WO2016024858A1 - Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives - Google Patents

Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives Download PDF

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Publication number
WO2016024858A1
WO2016024858A1 PCT/NL2015/050555 NL2015050555W WO2016024858A1 WO 2016024858 A1 WO2016024858 A1 WO 2016024858A1 NL 2015050555 W NL2015050555 W NL 2015050555W WO 2016024858 A1 WO2016024858 A1 WO 2016024858A1
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WO
WIPO (PCT)
Prior art keywords
formula
compound
process according
acid
preparation
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/NL2015/050555
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English (en)
French (fr)
Inventor
John Ford
Johannes Paulus Gerardus Seerden
Amandine LEDRU
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.)
NewAmsterdam Pharma NV
Original Assignee
Dezima Pharma BV
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=51429345&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2016024858(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to MX2017001930A priority Critical patent/MX367908B/es
Priority to ES15767345T priority patent/ES2926775T3/es
Priority to SM20220385T priority patent/SMT202200385T1/it
Priority to KR1020177006422A priority patent/KR102572626B1/ko
Priority to SG11201701077XA priority patent/SG11201701077XA/en
Priority to SI201531874T priority patent/SI3180314T1/sl
Priority to PL15767345.0T priority patent/PL3180314T3/pl
Priority to EA201790364A priority patent/EA034357B1/ru
Priority to EP15767345.0A priority patent/EP3180314B1/en
Priority to JP2017528754A priority patent/JP6670310B2/ja
Priority to DK15767345.0T priority patent/DK3180314T3/da
Priority to CN201580046606.1A priority patent/CN107108558B/zh
Priority to EP22179712.9A priority patent/EP4083022A1/en
Priority to HRP20221061TT priority patent/HRP20221061T1/hr
Priority to RS20220810A priority patent/RS63575B1/sr
Priority to US15/503,686 priority patent/US10112904B2/en
Priority to CA2958040A priority patent/CA2958040C/en
Priority to LTEPPCT/NL2015/050555T priority patent/LT3180314T/lt
Priority to MA40378A priority patent/MA40378B1/fr
Priority to AU2015302407A priority patent/AU2015302407B2/en
Priority to BR112017002873-5A priority patent/BR112017002873B1/pt
Application filed by Dezima Pharma BV filed Critical Dezima Pharma BV
Publication of WO2016024858A1 publication Critical patent/WO2016024858A1/en
Priority to IL250525A priority patent/IL250525B/en
Anticipated expiration legal-status Critical
Priority to ZA2017/01100A priority patent/ZA201701100B/en
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the Povarov reaction is a 3-component reaction in which a c/s-2-alkyl-4-amino- 1,2,3,4-tetrahydroquinoline is formed in one stereoselective step from an aniline, an aldehyde and an enamine (Tetrahedron 2009, 65, 2721).
  • the use of this reaction has been reported in the literature, however its application in the preparation of
  • step b) of the process of the present invention the compound with formula V is hydrolyzed to form the compound of formula I.
  • hydrolysis is carried out by warming a mixture comprising compound V for 1 to 3 hours at a temperature of 45 to 80°C in the presence of an aqueous acid, preferably hydrochloric acid.
  • reactor B and reactor C were added simultaneously to reactor A over ⁇ 4 hours whilst keeping the temperature of the contents of reactor A at 20-30°C.
  • the reaction mixture in reactor A was stirred at 20-25°C for 16 hours.
  • the mixture was then cooled to 0-5°C and stirred for 3 hours.
  • the precipitate was filtered off and washed with cold acetonitrile (100 ml).
  • the solid was then dried under vacuum at 40°C for 16 hours to give 3 lg of the Povarov product (37% yield).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Obesity (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Quinoline Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PCT/NL2015/050555 2014-08-12 2015-07-29 Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives Ceased WO2016024858A1 (en)

Priority Applications (23)

