CA2893959A1 - Pharmaceutical compositions - Google Patents
Pharmaceutical compositions Download PDFInfo
- Publication number
- CA2893959A1 CA2893959A1 CA2893959A CA2893959A CA2893959A1 CA 2893959 A1 CA2893959 A1 CA 2893959A1 CA 2893959 A CA2893959 A CA 2893959A CA 2893959 A CA2893959 A CA 2893959A CA 2893959 A1 CA2893959 A1 CA 2893959A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- oxo
- octadecahydro
- oxobutanoic acid
- cyclopenta
- 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
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 104
- 150000003839 salts Chemical class 0.000 claims abstract description 52
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 230000002265 prevention Effects 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 567
- 239000004094 surface-active agent Substances 0.000 claims description 83
- 239000000203 mixture Substances 0.000 claims description 73
- -1 fatty acid esters Chemical class 0.000 claims description 62
- 208000031886 HIV Infections Diseases 0.000 claims description 50
- 208000037357 HIV infectious disease Diseases 0.000 claims description 43
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 43
- 239000011859 microparticle Substances 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 37
- 239000002245 particle Substances 0.000 claims description 34
- 229920000642 polymer Polymers 0.000 claims description 26
- 239000000337 buffer salt Substances 0.000 claims description 20
- 239000003381 stabilizer Substances 0.000 claims description 16
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 12
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 12
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 12
- DSNLMYRCHYFVDO-UHFFFAOYSA-N [5a,5b,8,8,11a-pentamethyl-9-(oxan-2-yloxy)-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-3a-yl]methyl 4-methylbenzenesulfonate Chemical compound C1CC(C2(CCC3C(C)(C)C(OC4OCCCC4)CCC3(C)C2CC2)C)(C)C2C2C(C(=C)C)CCC21COS(=O)(=O)C1=CC=C(C)C=C1 DSNLMYRCHYFVDO-UHFFFAOYSA-N 0.000 claims description 11
- 230000000798 anti-retroviral effect Effects 0.000 claims description 10
- 229920001223 polyethylene glycol Polymers 0.000 claims description 10
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 10
- 229920000053 polysorbate 80 Polymers 0.000 claims description 10
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 9
- 229940068968 polysorbate 80 Drugs 0.000 claims description 9
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 9
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 7
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 claims description 7
- 229960000311 ritonavir Drugs 0.000 claims description 7
- 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 claims description 7
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical group P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims description 5
- 229960002542 dolutegravir Drugs 0.000 claims description 5
- RHWKPHLQXYSBKR-BMIGLBTASA-N dolutegravir Chemical compound C([C@@H]1OCC[C@H](N1C(=O)C1=C(O)C2=O)C)N1C=C2C(=O)NCC1=CC=C(F)C=C1F RHWKPHLQXYSBKR-BMIGLBTASA-N 0.000 claims description 5
- 239000002953 phosphate buffered saline Substances 0.000 claims description 5
- 229960002814 rilpivirine Drugs 0.000 claims description 5
- YIBOMRUWOWDFLG-ONEGZZNKSA-N rilpivirine Chemical compound CC1=CC(\C=C\C#N)=CC(C)=C1NC1=CC=NC(NC=2C=CC(=CC=2)C#N)=N1 YIBOMRUWOWDFLG-ONEGZZNKSA-N 0.000 claims description 5
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- 238000011068 loading method Methods 0.000 claims description 4
- 238000012423 maintenance Methods 0.000 claims description 4
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 claims description 3
- ZAKOWWREFLAJOT-ADUHFSDSSA-N [2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] acetate Chemical group CC(=O)OC1=C(C)C(C)=C2OC(CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-ADUHFSDSSA-N 0.000 claims description 3
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 239000008389 polyethoxylated castor oil Substances 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 3
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 241000725303 Human immunodeficiency virus Species 0.000 abstract description 24
