SK18182000A3 - Kryštalický efavirenz - Google Patents

Kryštalický efavirenz Download PDF

Info

Publication number: SK18182000A3
Authority: SK; Slovakia
Prior art keywords: efavirenz; compound; crystalline; crystalline efavirenz; powder diffraction
Prior art date: 1998-06-11

Application number

SK1818-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Lilian A. Radesca

Michael B. Maurin

Shelley R. Rabel

James R. Moore

Original Assignee

Dupont Pharmaceuticals Company

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.)

1998-06-11

Filing date

1999-06-10

Publication date

2001-08-06

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22214647&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SK18182000(A3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1999-06-10 Application filed by Dupont Pharmaceuticals Company filed Critical Dupont Pharmaceuticals Company

2001-08-06 Publication of SK18182000A3 publication Critical patent/SK18182000A3/sk

Links

XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 title claims abstract description 185
229960003804 efavirenz Drugs 0.000 title claims abstract description 174
XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 title claims abstract description 129
238000000034 method Methods 0.000 claims abstract description 37
238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 36
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
238000000113 differential scanning calorimetry Methods 0.000 claims abstract description 20
239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims abstract description 10
150000001875 compounds Chemical class 0.000 claims description 51
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239000008186 active pharmaceutical agent Substances 0.000 claims description 11
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IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical group CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 115
-1 Efavirenz compound Chemical class 0.000 description 74
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230000000069 prophylactic effect Effects 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
230000005855 radiation Effects 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
230000001177 retroviral effect Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
235000005713 safflower oil Nutrition 0.000 description 1
239000003813 safflower oil Substances 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
229960001852 saquinavir Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000004904 shortening Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000011885 synergistic combination Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
230000008685 targeting Effects 0.000 description 1
BEUUJDAEPJZWHM-COROXYKFSA-N tert-butyl n-[(2s,3s,5r)-3-hydroxy-6-[[(2s)-1-(2-methoxyethylamino)-3-methyl-1-oxobutan-2-yl]amino]-6-oxo-1-phenyl-5-[(2,3,4-trimethoxyphenyl)methyl]hexan-2-yl]carbamate Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)N[C@H](C(=O)NCCOC)C(C)C)CC=1C(=C(OC)C(OC)=CC=1)OC)NC(=O)OC(C)(C)C)C1=CC=CC=C1 BEUUJDAEPJZWHM-COROXYKFSA-N 0.000 description 1
STOSPPMGXZPHKP-UHFFFAOYSA-N tetrachlorohydroquinone Chemical compound OC1=C(Cl)C(Cl)=C(O)C(Cl)=C1Cl STOSPPMGXZPHKP-UHFFFAOYSA-N 0.000 description 1
UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
AAAQKTZKLRYKHR-UHFFFAOYSA-N triphenylmethane Chemical compound C1=CC=CC=C1C(C=1C=CC=CC=1)C1=CC=CC=C1 AAAQKTZKLRYKHR-UHFFFAOYSA-N 0.000 description 1
229950000977 trovirdine Drugs 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
235000012141 vanillin Nutrition 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/18—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 2
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Immunology (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Virology (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Molecular Biology (AREA)
Tropical Medicine & Parasitology (AREA)
AIDS & HIV (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

SK1818-2000A 1998-06-11 1999-06-10 Kryštalický efavirenz SK18182000A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US8898198P	1998-06-11	1998-06-11
PCT/US1999/013199 WO1999064405A1 (en)	1998-06-11	1999-06-10	Crystalline efavirenz

Publications (1)

Publication Number	Publication Date
SK18182000A3 true SK18182000A3 (sk)	2001-08-06

Family

ID=22214647

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1818-2000A SK18182000A3 (sk)	1998-06-11	1999-06-10	Kryštalický efavirenz

Country Status (21)