Application Number Priority Date Filing Date Title
ES15767345T ES2926775T3 (es) 2014-08-12 2015-07-29 Proceso de preparación de intermedios sintéticos para la preparación de derivados de tetrahidroquinolina
EP22179712.9A EP4083022A1 (en) 2014-08-12 2015-07-29 Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives
SM20220385T SMT202200385T1 (it) 2014-08-12 2015-07-29 Processo per la preparazione di composti intermedi sintetici per la preparazione di derivati di tetraidrochinolina
KR1020177006422A KR102572626B1 (ko) 2014-08-12 2015-07-29 테트라하이드로퀴놀린 유도체 제조용의 합성 중간체를 제조하기 위한 방법
SG11201701077XA SG11201701077XA (en) 2014-08-12 2015-07-29 Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives
SI201531874T SI3180314T1 (sl) 2014-08-12 2015-07-29 Postopek za pripravo sintetičnih intermediatov za pripravo derivatov tetrahidrokinolina
PL15767345.0T PL3180314T3 (pl) 2014-08-12 2015-07-29 Sposób wytwarzania syntetycznych związków pośrednich do wytwarzania pochodnych tetrahydrochinoliny
EA201790364A EA034357B1 (ru) 2014-08-12 2015-07-29 Способ получения синтетических промежуточных соединений для получения производных тетрагидрохинолина
EP15767345.0A EP3180314B1 (en) 2014-08-12 2015-07-29 Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives
JP2017528754A JP6670310B2 (ja) 2014-08-12 2015-07-29 テトラヒドロキノリン誘導体の調製のための合成中間体の調製方法
DK15767345.0T DK3180314T3 (da) 2014-08-12 2015-07-29 Fremgangsmåde til fremstilling af syntetiske mellemprodukter til fremstilling af tetrahydroquinolin-derivater
RS20220810A RS63575B1 (sr) 2014-08-12 2015-07-29 Postupak za pripremu sintetičkih intermedijera za pripremu tetrahidrohinolinskih derivata
HRP20221061TT HRP20221061T1 (hr) 2014-08-12 2015-07-29 Postupak za pripremu sintetičkih intermedijera za pripremu tetrahidrokinolinskih derivata
MX2017001930A MX367908B (es) 2014-08-12 2015-07-29 Proceso para preparar intermediarios sinteticos para preparar derivados de tetrahidroquinolina.
CN201580046606.1A CN107108558B (zh) 2014-08-12 2015-07-29 制备用于制备四氢喹啉衍生物的合成中间体的方法
US15/503,686 US10112904B2 (en) 2014-08-12 2015-07-29 Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives
CA2958040A CA2958040C (en) 2014-08-12 2015-07-29 Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives
LTEPPCT/NL2015/050555T LT3180314T (lt) 2014-08-12 2015-07-29 Sintetinių tarpinių junginių, skirtų tetrahidrochinolino darinių gamybai, gavimo būdas
MA40378A MA40378B1 (fr) 2014-08-12 2015-07-29 Procédé de préparation d'intermédiaires synthétiques pour la préparation de dérivés de la tétrahydroquinoléine
AU2015302407A AU2015302407B2 (en) 2014-08-12 2015-07-29 Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives
BR112017002873-5A BR112017002873B1 (pt) 2014-08-12 2015-07-29 Processo para preparar intermediários sintéticos para preparar derivados de tetra-hidroquinolina
IL250525A IL250525B (en) 2014-08-12 2017-02-09 Process for the preparation of synthetic intermediates for the preparation of tetrahydroquinoline derivatives
ZA2017/01100A ZA201701100B (en) 2014-08-12 2017-02-14 Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NL2014050556 2014-08-12
NLPCT/NL2014/050556 2014-08-12

Publications (1)

Publication Number Publication Date
WO2016024858A1 true WO2016024858A1 (en) 2016-02-18

Family

ID=51429345

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/NL2015/050555 Ceased WO2016024858A1 (en) 2014-08-12 2015-07-29 Process for preparing synthetic intermediates for preparing tetrahydroquinoline derivatives

Country Status (27)