- FVWJYYTZTCVBKE-ROUWMTJPSA-N betulin Chemical group C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(CO)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C FVWJYYTZTCVBKE-ROUWMTJPSA-N 0.000 abstract description 12
- 208000015181 infectious disease Diseases 0.000 abstract description 7
- JYDNKGUBLIKNAM-UHFFFAOYSA-N Oxyallobutulin Natural products C1CC(=O)C(C)(C)C2CCC3(C)C4(C)CCC5(CO)CCC(C(=C)C)C5C4CCC3C21C JYDNKGUBLIKNAM-UHFFFAOYSA-N 0.000 abstract description 5
- 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 abstract description 5
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 392
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 98
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- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 50
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 42
- 239000000243 solution Substances 0.000 description 39
- 238000007918 intramuscular administration Methods 0.000 description 25
- 238000007920 subcutaneous administration Methods 0.000 description 24
- 230000037058 blood plasma level Effects 0.000 description 23
- 239000000725 suspension Substances 0.000 description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 21
- 238000009472 formulation Methods 0.000 description 21
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 19
- 239000003981 vehicle Substances 0.000 description 17
- 230000036470 plasma concentration Effects 0.000 description 15
- 239000007924 injection Substances 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
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- 102100034347 Integrase Human genes 0.000 description 10
- 241001024304 Mino Species 0.000 description 10
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 9
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 9
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- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 230000001954 sterilising effect Effects 0.000 description 8
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- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 7
- 239000007927 intramuscular injection Substances 0.000 description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 239000008215 water for injection Substances 0.000 description 7
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 6
- 125000000068 chlorophenyl group Chemical group 0.000 description 6
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- 238000011161 development Methods 0.000 description 6
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- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 description 4
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Classifications
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- 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
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- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (3)
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| US201261737177P | 2012-12-14 | 2012-12-14 | |
| US61/737,177 | 2012-12-14 | ||
| PCT/US2013/075196 WO2014093941A1 (en) | 2012-12-14 | 2013-12-14 | Pharmaceutical compositions |
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| CA2893959A1 true CA2893959A1 (en) | 2014-06-19 |
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|---|---|---|---|
| CA2893959A Abandoned CA2893959A1 (en) | 2012-12-14 | 2013-12-14 | Pharmaceutical compositions |
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|---|---|
| US (2) | US9795619B2 (https=) |
| EP (1) | EP2931285A4 (https=) |
| JP (1) | JP2016503030A (https=) |
| KR (1) | KR20150093819A (https=) |
| CN (1) | CN104902905A (https=) |
| AU (1) | AU2013358897B2 (https=) |
| BR (1) | BR112015013695A2 (https=) |
| CA (1) | CA2893959A1 (https=) |
| CL (1) | CL2015001660A1 (https=) |
| CR (1) | CR20150313A (https=) |
| EA (1) | EA201590862A1 (https=) |
| HK (1) | HK1209638A1 (https=) |
| IL (1) | IL238807A0 (https=) |
| MA (1) | MA38182A1 (https=) |
| MX (1) | MX2015007563A (https=) |
| PE (1) | PE20151326A1 (https=) |
| PH (1) | PH12015501156A1 (https=) |
| SG (2) | SG11201503807TA (https=) |
