WO2016077561A1 - Oxolupene derivatives - Google Patents

Oxolupene derivatives Download PDF

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Publication number
WO2016077561A1
WO2016077561A1 PCT/US2015/060344 US2015060344W WO2016077561A1 WO 2016077561 A1 WO2016077561 A1 WO 2016077561A1 US 2015060344 W US2015060344 W US 2015060344W WO 2016077561 A1 WO2016077561 A1 WO 2016077561A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
group
mmol
substituted
cycloalkyl
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.)
Ceased
Application number
PCT/US2015/060344
Other languages
English (en)
French (fr)
Inventor
Alicia Regueiro-Ren
Zheng Liu
Jacob Swidorski
Nicholas A. Meanwell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bristol Myers Squibb Co
Original Assignee
Bristol Myers Squibb Co
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Priority to US15/524,298 priority Critical patent/US9969767B2/en
Priority to RU2017118489A priority patent/RU2017118489A/ru
Priority to AU2015346303A priority patent/AU2015346303B2/en
Priority to BR112017009850A priority patent/BR112017009850A2/pt
Priority to JP2017525933A priority patent/JP2017533937A/ja
Priority to CN201580071098.2A priority patent/CN107250153A/zh
Priority to EP15798639.9A priority patent/EP3218387A1/en
Priority to KR1020177016222A priority patent/KR20170087478A/ko
Priority to CA2967679A priority patent/CA2967679A1/en
Publication of WO2016077561A1 publication Critical patent/WO2016077561A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J63/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • C07J63/008Expansion of ring D by one atom, e.g. D homo steroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/18Antivirals for RNA viruses for HIV

Definitions

  • R 4 or R5 can be selected from the group of -CORe, -COCOR 6 ,-S0 2 R7 and -SO2NR2R2;
  • Any two adjacent R groups may combine to form an additional aryl, cycloalkyl, heteroaryl or heterocyclic ring fused to the ring initially bearing those R groups.
  • substituted lower alkylamines e.g. hydroxyl-substituted alkylamines such as diethanolamine
  • n 1-6;
  • R22 and R23 are independently selected from the group of -H, -Ci-6 alkyl, -Ci-6 substituted alkyl, and -Ci-6 cycloalkyl,
  • the mixture was stirred at -78 °C for a total of 2.5 h and was then lifted out of the cold bath and stirred for an additional 20 min at rt.
  • the mixture was placed back in the -78 °C bath and to it was added with stirring 125 mL of saturated aqueous ammonium chloride.
  • the resulting suspension was removed from the cold bath and allowed to come to rt while stirring.
  • the mixture was concentrated in vacuum to remove the organic solvent, then to the mixture was added ethyl acetate (600 mL) and water (300 mL) and the mixture was shaken and the phases were separated.
  • the organic layer was washed with water (2 x 200 mL) and with brine (50mL).
  • Step 3 Preparation of ethyl 4-((3aR,5aR,5bR,7aR,l laS,l lbR,13aS)-3a-(2-((4- chlorobenzyl)(2-(dimethylamino)ethyl)amino)- 1 -hydroxyethyl)- 1 -isopropyl-
  • a recombinant NL4-3 virus in which a section of the nef gene from NL4-3 was replaced with the Renilla luciferase gene, was used as a reference virus.
  • residue Gag P373 was converted to P373S.
  • the recombinant virus was prepared by transfection of the altered proviral clone of NL4-3. Transfections were performed in 293T cells using LipofectAMINE PLUS from Invitrogen (Carlsbad, CA), according to manufacturer's instruction. The virus was titered in MT-2 cells using luciferase enzyme activity as a marker.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
PCT/US2015/060344 2014-11-14 2015-11-12 Oxolupene derivatives Ceased WO2016077561A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
US15/524,298 US9969767B2 (en) 2014-11-14 2015-11-12 Oxolupene derivatives
RU2017118489A RU2017118489A (ru) 2014-11-14 2015-11-12 Оксолупеновые производные
AU2015346303A AU2015346303B2 (en) 2014-11-14 2015-11-12 Oxolupene derivatives
BR112017009850A BR112017009850A2 (pt) 2014-11-14 2015-11-12 composto, composição, e, uso de uma quantidade melhoradora de hiv de um composto
JP2017525933A JP2017533937A (ja) 2014-11-14 2015-11-12 オキソルペン誘導体
CN201580071098.2A CN107250153A (zh) 2014-11-14 2015-11-12 氧代羽扇豆烯衍生物
EP15798639.9A EP3218387A1 (en) 2014-11-14 2015-11-12 Oxolupene derivatives
KR1020177016222A KR20170087478A (ko) 2014-11-14 2015-11-12 옥소루펜 유도체
CA2967679A CA2967679A1 (en) 2014-11-14 2015-11-12 Oxolupene derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201462079977P 2014-11-14 2014-11-14
US62/079,977 2014-11-14

Publications (1)

Publication Number Publication Date
WO2016077561A1 true WO2016077561A1 (en) 2016-05-19

