[특허]Method for synthesis of reactive conjugate clusters

Method for synthesis of reactive conjugate clusters 원문보기

IPC분류정보
국가/구분	United States(US) Patent 등록
국제특허분류(IPC7판)	C07H-001/00 C07H-003/00 C08B-037/00 A61K-047/48 C07H-015/04 C07H-015/18 C07H-021/00
출원번호	US-0307319 (2015-05-01)
등록번호	US-10098959 (2018-10-16)
국제출원번호	PCT/US2015/028732 (2015-05-01)
국제공개번호	WO2015/168514 (2015-11-05)
발명자 / 주소	Migawa, Michael T. Yu, Jinghua Wan, W. Brad Patel, Satyen P. Vasquez, Guillermo Kinberger, Garth A. Prakash, Thazha P. Seth, Punit P. Swayze, Eric E.
출원인 / 주소	Ionis Pharmaceuticals, Inc.
대리인 / 주소	McNeill Baur PLLC
인용정보	피인용 횟수 : 0 인용 특허 : 108

초록 ▼

Provided herein are improved methods for the synthesis of reactive conjugate clusters and intermediates used in such methods. In particular, improvements are provided that enhance the synthesis of reactive conjugate clusters by reducing the number of synthetic steps required. The reactive conjugate clusters prepared using the improved methods don't include any transacylation impurities that are formed using existing methods. The improved methods also provide an increase in overall yield and a cost benefit over existing methods.

대표청구항 ▼

1. A method for synthesis of a reactive conjugate cluster having the formula: (L-A-N(H)C(═O)-E-)mBg-G-H wherein: L is a ligand having the formula: A is C2 to C10 alkyl optionally interrupted with one or more groups selected from —O—, —N(H)— and C(═O);E is a single bond or C1 to C10 alkyl optionally interrupted with one or more groups selected from —O—, —N(H)— and C(═O);Bg is a branching group having one of the formulas: wherein: each A1 is, independently, CH2, O or N(H); andeach n is, independently, 1 or 2; or G has the formula: —C(═O)—(CH2)j—C(═O)—O—;j is from 1 to 10;m is 3; comprising: reacting a pentafluorophenyl ester protected branching group having the formula: (PFP-O—C(═O)-E-)mBg-G-Pg1 wherein Pg1 is an ester protecting group;with at least 3 equivalents of a functionalized ligand having the formula: L-A-N(H)Pg2 wherein Pg2 is an amino protecting group;in an organic solvent with a palladium catalyst and H2 for a time and under conditions sufficient to provide the reactive conjugate cluster. 2. The method of claim 1 wherein each E is C1 to C4 alkyl. 3. The method of claim 1 wherein each E is a single bond. 4. The method of claim 1 wherein G is —C(═O)—(CH2)3—C(═O)—O—. 5. The method of claim 1 wherein Pg1 is benzyl. 6. The method of claim 1 wherein the pentafluorophenyl ester protected branching group has the formula: 7. The method of claim 1 wherein the pentafluorophenyl ester protected branching group is at least about 95% pure. 8. The method of claim 1 wherein the functionalized ligand has the formula: wherein A is C2 to C10 alkyl optionally interrupted with one or more groups selected from —O—, —N(H)— and C(═O);Pg2 is an amino protecting group. 9. The method of claim 1 wherein the pentafluorophenyl ester protected branching group and about 3.4 equivalents of the functionalized ligand are dissolved in the organic solvent and Pd(OH)2/C is added under H2 with stirring at room temperature until completion. 10. The method of claim 1 wherein the organic solvent is acetonitrile, ethyl acetate, tetrahydrofuran or a mixture thereof. 11. The method of claim 1 wherein the organic solvent is tetrahydrofuran. 12. The method of claim 1 wherein the reactive conjugate cluster is prepared without using column chromatography. 13. The method of claim 1 wherein the reactive conjugate cluster has one of the formulas: 14. A method of preparing a PFP esterified conjugate cluster comprising treatment of the reactive conjugate cluster prepared in claim 1 with pentafluorophenyl trifluoroacetate to provide the PFP esterified conjugate cluster. 15. The method of claim 14 wherein the PFP esterified conjugate cluster is prepared without using column chromatography. 16. The method of claim 14 wherein the PFP esterified conjugate cluster is purified by precipitation. 17. The method of claim 14 wherein the PFP esterified conjugate cluster is prepared by treatment of the reactive conjugate cluster with pentafluorophenyl trifluoroacetate in dichloromethane. 18. The method of claim 14 wherein the PFP esterified conjugate cluster has one of the formulas:

이 특허에 인용된 특허 (108)

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Buhr Chris A. (Daly City CA) Matteucci Mark (Burlingame CA), 2\modified nucleoside and nucleotide compounds.
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Montgomery John A. (Birmingham AL) Secrist ; III John A. (Birmingham AL), 2′-deoxy-4′-thioribonucleosides and their antiviral activity.
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Usman Nassim (Boulder CO) Karpeisky Alexander (Boulder CO) Beigelman Leonid (Longmont CO) Modak Anil (Boulder CO), 2′deoxy-2′-alkylnucleotide containing nucleic acid.
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상세보기
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상세보기
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상세보기
Summerton James E. (Corvallis OR) Weller Dwight D. (Corvallis OR) Stirchak Eugene P. (Corvallis OR), Alpha-morpholino ribonucleoside derivatives and polymers thereof.
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상세보기
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상세보기
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Cook Phillip D. (Carlsbad CA) Sanghvi Yogesh S. (San Marcos CA) Morvan Francois (Montpellier FRX), Backbone modified oligonucleotide analogs and solid phase synthesis thereof.
상세보기
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상세보기
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Teng Kelly (San Diego CA) Sanghvi Yogesh S. (San Marcos CA) Cook Phillip Dan (San Marcos CA), Heteroatomic oligonucleoside linkages.
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Method for synthesis of reactive conjugate clusters 원문보기

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