CN110357937A - A kind of Dienogest compound - Google Patents

A kind of Dienogest compound Download PDF

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Publication number
CN110357937A
CN110357937A CN201810260941.7A CN201810260941A CN110357937A CN 110357937 A CN110357937 A CN 110357937A CN 201810260941 A CN201810260941 A CN 201810260941A CN 110357937 A CN110357937 A CN 110357937A
Authority
CN
China
Prior art keywords
dienogest
compound
diene
preparation
diketone
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.)
Pending
Application number
CN201810260941.7A
Other languages
Chinese (zh)
Inventor
丁晓勇
唐四华
聂晓英
李俊杰
耿聪聪
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.)
China Resources Zizhu Pharmaceutical Co Ltd
Original Assignee
China Resources Zizhu Pharmaceutical Co Ltd
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 China Resources Zizhu Pharmaceutical Co Ltd filed Critical China Resources Zizhu Pharmaceutical Co Ltd
Priority to CN201810260941.7A priority Critical patent/CN110357937A/en
Publication of CN110357937A publication Critical patent/CN110357937A/en
Pending legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/18—Feminine contraceptives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0094—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing nitrile radicals, including thiocyanide radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Reproductive Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Endocrinology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Toxicology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides a kind of Dienogest compound, it is characterised in that in 2 θ is to have X-ray diffraction peak at 2 θ characteristic peaks at about 12.1 ± 0.2,15.2 ± 0.2,16.6 ± 0.2,18.4 ± 0.2,18.8 ± 0.2,21.9 ± 0.2,23.1 ± 0.2 and 24.5 ± 0.2.

Description

A kind of Dienogest compound
Technical field
The invention belongs to bulk pharmaceutical chemicals preparation technical fields.More particularly to a kind of Dienogest compound and preparation method thereof.
Technical background
Dienogest, chemical name: -13 Beta-methyl gonane -4,9- diene -3- ketone of -17 beta-hydroxy of 17 alfa-cyanomethyl.Ground promise Pregnant element is a kind of gonane with a variety of hormonal activities and good safety of synthesis.It is a kind of effective progestational hormone, has both few Perhaps female sharp, antiprogestin, antiandrogen and antigonadotrophic activity, but without androgenic activity, it is not in such as acne With the adverse reactions such as seborrhea.
Summary of the invention
An object of the present invention is to provide a kind of Dienogest compound, it is characterised in that 2 θ be about 12.1 ± 0.2, 2 θ at 15.2 ± 0.2,16.6 ± 0.2,18.4 ± 0.2,18.8 ± 0.2,21.9 ± 0.2,23.1 ± 0.2 and 24.5 ± 0.2 There is X-ray diffraction peak at characteristic peak.
Above compound can be used for preparing tablet, capsule, granule, injection and freeze-dried powder.
The second object of the present invention is to provide a kind of pharmaceutical composition, it is characterised in that any containing claim 1-2 Compound and pharmaceutically acceptable auxiliary material described in.
The third object of the present invention is that providing above compound is preparing the application in endometriosis medicine.
The fourth object of the present invention is that providing aforementioned pharmaceutical compositions is preparing answering in endometriosis medicine With.
Above-mentioned compound can often use auxiliary material, injection with pharmaceutically acceptable auxiliary material live vector, such as oral preparation Common auxiliary material etc. together, is prepared into oral preparation such as tablet, capsule, granule, the preparations such as injection such as injection, freeze-dried powder Form.
The fifth object of the present invention is to provide a kind of preparation method of above compound.
Realize the technical solution of the present invention is as follows:
With ring -3- (1,2- ethylene acetal)-female steroid -5 (10), 9 (11)-diene -3,17- diketone (abbreviation 3- ketal) is Raw material carries out 17- addition to 3- ketal with acetonitrile and introduces cyanogen methyl, obtain ring -3- (1,2- ethylidene under n-BuLi catalysis Acetal)-17-17 beta-hydroxies of alfa-cyanomethyl-female steroid-5 (10), 9 (11)-diene-3,17- diketone (abbreviation 17- addition product) is rear to use Glacial acetic acid and perchloric acid slough 3 protecting groups and generate object Dienogest crude product, by being refining to obtain Dienogest.
The invention has the benefit that
The present invention provides a kind of stable Dienogest novel crystal forms, provide better bulk pharmaceutical chemicals for preparation.
Detailed description of the invention
Fig. 1 is the x-ray diffractogram of powder of Dienogest compound of the present invention.
Specific embodiment
Embodiment: the preparation of Dienogest
Ring -3- (1,2- ethylene acetal)-female steroid -5 (10), 9 (11)-diene -3,17- diketone is raw material, in normal-butyl Under lithium catalysis, 17- addition is carried out to 3- ketal with acetonitrile and introduces cyanogen methyl, obtains ring -3- (1,2- ethylene acetal) -17 α-cyanogen first - 17 beta-hydroxies of base-female steroid -5 (10), 9 (11)-diene -3,17- diketone (abbreviation 17- addition product) use glacial acetic acid and perchloric acid afterwards It sloughs 3 protecting groups and generates object Dienogest crude product, acetone recrystallization is refining to obtain finished product.