Family

ID=54697682

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2015/060344 Ceased WO2016077561A1 (en) 2014-11-14 2015-11-12 Oxolupene derivatives

Country Status (10)

Country Link
US (1) US9969767B2 (enExample)
EP (1) EP3218387A1 (enExample)
JP (1) JP2017533937A (enExample)
KR (1) KR20170087478A (enExample)
CN (1) CN107250153A (enExample)
AU (1) AU2015346303B2 (enExample)
BR (1) BR112017009850A2 (enExample)
CA (1) CA2967679A1 (enExample)
RU (1) RU2017118489A (enExample)
WO (1) WO2016077561A1 (enExample)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017017609A1 (en) * 2015-07-28 2017-02-02 Glaxosmithkline Intellectual Property (No.2) Limited Betuin derivatives for preventing or treating hiv infections
WO2017017607A1 (en) * 2015-07-28 2017-02-02 Glaxosmithkline Intellectual Property (No.2) Limited Betuin derivatives for preventing or treating hiv infections
WO2017051355A1 (en) * 2015-09-24 2017-03-30 Glaxosmithkline Intellectual Property (No.2) Limited Compounds with hiv maturation inhibitory activity
WO2017125870A1 (en) * 2016-01-20 2017-07-27 Glaxosmithkline Intellectual Property (No.2) Limited Amine derivatives of lupanes with hiv maturation inhibitory activity

Citations (17)

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Publication number Priority date Publication date Assignee Title
US5413999A (en) 1991-11-08 1995-05-09 Merck & Co., Inc. HIV protease inhibitors useful for the treatment of AIDS
US5679828A (en) 1995-06-05 1997-10-21 Biotech Research Labs, Inc. Betulinic acid and dihydrobetulinic acid derivatives and uses therefor
US20050239748A1 (en) 2004-03-17 2005-10-27 Panacos Pharmaceuticals, Inc. Pharmaceutical salts of 3-O-(3',3'-dimethylsuccinyl) betulinic acid
WO2006053255A2 (en) 2004-11-12 2006-05-18 Panacos Pharmaceuticals, Inc. Novel betulin derivatives, preparation thereof and use thereof
US7354924B2 (en) 2001-02-02 2008-04-08 Bristol-Myers Squibb Company Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
US7365221B2 (en) 2002-09-26 2008-04-29 Panacos Pharmaceuticals, Inc. Monoacylated betulin and dihydrobetulin derivatives, preparation thereof and use thereof
US20080207573A1 (en) 2006-10-16 2008-08-28 Myriad Genetics, Incorporated Compounds for treating viral infections
WO2009100532A1 (en) 2008-02-14 2009-08-20 Virochem Pharma Inc. NOVEL 17ß LUPANE DERIVATIVES
US7745625B2 (en) 2004-03-15 2010-06-29 Bristol-Myers Squibb Company Prodrugs of piperazine and substituted piperidine antiviral agents
WO2011007230A2 (en) 2009-07-14 2011-01-20 Hetero Research Foundation Lupeol-type triterpene derivatives as antivirals
US20110077227A1 (en) * 2008-01-03 2011-03-31 Christophe Moinet Novel lupane derivatives
WO2011153319A1 (en) * 2010-06-04 2011-12-08 Bristol-Myers Squibb Company C-28 amides of modified c-3 betulinic acid derivatives as hiv maturation inhibitors
WO2011153315A1 (en) * 2010-06-04 2011-12-08 Bristol-Myers Squibb Company Modified c-3 betulinic acid derivatives as hiv maturation inhibitors
WO2012106188A1 (en) * 2011-01-31 2012-08-09 Bristol-Myers Squibb Company C-28 amines of c-3 modified betulinic acid derivatives as hiv maturation inhibitors
WO2013117137A1 (en) * 2012-02-08 2013-08-15 Jiangxi Qingfeng Pharmaceutical Inc. Lupane triterpenoid derivatives and pharmaceutical use thereof
US20130210787A1 (en) 2012-02-15 2013-08-15 Bristol-Myers Squibb Company C-3 cycloalkenyl triterpenoids with hiv maturation inhibitory activity
US8846647B2 (en) 2011-01-31 2014-09-30 Bristol-Myers Squibb Company C-17 and C-3 modified triterpenoids with HIV maturation inhibitory activity

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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.
WO2009082819A1 (en) * 2008-01-03 2009-07-09 Virochem Pharma Inc. Novel lupane derivatives
EA201290632A1 (ru) * 2010-02-11 2013-03-29 ГЛАКСОСМИТКЛАЙН ЭлЭлСи Производные бетулина
JO3387B1 (ar) * 2011-12-16 2019-03-13 Glaxosmithkline Llc مشتقات بيتولين