| WO (1) | WO2014093941A1 (https=) |
| ZA (1) | ZA201503594B (https=) |
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| JO3387B1 (ar) | 2011-12-16 | 2019-03-13 | Glaxosmithkline Llc | مشتقات بيتولين |
| KR20150093819A (ko) * | 2012-12-14 | 2015-08-18 | 글락소스미스클라인 엘엘씨 | 약제 조성물 |
| EA030003B1 (ru) | 2012-12-21 | 2018-06-29 | Джилид Сайэнс, Инк. | Полициклическое карбамоилпиридоновое соединение и его фармацевтическое применение для лечения вич-инфекции |
| US9637516B2 (en) | 2012-12-31 | 2017-05-02 | Hetero Research Foundation | Betulinic acid proline derivatives as HIV inhibitors |
| SI3019503T1 (sl) | 2013-07-12 | 2017-11-30 | Gilead Sciences, Inc. | Policiklične karbamoilpiridonske spojine in njihova uporaba za zdravljenje HIV infekcij |
| NO2865735T3 (https=) | 2013-07-12 | 2018-07-21 | ||
| NO2717902T3 (https=) | 2014-06-20 | 2018-06-23 | ||
| TWI677489B (zh) | 2014-06-20 | 2019-11-21 | 美商基利科學股份有限公司 | 多環型胺甲醯基吡啶酮化合物之合成 |
| TW201613936A (en) | 2014-06-20 | 2016-04-16 | Gilead Sciences Inc | Crystalline forms of(2R,5S,13aR)-8-hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide |
| US20170129916A1 (en) | 2014-06-26 | 2017-05-11 | Hetero Research Foundation | Novel betulinic proline imidazole derivatives as hiv inhibitors |
| US10092523B2 (en) | 2014-09-26 | 2018-10-09 | Glaxosmithkline Intellectual Property (No. 2) Limited | Long acting pharmaceutical compositions |
| TWI695003B (zh) | 2014-12-23 | 2020-06-01 | 美商基利科學股份有限公司 | 多環胺甲醯基吡啶酮化合物及其醫藥用途 |
| 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 |
| US10370405B2 (en) | 2015-03-16 | 2019-08-06 | Hetero Labs Limited | C-3 novel triterpenone with C-28 amide derivatives as HIV inhibitors |
| JP6402259B2 (ja) | 2015-04-02 | 2018-10-10 | ギリアード サイエンシーズ， インコーポレイテッド | 多環式カルバモイルピリドン化合物およびそれらの薬学的使用 |
| WO2018042332A1 (en) * | 2016-08-31 | 2018-03-08 | Glaxosmithkline Intellectual Property (No.2) Limited | Combinations and uses and treatments thereof |
| WO2018042331A1 (en) * | 2016-08-31 | 2018-03-08 | Glaxosmithkline Intellectual Property (No.2) Limited | Combinations and uses and treatments thereof |
| KR20200031658A (ko) | 2017-07-21 | 2020-03-24 | 비이브 헬쓰케어 컴퍼니 | Hib 감염 및 aids를 치료하기 위한 요법 |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8815265D0 (en) | 1988-06-27 | 1988-08-03 | Wellcome Found | Therapeutic nucleosides |
| US5358721A (en) * | 1992-12-04 | 1994-10-25 | Alza Corporation | Antiviral therapy |
| EP1292562A1 (en) | 2000-05-23 | 2003-03-19 | Univerzita palackeho V Olomouci | Triterpenoid derivatives |
| WO2003011254A1 (en) * | 2001-07-31 | 2003-02-13 | Capricorn Pharma Inc. | Amorphous drug beads |
| US20080206161A1 (en) * | 2002-10-25 | 2008-08-28 | Dov Tamarkin | Quiescent foamable compositions, steroids, kits and uses thereof |
| US20050142205A1 (en) * | 2003-07-18 | 2005-06-30 | Julia Rashba-Step | Methods for encapsulating small spherical particles prepared by controlled phase separation |
| WO2005112929A2 (en) | 2004-05-20 | 2005-12-01 | Cornell Research Foundation, Inc. | Anti-hiv-1 activity of betulinol derivatives |
| TW200628161A (en) | 2004-11-12 | 2006-08-16 | Panacos Pharmaceuticals Inc | Novel betulin derivatives, preparation thereof and use thereof |
| CN1682740A (zh) * | 2005-03-11 | 2005-10-19 | 中国药科大学 | 五环三萜类化合物在制备糖原磷酸化酶抑制剂中的应用 |
| EP1869063A2 (en) | 2005-03-29 | 2007-12-26 | Regents Of The University Of Minnesota | Methods of manufacturing bioactive 3-esters of betulinic aldehyde and betulinic acid |
| TW201414495A (zh) | 2005-04-04 | 2014-04-16 | Tibotec Pharm Ltd | Ｈｉｖ-感染之預防 |
| WO2006117666A2 (en) * | 2005-04-29 | 2006-11-09 | Pfizer Inc. | Dosage forms, pharmaceutical compositions and methods for sub-tenon delivery |
| JP2009527563A (ja) | 2006-02-21 | 2009-07-30 | アキリオン ファーマシューティカルズ，インコーポレーテッド | ウイルス感染症を治療するのに有用な置換タラキサスタン |
| FI121468B (fi) | 2006-06-07 | 2010-11-30 | Valtion Teknillinen | Betuliiniperäiset yhdisteet antimikrobisina aineina |
| EP2040671B1 (en) | 2006-06-23 | 2018-01-24 | Janssen Sciences Ireland UC | Aqueous suspensions of tmc278 |
| 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. |
| SI2175857T1 (sl) * | 2007-07-12 | 2014-01-31 | Janssen R&D Ireland | Kristalna oblika (E) 4-((4-((4-(2-cianoetenil)-2,6-dimetilfenil)amino) 2-pirimidinil)amino)benzonitrila |
