0.000 description 31
- 229910002027 silica gel Inorganic materials 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- 239000012046 mixed solvent Substances 0.000 description 30
- 239000011734 sodium Substances 0.000 description 30
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 28
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 27
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 27
- 125000005843 halogen group Chemical group 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
- 238000004587 chromatography analysis Methods 0.000 description 21
- HJPDRTSDGCUAIO-UHFFFAOYSA-N 3,3-dimethyl-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoic acid Chemical compound CC(C)(C)OC(=O)C(C)(C)CC(O)=O HJPDRTSDGCUAIO-UHFFFAOYSA-N 0.000 description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 description 20
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 14
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 14
- 125000004093 cyano group Chemical group *C#N 0.000 description 13
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 235000011054 acetic acid Nutrition 0.000 description 12
- 239000006260 foam Substances 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- 241000725303 Human immunodeficiency virus Species 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 239000007821 HATU Substances 0.000 description 8
- YTDSHPUZEWSEHU-UHFFFAOYSA-N cyano hydrogen carbonate Chemical compound OC(=O)OC#N YTDSHPUZEWSEHU-UHFFFAOYSA-N 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 7
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 4
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- 125000000304 alkynyl group Chemical group 0.000 description 4
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- MVIRREHRVZLANQ-UHFFFAOYSA-N betulin Natural products CC(=O)OC1CCC2(C)C(CCC3(C)C2CC=C4C5C(CCC5(CO)CCC34C)C(=C)C)C1(C)C MVIRREHRVZLANQ-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
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- CZFNISFYDPIDNM-UHFFFAOYSA-N n,n-dimethylformamide;oxolane Chemical compound CN(C)C=O.C1CCOC1 CZFNISFYDPIDNM-UHFFFAOYSA-N 0.000 description 1
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- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
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- 239000002773 nucleotide Substances 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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- 239000002245 particle Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
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- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
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- 230000007017 scission Effects 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
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- IHMQNZFRFVYNDS-UHFFFAOYSA-N tert-butyl n-amino-n-methylcarbamate Chemical compound CN(N)C(=O)OC(C)(C)C IHMQNZFRFVYNDS-UHFFFAOYSA-N 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/433—Thidiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210027090 | 2012-02-08 | ||
| CN201210027090.4 | 2012-02-08 | ||
| CN201310014849.XA CN103242413B (zh) | 2012-02-08 | 2013-01-15 | Lupane三萜系衍生物及其药学用途 |
| CN201310014849.X | 2013-01-15 | ||
| PCT/CN2013/071100 WO2013117137A1 (en) | 2012-02-08 | 2013-01-30 | Lupane triterpenoid derivatives and pharmaceutical use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2015505545A JP2015505545A (ja) | 2015-02-23 |
| JP5872074B2 true JP5872074B2 (ja) | 2016-03-01 |
Family
ID=48922317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014555064A Expired - Fee Related JP5872074B2 (ja) | 2012-02-08 | 2013-01-30 | ルパントリテルペノイド誘導体およびその薬学的使用 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US9428542B2 ( ) |
| EP (1) | EP2812343B1 ( ) |
| JP (1) | JP5872074B2 ( ) |
| KR (1) | KR20140126739A ( ) |
| CN (1) | CN103242413B ( ) |
| AU (1) | AU2013218441A1 ( ) |
| BR (1) | BR112014018953A8 ( ) |
| CA (1) | CA2860581A1 ( ) |
| EA (1) | EA201491479A1 ( ) |
| HK (1) | HK1202553A1 ( ) |
| WO (1) | WO2013117137A1 ( ) |
| ZA (1) | ZA201405819B ( ) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014105926A1 (en) | 2012-12-31 | 2014-07-03 | Hetero Research Foundation | Novel betulinic acid proline derivatives as hiv inhibitors |
| US20170129916A1 (en) | 2014-06-26 | 2017-05-11 | Hetero Research Foundation | Novel betulinic proline imidazole derivatives as hiv inhibitors |
