CA2658545A1 - Bisfuranyl protease inhibitors - Google Patents
Bisfuranyl protease inhibitors Download PDFInfo
- Publication number
- CA2658545A1 CA2658545A1 CA002658545A CA2658545A CA2658545A1 CA 2658545 A1 CA2658545 A1 CA 2658545A1 CA 002658545 A CA002658545 A CA 002658545A CA 2658545 A CA2658545 A CA 2658545A CA 2658545 A1 CA2658545 A1 CA 2658545A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- alkoxy
- alkylamino
- alkylthio
- arylamino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title abstract description 5
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 179
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 20
- 206010059866 Drug resistance Diseases 0.000 claims abstract description 17
- 241001465754 Metazoa Species 0.000 claims abstract description 12
- -1 nitro, carboxy, hydroxy Chemical group 0.000 claims description 99
- 125000003545 alkoxy group Chemical group 0.000 claims description 79
- 125000003282 alkyl amino group Chemical group 0.000 claims description 77
- 238000000034 method Methods 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 125000004414 alkyl thio group Chemical group 0.000 claims description 63
- 125000001769 aryl amino group Chemical group 0.000 claims description 63
- 125000005110 aryl thio group Chemical group 0.000 claims description 63
- 125000004104 aryloxy group Chemical group 0.000 claims description 63
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 125000003118 aryl group Chemical group 0.000 claims description 42
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 41
- 125000003342 alkenyl group Chemical group 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002367 halogens Chemical group 0.000 claims description 28
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
- 125000000304 alkynyl group Chemical group 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 19
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 19
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 16
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 16
- 125000005128 aryl amino alkyl group Chemical group 0.000 claims description 16
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 15
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 15
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 14
- 125000001188 haloalkyl group Chemical group 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 13
- 241000700605 Viruses Species 0.000 claims description 11
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 8
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 108091005804 Peptidases Proteins 0.000 claims description 7
- 239000004365 Protease Substances 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 5
- 101100495911 Arabidopsis thaliana CHR10 gene Proteins 0.000 claims description 4
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000004791 2-fluoroethoxy group Chemical group FCCO* 0.000 claims 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 2
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 110
- 239000011541 reaction mixture Substances 0.000 description 61
- 235000019439 ethyl acetate Nutrition 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 238000003756 stirring Methods 0.000 description 29
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- 230000002829 reductive effect Effects 0.000 description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 24
- 230000015572 biosynthetic process Effects 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 23
- 239000012074 organic phase Substances 0.000 description 21
- 239000007787 solid Substances 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 18
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 14
- 241000725303 Human immunodeficiency virus Species 0.000 description 13
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 101100160255 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YLR154C-H gene Proteins 0.000 description 12
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 11
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- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
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- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000006626 methoxycarbonylamino group Chemical group 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- 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
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FZMZNAWBMQKJRL-UHFFFAOYSA-N tert-butyl n-(1-hydroxyethyl)carbamate Chemical compound CC(O)NC(=O)OC(C)(C)C FZMZNAWBMQKJRL-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
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- 239000001993 wax Substances 0.000 description 1
- 229960002555 zidovudine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- 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
-
- 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)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83288206P | 2006-07-24 | 2006-07-24 | |
| US60/832,882 | 2006-07-24 | ||