Country	Link
EP (1)	EP1086087A1 (pl)
JP (1)	JP2002517487A (pl)
CN (1)	CN1307568A (pl)
AR (3)	AR018670A1 (pl)
AU (1)	AU758114C (pl)
BR (1)	BR9911523A (pl)
CA (1)	CA2333550A1 (pl)
EE (1)	EE05547B1 (pl)
HR (1)	HRP990182A2 (pl)
HU (1)	HUP0103819A3 (pl)
IL (1)	IL139793A (pl)
MY (1)	MY126450A (pl)
NO (1)	NO20006255L (pl)
NZ (1)	NZ507713A (pl)
PL (1)	PL198504B1 (pl)
SG (3)	SG111980A1 (pl)
SK (1)	SK18182000A3 (pl)
TW (1)	TWI235152B (pl)
UA (1)	UA74324C2 (pl)
WO (1)	WO1999064405A1 (pl)
ZA (1)	ZA200006173B (pl)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5965729A (en)	1997-02-05	1999-10-12	Merck & Co., Inc.	Process for the crystallization of a reverse transcriptase inhibitor using an anti-solvent
WO2006018853A2 (en)	2004-08-19	2006-02-23	Hetero Drugs Limited	Novel polymorphs of efavirenz
PE20060587A1 (es) *	2004-09-02	2006-07-09	Bristol Myers Squibb Co	Sintesis de (s)-6-cloro-4-ciclopropiletinil-4-trifluorometil-1,4-dihidro-2h-3,1-benzoxazin-2-ona
WO2008108630A1 (en) *	2007-03-02	2008-09-12	Ultimorphix Technologies B.V.	Polymorphic forms of efavirenz
WO2009011567A1 (en) *	2007-07-16	2009-01-22	Ultimorphix Technologies B.V.	Crystalline forms of efavirenz
PL2303267T3 (pl) *	2008-02-04	2013-11-29	Pfizer Ltd	Polimorficzna postać pochodnej [1,2,4]triazolo[4,3-a]pirydyny do leczenia chorób zapalnych
WO2010073254A2 (en)	2008-12-22	2010-07-01	Hetero Research Foundation	Process for preparing efavirenz polymorph
DE102009041443A1 (de)	2009-09-16	2011-03-31	Archimica Gmbh	Salze des 6-Chlor-4-(cyclopropylethinyl)-1,4-dihydro-4-(trifluormethyl)-2H-3,1-benzoxazin-2-ons und deren Synthese, Aufreinigung und Anwendung als Vorstufen für Efavirenz
EP2471783A1 (en)	2010-12-23	2012-07-04	Esteve Química, S.A.	Novel polymorphic form of efavirenz
CN103508973B (zh) *	2012-06-25	2016-04-27	上海迪赛诺药业有限公司	制备依非韦伦i型结晶的方法
CN102924398B (zh) *	2012-11-22	2015-11-18	安徽贝克生物制药有限公司	用于除去依非韦伦对应异构体的方法
WO2014114971A1 (en) *	2013-01-23	2014-07-31	Alienor Farma	Increased dosage of efavirenz for the treatment of cancer
CN105037175B (zh) *	2014-07-18	2017-02-22	盐城迪赛诺制药有限公司	一种用于提高依非韦伦中间体光学纯度的方法
CN105001101B (zh) *	2015-05-28	2017-11-28	乐平市瑞盛制药有限公司	一种4‑氯‑2‑三氟乙酰基苯胺水合物盐酸盐的合成方法
CN108947855B (zh) *	2018-08-10	2021-10-22	江苏沙星化工有限公司	一种依非韦伦关键中间体的合成方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL106507A (en) *	1992-08-07	1997-11-20	Merck & Co Inc	Pharmaceutical compositions containing benzoxazinones and some novel compounds of this type
WO1995020389A1 (en) *	1994-01-28	1995-08-03	Merck & Co., Inc.	Benzoxazinones as inhibitors of hiv reverse transcriptase
US5633405A (en) *	1995-05-25	1997-05-27	Merck & Co., Inc.	Asymmetric synthesis of (-)-6-chloro-4-cyclopropyl-ethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxanzin-2-one
AU3736197A (en) *	1996-07-26	1998-02-20	Du Pont Pharmaceuticals Company	A practical synthesis of benzoxazinones useful as hiv reverse transcripta se inhibitors
DE69724630T2 (de) *	1996-10-02	2004-07-29	Bristol-Myers Squibb Pharma Co.	4,4-disubstituierte 1,4-dihydro-2h-3,1-benzoxazin-2-one die anwendbar sind als hiv-reverstranskriptase-inhibitoren, zwischenprodukte und verfahren zu ihrer herstellung
DE69841972D1 (de) *	1997-02-05	2010-12-09	Merck Sharp & Dohme	Verfahren zur kristallisation eines reverstranskriptase-inhibitors, bei welchem ein anti-lösungsmittel benutzt wird

1999
- 1999-06-08 HR HR60/088,981A patent/HRP990182A2/hr not_active Application Discontinuation
- 1999-06-10 SG SG200207220A patent/SG111980A1/en unknown
- 1999-06-10 PL PL345221A patent/PL198504B1/pl unknown
- 1999-06-10 CN CN99807219A patent/CN1307568A/zh active Pending
- 1999-06-10 BR BR9911523-9A patent/BR9911523A/pt not_active Application Discontinuation
- 1999-06-10 WO PCT/US1999/013199 patent/WO1999064405A1/en not_active Ceased
- 1999-06-10 NZ NZ507713A patent/NZ507713A/en not_active IP Right Cessation
- 1999-06-10 CA CA002333550A patent/CA2333550A1/en not_active Abandoned
- 1999-06-10 AU AU44364/99A patent/AU758114C/en not_active Expired
- 1999-06-10 UA UA2000127048A patent/UA74324C2/uk unknown
- 1999-06-10 SG SG200207221A patent/SG111981A1/en unknown
- 1999-06-10 IL IL139793A patent/IL139793A/en not_active IP Right Cessation
- 1999-06-10 EE EEP200000743A patent/EE05547B1/xx unknown
- 1999-06-10 JP JP2000553414A patent/JP2002517487A/ja active Pending
- 1999-06-10 MY MYPI99002384A patent/MY126450A/en unknown
- 1999-06-10 SG SG200207226-2A patent/SG134977A1/en unknown
- 1999-06-10 EP EP99927468A patent/EP1086087A1/en not_active Withdrawn
- 1999-06-10 HU HU0103819A patent/HUP0103819A3/hu unknown
- 1999-06-10 SK SK1818-2000A patent/SK18182000A3/sk unknown
- 1999-06-11 AR ARP990102809A patent/AR018670A1/es not_active Application Discontinuation
- 1999-07-03 TW TW088109817A patent/TWI235152B/zh not_active IP Right Cessation
2000
- 2000-10-31 ZA ZA200006173A patent/ZA200006173B/xx unknown
- 2000-12-08 NO NO20006255A patent/NO20006255L/no not_active Application Discontinuation
2010
- 2010-07-08 AR ARP100102491A patent/AR077469A2/es not_active Application Discontinuation
- 2010-07-08 AR ARP100102490A patent/AR077407A2/es not_active Application Discontinuation