| EP3218387A1 (en) * | 2014-11-14 | 2017-09-20 | VIIV Healthcare UK (No.5) Limited | Oxolupene derivatives |
| WO2016077572A1 (en) * | 2014-11-14 | 2016-05-19 | Bristol-Myers Squibb Company | Extended betulinic acid analogs |
| EP3218388A1 (en) * | 2014-11-14 | 2017-09-20 | VIIV Healthcare UK (No.5) Limited | C17-aryl substituted betulinic acid analogs |
| MA40886B1 (fr) | 2015-02-09 | 2020-03-31 | Hetero Research Foundation | Nouveau triterpénone en c-3 avec des dérivés d'amide inverse en c-28 en tant qu'inhibiteurs du vih |
| WO2016147099A2 (en) | 2015-03-16 | 2016-09-22 | Hetero Research Foundation | C-3 novel triterpenone with c-28 amide derivatives as hiv inhibitors |
| WO2018029602A1 (en) * | 2016-08-08 | 2018-02-15 | Hetero Labs Limited | C-3 novel triterpenone with c-28 heterocycle derivatives as hiv inhibitors |
| WO2018029604A1 (en) * | 2016-08-08 | 2018-02-15 | Hetero Labs Limited | C-3 novel triterpenone with c-17 reverse amide derivatives as hiv inhibitors |
| WO2018029610A1 (en) * | 2016-08-09 | 2018-02-15 | Hetero Labs Limited | C-3 novel triterpenone with c-17 n-amide derivatives as hiv inhibitors |
| WO2018065930A1 (en) * | 2016-10-05 | 2018-04-12 | Hetero Labs Limited | C-3 triterpenone with c-17 reverse amide derivatives as hiv inhibitors |
| WO2018069857A1 (en) * | 2016-10-12 | 2018-04-19 | Hetero Labs Limited | C-3 novel triterpenone with c-17 reverse amide heterocycle derivatives as hiv inhibitors |
| WO2019150300A1 (en) | 2018-02-02 | 2019-08-08 | Glaxosmithkline Intellectual Property (No.2) Limited | Crystalline forms of 4-(((3ar,5ar,5br,7ar,9s,11ar,11br,13as)-3a-((r)-2-((4-chlorobenzyl)(2-(dimethylamino)ethyl)amino)-1-hydroxyethyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2h-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid |
| PL237998B1 (pl) | 2018-05-28 | 2021-06-28 | Narodowy Inst Lekow | Fosfonowe pochodne kwasu 3-karboksyacylobetulinowego, sposób ich otrzymywania oraz ich zastosowanie |
| CN114369134A (zh) * | 2020-10-15 | 2022-04-19 | 江西青峰药业有限公司 | 一种Lupane三萜系衍生物葡甲胺盐无定型物及其制备方法和应用 |
| CN115504947B (zh) * | 2022-08-23 | 2024-04-26 | 山东和源制药有限公司 | 一种呋喃酮酸的制备方法 |
| CN116041415B (zh) * | 2023-02-01 | 2023-08-18 | 吉林农业大学 | 一种裂环羽扇豆烷衍生物及其制备方法与应用 |
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| WO2008127364A2 (en) * | 2006-10-13 | 2008-10-23 | Myriad Genetics, Inc. | Antiviral compounds and use thereof |
| AR063546A1 (es) * | 2006-11-03 | 2009-01-28 | Panacos Pharmaceuticals Inc | DERIVADOS DE TRITERPENO, METODOS PARA SU PREPARACION, COMPOSICIONES FARMACEUTICAS QUE LOS COMPRENDEN Y SU USO EN LA FABRICACION DE MEDICAMENTOS PARA EL TRATAMIENTO DE INFECCIoN POR EL VIRUS VIH. |
| WO2009073818A1 (en) * | 2007-12-04 | 2009-06-11 | Myriad Genetics, Inc. | Compounds and therapeutic use thereof |
| JP2011508748A (ja) * | 2008-01-03 | 2011-03-17 | バイロケム ファーマ インコーポレイテッド | 新規のルパン誘導体 |
| CN101977924A (zh) * | 2008-01-03 | 2011-02-16 | Viro化学制药公司 | 新的c-21-酮基羽扇烷衍生物、其制备方法和应用 |
| JP2013519674A (ja) | 2010-02-11 | 2013-05-30 | グラクソスミスクライン エルエルシー | ベツリンの誘導体 |
| JO3387B1 (ar) * | 2011-12-16 | 2019-03-13 | Glaxosmithkline Llc | مشتقات بيتولين |
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- 2013-01-30 AU AU2013218441A patent/AU2013218441A1/en not_active Abandoned
- 2013-01-30 CA CA2860581A patent/CA2860581A1/en not_active Abandoned
- 2013-01-30 US US14/374,832 patent/US9428542B2/en not_active Expired - Fee Related
- 2013-01-30 EP EP13746137.2A patent/EP2812343B1/en active Active
- 2013-01-30 JP JP2014555064A patent/JP5872074B2/ja not_active Expired - Fee Related
- 2013-01-30 KR KR1020147025188A patent/KR20140126739A/ko not_active Application Discontinuation
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| HK1202553A1 (en) | 2015-10-02 |
| AU2013218441A1 (en) | 2014-07-24 |
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| JP2015505545A (ja) | 2015-02-23 |
| KR20140126739A (ko) | 2014-10-31 |
| WO2013117137A1 (en) | 2013-08-15 |
| CN103242413B (zh) | 2015-08-26 |
| EA201491479A1 (ru) | 2014-11-28 |
| EP2812343B1 (en) | 2019-03-13 |
| ZA201405819B (en) | 2015-12-23 |
| BR112014018953A8 (pt) | 2017-07-11 |
| CN103242413A (zh) | 2013-08-14 |
| EP2812343A1 (en) | 2014-12-17 |
| US20150011517A1 (en) | 2015-01-08 |
| BR112014018953A2 ( ) | 2017-06-20 |
| EP2812343A4 (en) | 2015-12-02 |
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