Country Link
US (1) US10112904B2 (enExample)
EP (2) EP4083022A1 (enExample)
JP (1) JP6670310B2 (enExample)
KR (1) KR102572626B1 (enExample)
CN (1) CN107108558B (enExample)
AR (1) AR101509A1 (enExample)
AU (1) AU2015302407B2 (enExample)
BR (1) BR112017002873B1 (enExample)
CA (1) CA2958040C (enExample)
CL (1) CL2017000367A1 (enExample)
DK (1) DK3180314T3 (enExample)
EA (1) EA034357B1 (enExample)
ES (1) ES2926775T3 (enExample)
HR (1) HRP20221061T1 (enExample)
HU (1) HUE059947T2 (enExample)
IL (1) IL250525B (enExample)
LT (1) LT3180314T (enExample)
MA (1) MA40378B1 (enExample)
MX (1) MX367908B (enExample)
PL (1) PL3180314T3 (enExample)
PT (1) PT3180314T (enExample)
RS (1) RS63575B1 (enExample)
SG (1) SG11201701077XA (enExample)
SI (1) SI3180314T1 (enExample)
SM (1) SMT202200385T1 (enExample)
TW (1) TWI691490B (enExample)
WO (1) WO2016024858A1 (enExample)

Cited By (7)

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WO2023129595A1 (en) 2021-12-30 2023-07-06 Newamsterdam Pharma B.V. Obicetrapib and sglt2 inhibitor combination
WO2024009144A1 (en) 2022-07-05 2024-01-11 Newamsterdam Pharma B.V. Salts of obicetrapib and processes for their manufacture and intermediates thereof
WO2024042061A1 (en) 2022-08-22 2024-02-29 Newamsterdam Pharma B.V. Obicetrapib and ezetimibe combination treatment and fixed dose pharmaceutical compositions
WO2024165395A1 (en) 2023-02-07 2024-08-15 Newamsterdam Pharma B.V. Obicetrapib and ezetimibe combination treatment and fixed dose pharmaceutical compositions
WO2025093436A1 (en) 2023-11-01 2025-05-08 Newamsterdam Pharma B.V. Treatment and prevention of age-related macular degeneration using a cetp inhibitor
WO2025146262A1 (en) 2024-01-03 2025-07-10 Newamsterdam Pharma B.V. Obicetrapib for use in the treatment of hemoglobinopathies
WO2025146415A1 (en) 2024-01-03 2025-07-10 Newamsterdam Pharma B.V. Improvement in atherosclerotic plaque characteristics with obicetrapib

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CA3212483A1 (en) 2021-03-05 2022-09-09 Newamsterdam Pharma B.V. Obicetrapib for treatment of dementias
CN117940125A (zh) 2021-07-26 2024-04-26 新阿姆斯特丹制药私人有限公司 His弱应答者的治疗
WO2025059594A1 (en) 2023-09-15 2025-03-20 Newamsterdam Pharma B.V. METHODS FOR TREATING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HeFH)
WO2025093129A1 (en) 2023-11-01 2025-05-08 Newamsterdam Pharma B.V. Treatment and prevention of age-related macular degeneration using a cetp inhibitor

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000017164A1 (en) * 1998-09-17 2000-03-30 Pfizer Products Inc. 4-carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines as cetp inhibitors
WO2007116922A1 (en) 2006-03-30 2007-10-18 Mitsubishi Tanabe Pharma Corporation A process for preparing tetrahydroquinoline derivatives

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ20032898A3 (cs) * 2001-04-30 2004-07-14 Pfizer Products Inc. Způsob výroby inhibitorů CETP
UA90269C2 (ru) * 2004-04-02 2010-04-26 Мицубиси Танабе Фарма Корпорейшн Тетрагидрохинолиновые производные и способ их получения
CN101466679A (zh) * 2006-03-30 2009-06-24 田边三菱制药株式会社 制备四氢喹啉衍生物的方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000017164A1 (en) * 1998-09-17 2000-03-30 Pfizer Products Inc. 4-carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines as cetp inhibitors
WO2007116922A1 (en) 2006-03-30 2007-10-18 Mitsubishi Tanabe Pharma Corporation A process for preparing tetrahydroquinoline derivatives

Non-Patent Citations (27)