Claims (5)

1. a kind of Dienogest compound, it is characterised in that 2 θ be about 12.1 ± 0.2,15.2 ± 0.2,16.6 ± 0.2,18.4 There is X-ray diffraction peak at 2 θ characteristic peaks at ± 0.2,18.8 ± 0.2,21.9 ± 0.2,23.1 ± 0.2 and 24.5 ± 0.2.
2. compound according to claim 1, it is characterised in that can be used for preparing tablet, capsule, granule, injection and Freeze-dried powder.
3. a kind of pharmaceutical composition, it is characterised in that can containing the described in any item compounds of claim 1-2 and pharmaceutically connect The auxiliary material received.
4. application of the pharmaceutical composition according to claim 3 in preparation endometriosis, contraceptive.
5. the preparation method of any one of the claim 1-2 compound, it is characterised in that: with ring -3- (1,2- ethylidene contracting Aldehyde)-female steroid -5 (10), 9 (11)-diene -3,17- diketone (abbreviation 3- ketal) is raw material, under n-BuLi catalysis, with acetonitrile 17- addition is carried out to 3- ketal and introduces cyanogen methyl, it is female to obtain -17 beta-hydroxy of ring -3- (1,2- ethylene acetal) -17 alfa-cyanomethyl - Steroid -5 (10), 9 (11)-diene -3,17- diketone (abbreviation 17- addition product), after with glacial acetic acid and perchloric acid slough 3 protecting groups Object Dienogest crude product is generated, by being refining to obtain Dienogest.
CN201810260941.7A 2018-03-26 2018-03-26 A kind of Dienogest compound Pending CN110357937A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810260941.7A CN110357937A (en) 2018-03-26 2018-03-26 A kind of Dienogest compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810260941.7A CN110357937A (en) 2018-03-26 2018-03-26 A kind of Dienogest compound

Publications (1)

Publication Number Publication Date
CN110357937A true CN110357937A (en) 2019-10-22

Family

ID=68213044

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810260941.7A Pending CN110357937A (en) 2018-03-26 2018-03-26 A kind of Dienogest compound

Country Status (1)

Country Link
CN (1) CN110357937A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112209987A (en) * 2020-09-28 2021-01-12 湖南新合新生物医药有限公司 Preparation method of dienogest

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101353365A (en) * 2007-07-23 2009-01-28 天津药业研究院有限公司 Preparation of progestational hormone
CN101360757A (en) * 2005-12-05 2009-02-04 吉瑞工厂 High purity 17alfa-cyanomethyl-17beta-hydroxy-estra-4,9-diene-3-one and process for the synthesis thereof
CN101863947A (en) * 2010-06-29 2010-10-20 沈阳药科大学 Synthesis method of dienogest
CN101993469A (en) * 2009-08-27 2011-03-30 杭州容立医药科技有限公司 Method for preparing medicinal dienogest
CN101993468A (en) * 2009-08-27 2011-03-30 杭州容立医药科技有限公司 Synthesis method for improving dienogest
CN102718828A (en) * 2011-03-30 2012-10-10 西藏海思科药业集团股份有限公司 Preparation method for dienogest
CN102964419A (en) * 2012-12-11 2013-03-13 浙江仙琚制药股份有限公司 Preparation method of compound dienogest
CN103304619A (en) * 2013-06-08 2013-09-18 西藏海思科药业集团股份有限公司 Dienogest compound

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101360757A (en) * 2005-12-05 2009-02-04 吉瑞工厂 High purity 17alfa-cyanomethyl-17beta-hydroxy-estra-4,9-diene-3-one and process for the synthesis thereof
CN101353365A (en) * 2007-07-23 2009-01-28 天津药业研究院有限公司 Preparation of progestational hormone
CN101993469A (en) * 2009-08-27 2011-03-30 杭州容立医药科技有限公司 Method for preparing medicinal dienogest
CN101993468A (en) * 2009-08-27 2011-03-30 杭州容立医药科技有限公司 Synthesis method for improving dienogest
CN101863947A (en) * 2010-06-29 2010-10-20 沈阳药科大学 Synthesis method of dienogest
CN102718828A (en) * 2011-03-30 2012-10-10 西藏海思科药业集团股份有限公司 Preparation method for dienogest
CN102964419A (en) * 2012-12-11 2013-03-13 浙江仙琚制药股份有限公司 Preparation method of compound dienogest
CN103304619A (en) * 2013-06-08 2013-09-18 西藏海思科药业集团股份有限公司 Dienogest compound

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112209987A (en) * 2020-09-28 2021-01-12 湖南新合新生物医药有限公司 Preparation method of dienogest
CN112209987B (en) * 2020-09-28 2021-12-14 湖南新合新生物医药有限公司 Preparation method of dienogest

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Application publication date: 20191022