Patent Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5413999A (en) 1991-11-08 1995-05-09 Merck & Co., Inc. HIV protease inhibitors useful for the treatment of AIDS
US5679828A (en) 1995-06-05 1997-10-21 Biotech Research Labs, Inc. Betulinic acid and dihydrobetulinic acid derivatives and uses therefor
US7354924B2 (en) 2001-02-02 2008-04-08 Bristol-Myers Squibb Company Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
US7365221B2 (en) 2002-09-26 2008-04-29 Panacos Pharmaceuticals, Inc. Monoacylated betulin and dihydrobetulin derivatives, preparation thereof and use thereof
US7745625B2 (en) 2004-03-15 2010-06-29 Bristol-Myers Squibb Company Prodrugs of piperazine and substituted piperidine antiviral agents
US20050239748A1 (en) 2004-03-17 2005-10-27 Panacos Pharmaceuticals, Inc. Pharmaceutical salts of 3-O-(3',3'-dimethylsuccinyl) betulinic acid
WO2006053255A2 (en) 2004-11-12 2006-05-18 Panacos Pharmaceuticals, Inc. Novel betulin derivatives, preparation thereof and use thereof
US20080207573A1 (en) 2006-10-16 2008-08-28 Myriad Genetics, Incorporated Compounds for treating viral infections
US20110077227A1 (en) * 2008-01-03 2011-03-31 Christophe Moinet Novel lupane derivatives
WO2009100532A1 (en) 2008-02-14 2009-08-20 Virochem Pharma Inc. NOVEL 17ß LUPANE DERIVATIVES
WO2011007230A2 (en) 2009-07-14 2011-01-20 Hetero Research Foundation Lupeol-type triterpene derivatives as antivirals
WO2011153319A1 (en) * 2010-06-04 2011-12-08 Bristol-Myers Squibb Company C-28 amides of modified c-3 betulinic acid derivatives as hiv maturation inhibitors
WO2011153315A1 (en) * 2010-06-04 2011-12-08 Bristol-Myers Squibb Company Modified c-3 betulinic acid derivatives as hiv maturation inhibitors
US8754068B2 (en) 2010-06-04 2014-06-17 Bristol-Myers Squibb Company Modified C-3 betulinic acid derivatives as HIV maturation inhibitors
US8802661B2 (en) 2010-06-04 2014-08-12 Bristol-Myers Squibb Company C-28 amides of modified C-3 betulinic acid derivatives as HIV maturation inhibitors
WO2012106188A1 (en) * 2011-01-31 2012-08-09 Bristol-Myers Squibb Company C-28 amines of c-3 modified betulinic acid derivatives as hiv maturation inhibitors
US8748415B2 (en) 2011-01-31 2014-06-10 Bristol-Myers Squibb Company C-28 amines of C-3 modified betulinic acid derivatives as HIV maturation inhibitors
US8846647B2 (en) 2011-01-31 2014-09-30 Bristol-Myers Squibb Company C-17 and C-3 modified triterpenoids with HIV maturation inhibitory activity
WO2013117137A1 (en) * 2012-02-08 2013-08-15 Jiangxi Qingfeng Pharmaceutical Inc. Lupane triterpenoid derivatives and pharmaceutical use thereof
US20130210787A1 (en) 2012-02-15 2013-08-15 Bristol-Myers Squibb Company C-3 cycloalkenyl triterpenoids with hiv maturation inhibitory activity
WO2013123019A1 (en) 2012-02-15 2013-08-22 Bristol-Myers Squibb Company C-3 cycloalkenyl triterpenoids with hiv maturation inhibitory activity

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017017609A1 (en) * 2015-07-28 2017-02-02 Glaxosmithkline Intellectual Property (No.2) Limited Betuin derivatives for preventing or treating hiv infections
WO2017017607A1 (en) * 2015-07-28 2017-02-02 Glaxosmithkline Intellectual Property (No.2) Limited Betuin derivatives for preventing or treating hiv infections
WO2017051355A1 (en) * 2015-09-24 2017-03-30 Glaxosmithkline Intellectual Property (No.2) Limited Compounds with hiv maturation inhibitory activity
CN108368071A (zh) * 2015-09-24 2018-08-03 葛兰素史克知识产权第二有限公司 具有hiv成熟抑制活性的化合物
US20180273579A1 (en) * 2015-09-24 2018-09-27 Glaxosmithkline Intellectual Property (No.2) Limited Compounds with hiv maturation inhibitory activity
WO2017125870A1 (en) * 2016-01-20 2017-07-27 Glaxosmithkline Intellectual Property (No.2) Limited Amine derivatives of lupanes with hiv maturation inhibitory activity

Also Published As

Publication number Publication date
AU2015346303B2 (en) 2018-03-15
BR112017009850A2 (pt) 2018-01-16
US20170334946A1 (en) 2017-11-23
RU2017118489A3 (enExample) 2019-02-13
CA2967679A1 (en) 2016-05-19
CN107250153A (zh) 2017-10-13
JP2017533937A (ja) 2017-11-16
US9969767B2 (en) 2018-05-15
RU2017118489A (ru) 2018-12-14
KR20170087478A (ko) 2017-07-28
AU2015346303A1 (en) 2017-06-08
EP3218387A1 (en) 2017-09-20

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