* Cited by examiner, † Cited by third party
Title
"Cholesterol Treatment Trialists (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials", LANCET, vol. 13, 2010, pages 1670 - 1681
"The Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk of vascular disease", JAMA, vol. 302, 2009, pages 1993 - 2000
AM ENDE DJ; DEVRIES KM; CLIFFORD PJ; BRENEK SJ: "A Calorimetric Investigation To Safely Scale-Up a Curtius Rearrangement of Acryloyl Azide", ORG PROC RES DEV, vol. 2, 1998, pages 382 - 392
ANA ESCRIBANO ET AL: "Design and synthesis of new tetrahydroquinolines derivatives as CETP inhibitors", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, AMSTERDAM, NL, vol. 22, no. 11, 7 April 2012 (2012-04-07), pages 3671 - 3675, XP028423341, ISSN: 0960-894X, [retrieved on 20120413], DOI: 10.1016/J.BMCL.2012.04.042 *
ANTONIO M. GOTTO JR.: "Evaluation of Lipids, Drug Concentration, and Safety Parameters Following Cessation of Treatment With the Cholesteryl Ester Transfer Protein Inhibitor Anacetrapib in Patients With or at High Risk for Coronary Heart Disease", AM. J. CARDIOL., vol. 113, no. 1, 1 January 2014 (2014-01-01), pages 76 - 83
BARTER PJ; CAULFIELD M; ERIKSSON M ET AL.: "Effects of torcetrapib in patients at high risk for coronary events", NENGL JMED, vol. 357, 2007, pages 21009 - 2122
BARTER PJ; RYE K-A; BELTANGADY MS ET AL.: "Relationship between atorvastatin dose and the harm caused by torcetrapib", J LIPID RES, vol. 53, 2012, pages 2436 - 2442
BLOOMFIELD D; CARLSON GL; ADITI SAPRE BS ET AL.: "Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients", AM HEART J, vol. 157, 2009, pages 352 - 360
DAGOUSSET G; ZHU J; MASSON G: "Chiral Phosphoric Acid-Catalyzed Enantioselective Three-Component Povarov Reaction Using Enecarbamates as Dienophiles: Highly Diastereo- and Enantioselective Synthesis of Substituted 4-Aminotetrahydroquinolines", JAM CHEM SOC., vol. 133, 2011, pages 14804 - 14813
DAMON DB; DUGGER RW; MAGNUS-ARYITEY G; RUGGERI RB; WESTER RT; TU M; ABRAMOV Y: "Synthesis of the CETP Inhibitor Torcetrapib: The Resolution Route and Origin of Stereoselectivity in the Iminium Ion Cyclization", ORG PROC RES DEV., vol. 10, 2006, pages 464 - 471
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; ESCRIBANO, ANA ET AL: "Design and synthesis of new tetrahydroquinolines derivatives as CETP inhibitors", XP002730088, retrieved from STN Database accession no. 2012:630964 *
FORREST MJ; BLOOMFIELD D; BRISCOE RJ ET AL.: "Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increasing circulating levels of aldosterone", BR J PHARMACOL, vol. 154, 2008, pages 1465 - 1473
GOVINDAN CK: "An improved process for the preparation of benzyl-N-vinyl carbamate", ORG PROC RES DEV, vol. 6, 2002, pages 74 - 77
HUANG D; XU F; CHEN T; WANG Y; LIN X: "Highly enantioselective three-component Povarov reaction catalyzed by SPINOL-phosphoric acids", RSC ADVANCES, vol. 3, 2013, pages 573
KASTELEIN JJP; VAN LEUVEN SI; BURGESS L ET AL.: "Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia", N ENGL J MED., vol. 356, 2007, pages 1620 - 1630
KOUZNETSOV ET AL: "Recent synthetic developments in a powerful imino Diels-Alder reaction (Povarov reaction): application to the synthesis of N-polyheterocycles and related alkaloids", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 65, no. 14, 4 April 2009 (2009-04-04), pages 2721 - 2750, XP026001418, ISSN: 0040-4020, [retrieved on 20090303], DOI: 10.1016/J.TET.2008.12.059 *
KRISHNA R; BERGMAN AJ; FALLON ET AL.: "Multiple-dose pharmacodynamics and pharmacokinetics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects", CLIN PHARMACOL THER, vol. 84, 2008, pages 679 - 683
LIISCHER TF; TADDEI S; KASKI JC ET AL.: "Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial", EUR HEART J., vol. 33, 2012, pages 857 - 65
LIU H; DAGOUSSET G; MASSON G; RETAILLEAU P; ZHU J: "Chiral Bronsted Acid-Catalyzed Enantioselective Three-Component Povarov Reaction", JAM CHEM SOC., vol. 131, 2009, pages 4598 - 4599
NICHOLLS SJ; BREWER HB; KASTELEIN JJP ET AL.: "Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol", JAMA, vol. 306, 2011, pages 2099 - 2109
NICHOLLS SJ; TUZCU EM; BRENNAN DM; TARDIF J-C; NISSEN SE: "Cholesteryl ester transfer protein inhibition, high-density lipoprotein raising, and progression of coronary atherosclerosis. Insights from ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation", CIRCULATION, vol. 118, 2008, pages 2506 - 2514
ROGER VL; GO AS; LLOYD-JONES DM ET AL.: "Heart disease and stroke statistics - 2012 Update: A report from the American Heart Association", CIRCULATION, vol. 125, 2012, pages E12 - E230
SCHWARTZ GG; OLSSON AG; ABT M ET AL.: "Effects of dalcetrapib in patients with recent acute coronary syndrome", N ENGL J MED, vol. 367, 2012, pages 2089 - 2099
SIMIC B; HERMANN M; SHAW SG ET AL.: "Torcetrapib impairs endothelial function in hypertension", EUR HEART J, vol. 33, 2012, pages 1615 - 1624
STEIN EA; STROES ES; STEINER G ET AL.: "Safety and tolerability of dalcetrapib", AM J CARDIOL., vol. 104, 2009, pages 82 - 91
TETRAHEDRON, vol. 65, 2009, pages 2721
VERGEER M; BOTS ML; VAN LEUVEN SI; BASART DC; SIJBRANDS EJ; EVANS GW; GROBBEE DE; VISSEREN FL; STALENHOEF AF; STROES ES: "Cholesteryl ester transfer protein inhibitor torcetrapib and off-target toxicity: pooled analysis of the rating atherosclerotic disease change by imaging with a new CETP inhibitor (RADIANCE) trials", CIRCULATION, vol. 118, 2008, pages 2515 - 2522

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023129595A1 (en) 2021-12-30 2023-07-06 Newamsterdam Pharma B.V. Obicetrapib and sglt2 inhibitor combination
WO2024009144A1 (en) 2022-07-05 2024-01-11 Newamsterdam Pharma B.V. Salts of obicetrapib and processes for their manufacture and intermediates thereof
US12006305B2 (en) 2022-07-05 2024-06-11 Newamsterdam Pharma B.V. Salts of obicetrapib and processes for their manufacture and intermediates thereof
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CA2958040A1 (en) 2016-02-18
MA40378A (fr) 2017-06-21
EP4083022A1 (en) 2022-11-02
EA034357B1 (ru) 2020-01-30
JP6670310B2 (ja) 2020-03-18
CA2958040C (en) 2022-09-13
CN107108558A (zh) 2017-08-29
AU2015302407A1 (en) 2017-03-02
JP2017524742A (ja) 2017-08-31
PT3180314T (pt) 2022-09-02
ES2926775T3 (es) 2022-10-28
AU2015302407B2 (en) 2019-09-19
CN107108558B (zh) 2019-11-19
TW201613868A (en) 2016-04-16
PL3180314T3 (pl) 2022-11-21
SMT202200385T1 (it) 2022-11-18
IL250525B (en) 2019-08-29
MA40378B1 (fr) 2022-10-31
HUE059947T2 (hu) 2023-01-28
BR112017002873A8 (pt) 2022-11-08
US20170267640A1 (en) 2017-09-21
LT3180314T (lt) 2022-11-10
SI3180314T1 (sl) 2022-11-30
IL250525A0 (en) 2017-03-30
US10112904B2 (en) 2018-10-30
EA201790364A1 (ru) 2017-07-31
KR20170102204A (ko) 2017-09-08
RS63575B1 (sr) 2022-10-31
SG11201701077XA (en) 2017-03-30
EP3180314A1 (en) 2017-06-21
BR112017002873B1 (pt) 2023-03-28
AR101509A1 (es) 2016-12-21
MX367908B (es) 2019-09-11
TWI691490B (zh) 2020-04-21
EP3180314B1 (en) 2022-06-22
DK3180314T3 (da) 2022-08-29
CL2017000367A1 (es) 2018-02-09
MX2017001930A (es) 2018-03-01
BR112017002873A2 (pt) 2018-07-17

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