Also Published As

Publication number	Publication date
HUP0103819A2 (hu)	2002-02-28
PL198504B1 (pl)	2008-06-30
SG134977A1 (en)	2007-09-28
EE05547B1 (et)	2012-06-15
NO20006255L (no)	2001-02-12
SG111981A1 (en)	2005-06-29
EE200000743A (et)	2002-10-15
PL345221A1 (en)	2001-12-03
WO1999064405A1 (en)	1999-12-16
MY126450A (en)	2006-10-31
AR077407A2 (es)	2011-08-24
IL139793A (en)	2006-10-31
CA2333550A1 (en)	1999-12-16
ZA200006173B (en)	2001-10-31
JP2002517487A (ja)	2002-06-18
AR018670A1 (es)	2001-11-28
UA74324C2 (uk)	2005-12-15
AU4436499A (en)	1999-12-30
CN1307568A (zh)	2001-08-08
HRP990182A2 (en)	2000-02-29
NO20006255D0 (no)	2000-12-08
EP1086087A1 (en)	2001-03-28
NZ507713A (en)	2003-08-29
IL139793A0 (en)	2002-02-10
TWI235152B (en)	2005-07-01
AU758114B2 (en)	2003-03-13
BR9911523A (pt)	2001-09-18
AU758114C (en)	2003-10-30
AR077469A2 (es)	2011-08-31
HUP0103819A3 (en)	2003-05-28
SG111980A1 (en)	2005-06-29

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KR100612795B1 (ko)	2006-08-17	결정성 에파비렌즈
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ES2351471T3 (es)	2011-02-07	Nueva sal y polimorfo de inhibidores de dpp-iv.
AU758114C (en)	2003-10-30	Crystalline efavirenz
EP2112155A1 (en)	2009-10-28	Hydrogensulfate salt of 2-acetoxy-5-(a-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine and its preparation
PL202845B1 (pl)	2009-07-31	Pochodne sulfonamidowe, zawierające je kompozycje farmaceutyczne i zastosowanie pochodnych sulfonamidowych
JP2014510139A (ja)	2014-04-24	固体形態のｈｉｖ阻害剤
CN117447375A (zh)	2024-01-26	胍类化合物及其制备方法和用途
US6673372B1 (en)	2004-01-06	Crystalline Efavirenz
US6225317B1 (en)	2001-05-01	Crystalline (-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-3,4-dihydro-2(1H)-quinazolinone
KR100886805B1 (ko)	2009-03-05	탁산 유도체 결정 및 그 제조방법
CZ20004417A3 (cs)	2001-05-16	Krystalický Efavirenz
JPH0129766B2 (pl)	1989-06-14
CN101111247A (zh)	2008-01-23	疱疹病毒相关疾病的预防或治疗剂
AU779356B2 (en)	2005-01-20	Novel dipeptide compound and medicinal use thereof
MXPA00012228A (en)	2001-09-07	Crystalline efavirenz
ZA200406027B (en)	2006-06-28	Novel amino acid derivatives method for productionthereof and pharmaceutical compositions comprisin g said derivative
PT93700A (pt)	1990-11-20	Processo para a preparacao de mercapto-acilamino-acidos
JPH11500754A (ja)	1999-01-19	新規化合物および多発性硬化症の処置法
US20020022659A1 (en)	2002-02-21	Crystalline and salt forms of an HIV protease inhibitor
CA3225801A1 (en)	2023-01-26	Synthesis of substituted tricyclic amides and analogues thereof
JP3001975B2 (ja)	2000-01-24	結晶性チアガビン塩酸塩−水和物、その製造方法および用途
TW202214572A (zh)	2022-04-16	經取代之芳基甲基脲、其類似物及晶形的合成及其使用方法
EP4255425A1 (en)	2023-10-11	Imidazole compounds as inhibitors of enpp1
JPH11240896A (ja)	1999-09-07	［（ｓ）−１−［（ｓ）−２−［（トランス−４−アミノシクロヘキシルメチル）カルバモイル］ピロリジン−１−カルボニル］−２−イソプロピルチオ−２−メチルプロピル］カルバミックアシドプロピルエステルの１／２硫酸塩