| PCT/US2007/016691 WO2008013834A1 (en) | 2006-07-24 | 2007-07-24 | Bisfuranyl protease inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2658545A1 true CA2658545A1 (en) | 2008-01-31 |
Family
ID=38739458
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002658545A Abandoned CA2658545A1 (en) | 2006-07-24 | 2007-07-24 | Bisfuranyl protease inhibitors |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US20080070910A1 (enExample) |
| EP (1) | EP2069356A1 (enExample) |
| JP (1) | JP2009544708A (enExample) |
| AU (1) | AU2007277253A1 (enExample) |
| CA (1) | CA2658545A1 (enExample) |
| WO (1) | WO2008013834A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8592487B2 (en) | 2007-10-26 | 2013-11-26 | Concert Pharmaceuticals, Inc. | Deuterated darunavir |
| FR2941696B1 (fr) | 2009-02-05 | 2011-04-15 | Sanofi Aventis | Derives d'azaspiranyl-alkylcarbamates d'heterocycles a 5 chainons, leur preparation et leur application en therapeutique |
| FR2945531A1 (fr) | 2009-05-12 | 2010-11-19 | Sanofi Aventis | Derives de 7-aza-spiro°3,5!nonane-7-carboxylates, leur preparation et leur application en therapeutique |
| FR2945534B1 (fr) | 2009-05-12 | 2012-11-16 | Sanofi Aventis | DERIVES DE CYCLOPENTAL[c]PYRROLE-2-CARBOXYLATES, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
| FR2945533B1 (fr) | 2009-05-12 | 2011-05-27 | Sanofi Aventis | Derives de cyclopenta°c!pyrrolyl-alkylcarbamates d'heterocycles a 5 chainons, leur preparation et leur application en therapeutique |
| AU2010313085A1 (en) * | 2009-10-30 | 2012-05-31 | Lupin Limited | A novel process for preparation of darunavir and darunavir ethanolate of fine particle size |
| WO2011061590A1 (en) | 2009-11-17 | 2011-05-26 | Hetero Research Foundation | Novel carboxamide derivatives as hiv inhibitors |
| US9220710B2 (en) * | 2013-01-09 | 2015-12-29 | Gilead Sciences, Inc. | Therapeutic compounds |
| EP3142659B1 (en) * | 2014-05-16 | 2021-03-24 | Purdue Research Foundation | Hiv-1 protease inhibitors and uses thereof |
| WO2016039403A1 (ja) * | 2014-09-11 | 2016-03-17 | 塩野義製薬株式会社 | 持続性ｈｉｖプロテアーゼ阻害剤 |
| CN118286245A (zh) | 2014-12-26 | 2024-07-05 | 埃莫里大学 | N4-羟基胞苷和衍生物及与其相关的抗病毒用途 |
| CN104910103A (zh) * | 2015-04-23 | 2015-09-16 | 上海应用技术学院 | 一种地瑞那韦中间体的制备方法 |
| DK3337567T3 (da) | 2015-08-17 | 2021-12-06 | Purdue Research Foundation | Hiv-1-proteasehæmmere og anvendelser deraf |
| CN105439997B (zh) * | 2015-11-13 | 2018-03-27 | 新疆农垦科学院 | 一种克百威氨基化半抗原的合成方法及应用 |
| CN105399711B (zh) * | 2015-11-13 | 2018-03-27 | 新疆农垦科学院 | 一种克百威羧基化半抗原的合成方法 |
| US11331331B2 (en) | 2017-12-07 | 2022-05-17 | Emory University | N4-hydroxycytidine and derivatives and anti-viral uses related thereto |
| US20230136594A1 (en) * | 2020-03-18 | 2023-05-04 | Purdue Research Foundation | Tricyclic p2-ligand containing potent hiv-protease inhibitors |
| US12083099B2 (en) | 2020-10-28 | 2024-09-10 | Accencio LLC | Methods of treating symptoms of coronavirus infection with viral protease inhibitors |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5728718A (en) * | 1994-12-20 | 1998-03-17 | The United States Of America As Represented By The Department Of Health And Human Services | 2,5-diamino-3,4-disubstituted-1,6-diphenylhexane isosteres comprising benzamide, sulfonamide and anthranilamide subunits and methods of using same |
| WO1999067254A2 (en) * | 1998-06-23 | 1999-12-29 | The United States Of America Represented By The Secretary, Department Of Health And Human Services | Multi-drug resistant retroviral protease inhibitors and use thereof |
| ATE500823T1 (de) * | 1998-06-23 | 2011-03-15 | Us Of America Represented By The Secretary Dept Of Health And Human Services | Arzneimittel zur behandlung von hiv-infizierten säugetieren |
| AR031520A1 (es) * | 1999-06-11 | 2003-09-24 | Vertex Pharma | Un compuesto inhibidor de aspartilo proteasa, una composicion que lo comprende y un metodo para tratar un paciente con dicha composicion |
| CA2386850C (en) * | 1999-10-06 | 2010-03-30 | Piet Tom Bert Paul Wigerinck | Hexahydrofuro[2,3-b]furan-3-yl-n-{3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-1-benzyl-2-hydroxypropyl} carbamate as retroviral protease inhibitor |
| US7157489B2 (en) * | 2002-03-12 | 2007-01-02 | The Board Of Trustees Of The University Of Illinois | HIV protease inhibitors |
| JP4942915B2 (ja) * | 2002-04-26 | 2012-05-30 | ギリアード サイエンシーズ， インコーポレイテッド | Ｈｉｖプロテアーゼ阻害剤化合物のホスホネートアナログの細胞蓄積 |
-
2007
- 2007-07-24 US US11/880,743 patent/US20080070910A1/en not_active Abandoned
- 2007-07-24 WO PCT/US2007/016691 patent/WO2008013834A1/en not_active Ceased
- 2007-07-24 US US12/307,634 patent/US20090312318A1/en not_active Abandoned
- 2007-07-24 JP JP2009521811A patent/JP2009544708A/ja active Pending
- 2007-07-24 AU AU2007277253A patent/AU2007277253A1/en not_active Abandoned
- 2007-07-24 EP EP07836224A patent/EP2069356A1/en not_active Withdrawn
- 2007-07-24 CA CA002658545A patent/CA2658545A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2007277253A1 (en) | 2008-01-31 |
| WO2008013834A1 (en) | 2008-01-31 |
| US20090312318A1 (en) | 2009-12-17 |
| JP2009544708A (ja) | 2009-12-17 |
| EP2069356A1 (en) | 2009-06-17 |
| US20080070910A1 (en) | 2008-03-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |