DK2751072T3 - Krystallinsk diacylhydrazin og anvendelsen deraf - Google Patents
Krystallinsk diacylhydrazin og anvendelsen deraf Download PDFInfo
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- DK2751072T3 DK2751072T3 DK12829775.1T DK12829775T DK2751072T3 DK 2751072 T3 DK2751072 T3 DK 2751072T3 DK 12829775 T DK12829775 T DK 12829775T DK 2751072 T3 DK2751072 T3 DK 2751072T3
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- C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
- C07C243/38—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to carbon atoms of six-membered aromatic rings
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Claims (7)
1. Krystallinsk (R)-3,5-dimethylbenzoesyre-N-(1 -tert-buty I buty I )-N ’-(2-ethy I-3-methoxybenzoyl)-hydrazid Form III, der er kendetegnet ved at have et pulverrøntgendiffraktionsmønster med toppe ved 8,14, 8,52, 9,62, 11,02, 11,90, 5 12,16, 14,02, 14,62, 17,00, 17,88, 18,56, 19,02, 19,24, 20,51,20,93, 22,19, 22,73, 23,22, 24,31, 24,53, 25,91,26,22, 27,36, 27,73, 28,70, 30,84, 31,52, 32,30, 33,19 og 34,39 grader 2Θ. 2. (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3- 10 methoxybenzoyl)-hydrazid Form III ifølge krav 1, hvor (R)-3,5- dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3-methoxybenzoyl)-hydrazid er ren Form III. 3. (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3- 15 methoxybenzoyl)-hydrazid Form III ifølge krav 1 eller 2 med en gennemsnitlig partikelstørrelsesfordeling på ca. 10 pm eller mindre.
4. Sammensætning, der omfatter (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3-methoxybenzoyl)-hydrazid Form III ifølge et hvilket 20 som helst af kravene 1 -3 og et eller flere excipienser.
5. Sammensætning ifølge krav 4, hvor det ene eller de flere excipienser omfatter et eller flere farmaceutisk acceptable excipienser valgt fra gruppen, der består af Miglyol 812, phospholipon 90G eller 25 tocopherylpolyethylenglycol 1000-succinat eller en blanding deraf.
6. Fremgangsmåde til regulering af genekspressionen af et gen af interesse i en isoleret værtscelle, hvilken fremgangsmåde omfatter etablering af kontakt mellem værtscellen og sammensætningen ifølge krav 4, hvor værtscellen 30 omfatter et polynucleotid, der koder for et genskifte, der omfatter et ligandbindingsdomæne, der binder (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N'-(2-ethyl-3-methoxybenzoyl)-hydrazid. 7. (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3- 35 methoxybenzoyl)-hydrazid Form III ifølge et hvilket som helst af kravene 1-3 til anvendelse til behandling afen sygdom, forstyrrelse, skade eller tilstand hos et individ. 8. (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3- 10 methoxybenzoyl)-hydrazid Form III til anvendelse ifølge krav 7, hvor en værtscelle i individet omfatter et polynukleotid, der koder for et genskifte, der omfatter et ligandbindingsdomæne, der binder (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3-methoxybenzoyl)-hydrazid. 15 9. (R)-3,5-dimethylbenzoesyre-N-(1 -tert-butylbutyl)-N’-(2-ethyl-3- methoxybenzoyl)-hydrazid Form III til anvendelse ifølge krav 8, hvor sygdommen, forstyrrelsen, skaden eller tilstanden er valgt fra gruppen, der består af cancer, en metabolisk relateret forstyrrelse, nyresygdom, anæmi, en autoimmun forstyrrelse, en øjenforstyrrelse, en blodforstyrrelse, en neurologisk forstyrrelse, en lungeforstyrrelse, en reumatologisk forstyrrelse og en infektionssygdom. 5 10. (R)-3,5-dimethylbenzoesyre-N-(1 -tert-butylbutyl)-N’-(2-ethyl-3- methoxybenzoyl)-hydrazid Form III til anvendelse ifølge krav 8, hvor genskiftet omfatter et ecdysonreceptor-ligandbindingsdomæne. 11. (R)-3,5-dimethylbenzoesyre-N-(1 -tert-buty I butyl )-N ’-(2-ethy I-3- 10 methoxybenzoyl)-hydrazid Form III til anvendelse ifølge krav 10, hvor værtscellen yderligere omfatter et polynukleotid, der koder for et peptid, protein eller polypeptid, hvis ekspression reguleres af genskiftet. 12. (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3- 15 methoxybenzoyl)-hydrazid Form III til anvendelse ifølge krav 11, hvor polynukleotidet koder for IL-12 eller en subunit deraf.
13. Fremgangsmåde til bekæmpelse af insekter, hvilken fremgangsmåde omfatter etablering af kontakt mellem insekterne eller deres habitat og en 20 insekticidalt effektiv mængde af (R)-3,5-dimethylbenzoesyre-N-(1 -tert- butylbutyl)-N’-(2-ethyl-3-methoxybenzoyl)-hydrazid Form III ifølge et hvilket som helst af kravene 1-3 eller en sammensætning deraf.
14. Fremgangsmåde til fremstilling af det rene krystallinske (R)-3,5- 25 dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3-methoxybenzoyl)- hydrazid Form III ifølge krav 2, hvilken fremgangsmåde omfatter: (a) ækvilibrering af en suspension af krystallinsk eller amorf (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3-methoxybenzoyl)-hydrazid i mindst 0,5 time i et eller flere ikke-solvatdannende 30 opløsningsmidler ved ca. 26 °C eller derunder; og (b) isolering det rene krystallinske (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2-ethyl-3-methoxybenzoyl)-hydrazid Form III.
15. Kit, der omfatter (R)-3,5-dimethylbenzoesyre-N-(1-tert-butylbutyl)-N’-(2- 35 ethyl-3-methoxybenzoyl)-hydrazid Form III ifølge et hvilket som helst af kravene 1-3.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161532368P | 2011-09-08 | 2011-09-08 | |
PCT/US2012/054141 WO2013036758A1 (en) | 2011-09-08 | 2012-09-07 | Crystalline diacylhydrazine and the use thereof |
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DK2751072T3 true DK2751072T3 (da) | 2019-03-04 |
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DK12829775.1T DK2751072T3 (da) | 2011-09-08 | 2012-09-07 | Krystallinsk diacylhydrazin og anvendelsen deraf |
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US (4) | US8946294B2 (da) |
EP (2) | EP2751072B1 (da) |
JP (3) | JP6347745B2 (da) |
KR (3) | KR102256613B1 (da) |
CN (3) | CN106187812A (da) |
AU (1) | AU2013201096B2 (da) |
BR (1) | BR112014005509B1 (da) |
CA (2) | CA2848222C (da) |
DK (1) | DK2751072T3 (da) |
ES (1) | ES2710212T3 (da) |
HK (2) | HK1199870A1 (da) |
IL (1) | IL231310B (da) |
MX (3) | MX350158B (da) |
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CA2848222C (en) | 2011-09-08 | 2020-06-16 | Intrexon Corporation | Crystalline diacylhydrazine and the use thereof |
ES2954451T3 (es) * | 2014-08-22 | 2023-11-22 | Biocryst Pharm Inc | Composiciones y usos de derivados de amidina |
US20180200209A1 (en) * | 2015-07-10 | 2018-07-19 | Millendo Therapeutics, Inc. | Enhanced bioavailability of n-(2,6-bis(1-methylethyl)phenyl)-n'-((1-(4-(dimethylamino)-phenyl)cyclopentyl)methyl)urea hydrochloride |
US11002681B2 (en) * | 2015-12-02 | 2021-05-11 | Indian Institute Of Science | Method for rapid raman spectra detection of a single bacterium or group of bacterial species |
US11446398B2 (en) | 2016-04-11 | 2022-09-20 | Obsidian Therapeutics, Inc. | Regulated biocircuit systems |
CN108078969B (zh) * | 2017-12-25 | 2020-06-30 | 临沂大学 | 萘酰肼类化合物在制备抗微生物药物中的用途 |
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JP2707012B2 (ja) * | 1991-12-06 | 1998-01-28 | キッセイ薬品工業株式会社 | N−tert−ブチル−1−メチル−3,3−ジフェニルプロピルアミン塩酸塩の結晶多形およびその製造方法 |
US5530028A (en) | 1992-11-23 | 1996-06-25 | Rohm And Haas Company | Insecticidal N'-substituted-N,N'-diacylhydrazines |
US6057287A (en) | 1994-01-11 | 2000-05-02 | Dyax Corp. | Kallikrein-binding "Kunitz domain" proteins and analogues thereof |
US6267985B1 (en) | 1999-06-30 | 2001-07-31 | Lipocine Inc. | Clear oil-containing pharmaceutical compositions |
US8105825B2 (en) | 2000-10-03 | 2012-01-31 | Intrexon Corporation | Multiple inducible gene regulation system |
US7531326B2 (en) | 2001-02-20 | 2009-05-12 | Intrexon Corporation | Chimeric retinoid X receptors and their use in a novel ecdysone receptor-based inducible gene expression system |
EP1373470B1 (en) | 2001-02-20 | 2013-04-24 | Intrexon Corporation | Novel substitution mutant receptors and their use in a nuclear receptor-based inducible gene expression system |
CA2820170C (en) | 2001-09-26 | 2016-07-05 | Intrexon Corporation | Whitefly ecdysone receptor nucleic acids, polypeptides, and uses thereof |
US7563879B2 (en) | 2001-09-26 | 2009-07-21 | Intrexon Corporation | Leafhopper ecdysone receptor nucleic acids, polypeptides, and uses thereof |
AU2003219965A1 (en) | 2002-03-01 | 2003-09-16 | The Trustees Of Columbia University In The City Of New York | Reagents for asymmetric allylation, aldol, and tandem aldol and allylation reactions |
US7153829B2 (en) | 2002-06-07 | 2006-12-26 | Dyax Corp. | Kallikrein-inhibitor therapies |
US7304161B2 (en) | 2003-02-10 | 2007-12-04 | Intrexon Corporation | Diaclhydrazine ligands for modulating the expression of exogenous genes in mammalian systems via an ecdysone receptor complex |
US7456315B2 (en) * | 2003-02-28 | 2008-11-25 | Intrexon Corporation | Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex |
CA3050564A1 (en) | 2003-08-29 | 2005-03-10 | Dyax Corp. | Poly-pegylated protease inhibitors |
US7935510B2 (en) | 2004-04-30 | 2011-05-03 | Intrexon Corporation | Mutant receptors and their use in a nuclear receptor-based inducible gene expression system |
US7235530B2 (en) | 2004-09-27 | 2007-06-26 | Dyax Corporation | Kallikrein inhibitors and anti-thrombolytic agents and uses thereof |
EP2001500A4 (en) | 2006-03-10 | 2010-07-28 | Dyax Corp | FORMULATIONS FOR ECALLANTIDE |
WO2008153801A1 (en) * | 2007-05-29 | 2008-12-18 | Intrexon Corporation | Chiral diachylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex |
EP2185730A4 (en) * | 2007-08-23 | 2010-10-27 | Intrexon Corp | METHOD AND COMPOSITIONS FOR SICKNESS DIAGNOSIS |
JP2010540534A (ja) * | 2007-09-28 | 2010-12-24 | イントレキソン コーポレーション | 生体治療分子の発現のための治療遺伝子スイッチ構築物およびバイオリアクター、ならびにその使用 |
KR101655487B1 (ko) | 2007-10-08 | 2016-09-08 | 인트렉손 코포레이션 | 가공된 수지상 세포 및 암의 치료를 위한 이의 용도 |
AU2009302804B2 (en) * | 2008-10-08 | 2015-07-02 | Intrexon Corporation | Engineered cells expressing multiple immunomodulators and uses thereof |
CA2848222C (en) * | 2011-09-08 | 2020-06-16 | Intrexon Corporation | Crystalline diacylhydrazine and the use thereof |
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