| 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 |
| CN101981047A (zh) | 2008-01-03 | 2011-02-23 | Viro化学制药公司 | 新的羽扇烷衍生物 |
| DE102008037025C5 (de) * | 2008-08-08 | 2016-07-07 | Jesalis Pharma Gmbh | Verfahren zur Herstellung kristalliner Wirkstoff-Mikropartikel bzw. einer Wirkstoffpartikel-Festkörperform |
| WO2010053817A1 (en) | 2008-11-04 | 2010-05-14 | Trustees Of Dartmouth College | Betulinic acid derivatives and methods of use thereof |
| CZ301318B6 (cs) | 2008-11-13 | 2010-01-13 | Univerzita Palackého v Olomouci | 2-Deoxyglykosidy triterpenoidu, zpusob jejich prípravy a jejich použití jako lécivo |
| CA2744019C (en) * | 2008-12-11 | 2017-03-14 | Shionogi & Co., Ltd. | Synthesis of carbamoylpyridone hiv integrase inhibitors and intermediates |
| US9067966B2 (en) | 2009-07-14 | 2015-06-30 | Hetero Research Foundation, Hetero Drugs Ltd. | Lupeol-type triterpene derivatives as antivirals |
| US8802727B2 (en) | 2009-07-14 | 2014-08-12 | Hetero Research Foundation, Hetero Drugs Limited | Pharmaceutically acceptable salts of betulinic acid derivatives |
| CN102883608A (zh) * | 2010-02-11 | 2013-01-16 | 葛兰素史密丝克莱恩有限责任公司 | 白桦脂醇衍生物 |
| TWI577377B (zh) * | 2010-09-16 | 2017-04-11 | Ｖｉｉｖ醫療保健公司 | 醫藥組合物 |
| WO2013020245A1 (en) | 2011-08-08 | 2013-02-14 | Glaxosmithkline Llc | Carbonyl derivatives of betulin |
| WO2013020246A1 (en) | 2011-08-08 | 2013-02-14 | Glaxosmithkline Llc | Methylene derivatives of betulin |
| EP2791102B1 (en) | 2011-12-14 | 2016-05-18 | Glaxosmithkline LLC | Propenoate derivatives of betulin |
| JO3387B1 (ar) * | 2011-12-16 | 2019-03-13 | Glaxosmithkline Llc | مشتقات بيتولين |
| US20150209273A1 (en) | 2012-08-28 | 2015-07-30 | Glaxosmithkline Llc | Pharmaceutical Compositions |
| KR20150093819A (ko) * | 2012-12-14 | 2015-08-18 | 글락소스미스클라인 엘엘씨 | 약제 조성물 |
| US10092523B2 (en) | 2014-09-26 | 2018-10-09 | Glaxosmithkline Intellectual Property (No. 2) Limited | Long acting pharmaceutical compositions |
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- 2013-12-14 HK HK15110448.0A patent/HK1209638A1/xx unknown
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- 2013-12-14 SG SG11201503807TA patent/SG11201503807TA/en unknown
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- 2013-12-14 US US14/651,673 patent/US9795619B2/en not_active Expired - Fee Related
- 2013-12-14 JP JP2015548025A patent/JP2016503030A/ja active Pending
- 2013-12-14 MA MA38182A patent/MA38182A1/fr unknown
- 2013-12-14 CN CN201380065306.9A patent/CN104902905A/zh active Pending
- 2013-12-14 EA EA201590862A patent/EA201590862A1/ru unknown
- 2013-12-14 WO PCT/US2013/075196 patent/WO2014093941A1/en not_active Ceased
- 2013-12-14 BR BR112015013695A patent/BR112015013695A2/pt not_active IP Right Cessation
- 2013-12-14 PE PE2015000924A patent/PE20151326A1/es not_active Application Discontinuation
- 2013-12-14 SG SG10201704467SA patent/SG10201704467SA/en unknown
- 2013-12-14 CA CA2893959A patent/CA2893959A1/en not_active Abandoned
- 2013-12-14 AU AU2013358897A patent/AU2013358897B2/en not_active Ceased
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Also Published As
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| US9795619B2 (en) | 2017-10-24 |
| EP2931285A4 (en) | 2016-06-01 |
| EA201590862A1 (ru) | 2016-05-31 |
| CL2015001660A1 (es) | 2015-10-02 |
| US20150313917A1 (en) | 2015-11-05 |
| SG10201704467SA (en) | 2017-06-29 |
| IL238807A0 (en) | 2015-06-30 |
| HK1209638A1 (en) | 2016-04-08 |
| PH12015501156A1 (en) | 2015-08-10 |
| JP2016503030A (ja) | 2016-02-01 |
| MX2015007563A (es) | 2015-10-14 |
| KR20150093819A (ko) | 2015-08-18 |
| BR112015013695A2 (pt) | 2017-07-11 |
| WO2014093941A1 (en) | 2014-06-19 |
| CR20150313A (es) | 2015-10-19 |
| EP2931285A1 (en) | 2015-10-21 |
| CN104902905A (zh) | 2015-09-09 |
| AU2013358897B2 (en) | 2017-01-05 |
| MA38182A1 (fr) | 2018-04-30 |
| US20180042944A1 (en) | 2018-02-15 |
| PE20151326A1 (es) | 2015-10-12 |
| AU2013358897A1 (en) | 2015-07-02 |
| ZA201503594B (en) | 2018-11-28 |
| SG11201503807TA (en) | 2015-06-29 |
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