ZA200303694B - Sugar-substituted 2-azetidinones useful as hypocholesterolemic agents. - Google Patents

Sugar-substituted 2-azetidinones useful as hypocholesterolemic agents. Download PDF

Info

Publication number: ZA200303694B
Authority: ZA; South Africa
Prior art keywords: alkyl; compound; group; composition; substance
Prior art date: 2000-12-20

Application number

ZA200303694A

Other languages

English (en)

Inventor

Anima Ghosal

Shmuel Zbaida

Swapan K Chowdhury

Robert M Iannucci

Wenqing Feng

Kevin B Alton

James E Patrick

Harry R Davis

Original Assignee

Schering Corp

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.)

2000-12-20

Filing date

2003-05-13

Publication date

2004-08-13

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22973953&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ZA200303694(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2003-05-13 Application filed by Schering Corp filed Critical Schering Corp

2004-08-13 Publication of ZA200303694B publication Critical patent/ZA200303694B/en

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MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 title claims description 29
239000003529 anticholesteremic agent Substances 0.000 title description 6
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 184
150000001875 compounds Chemical class 0.000 claims description 101
125000000217 alkyl group Chemical group 0.000 claims description 81
235000012000 cholesterol Nutrition 0.000 claims description 58
230000015572 biosynthetic process Effects 0.000 claims description 54
239000003112 inhibitor Substances 0.000 claims description 48
238000000034 method Methods 0.000 claims description 41
239000000203 mixture Substances 0.000 claims description 35
-1 iosthiazolyl Chemical group 0.000 claims description 34
125000005843 halogen group Chemical group 0.000 claims description 28
229910052739 hydrogen Inorganic materials 0.000 claims description 28
201000001320 Atherosclerosis Diseases 0.000 claims description 24
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 23
125000003118 aryl group Chemical group 0.000 claims description 21
230000002265 prevention Effects 0.000 claims description 21
125000001424 substituent group Chemical group 0.000 claims description 20
RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 15
230000009467 reduction Effects 0.000 claims description 15
229960002855 simvastatin Drugs 0.000 claims description 15
RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 13
241000124008 Mammalia Species 0.000 claims description 12
239000003937 drug carrier Substances 0.000 claims description 12
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 11
239000008194 pharmaceutical composition Substances 0.000 claims description 11
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 10
XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 8
XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 8
PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 8
TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 8
125000002947 alkylene group Chemical group 0.000 claims description 8
229960005370 atorvastatin Drugs 0.000 claims description 8
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 8
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PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical group C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 8
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 8
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TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 8
KIRGLCXNEVICOG-SOFGYWHQSA-N (e)-n-ethyl-6,6-dimethyl-n-[[3-[(4-thiophen-3-ylthiophen-2-yl)methoxy]phenyl]methyl]hept-2-en-4-yn-1-amine Chemical compound CC(C)(C)C#C/C=C/CN(CC)CC1=CC=CC(OCC=2SC=C(C=2)C2=CSC=C2)=C1 KIRGLCXNEVICOG-SOFGYWHQSA-N 0.000 claims description 7
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ODCZJZWSXPVLAW-KXCGKLMDSA-N Hymeglusin Chemical compound OC(=O)/C=C(\C)/C=C(C)/C[C@H](C)CCCC[C@H]1OC(=O)[C@@H]1CO ODCZJZWSXPVLAW-KXCGKLMDSA-N 0.000 claims description 7
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VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 7
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DFKDOZMCHOGOBR-NCSQYGPNSA-N zaragozic acid A Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CC[C@]12[C@H](O)[C@H]([C@](O2)(C(O)=O)[C@@](O)([C@H](O1)C(O)=O)C(O)=O)OC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)C1=CC=CC=C1 DFKDOZMCHOGOBR-NCSQYGPNSA-N 0.000 claims description 7
DFKDOZMCHOGOBR-UHFFFAOYSA-N zaragozic acid A Natural products O1C(C(O)(C(O2)C(O)=O)C(O)=O)(C(O)=O)C(OC(=O)C=CC(C)CC(C)CC)C(O)C21CCC(=C)C(OC(C)=O)C(C)CC1=CC=CC=C1 DFKDOZMCHOGOBR-UHFFFAOYSA-N 0.000 claims description 7
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
125000002541 furyl group Chemical group 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 4
125000000842 isoxazolyl group Chemical group 0.000 claims description 4
125000002757 morpholinyl group Chemical group 0.000 claims description 4
125000003386 piperidinyl group Chemical group 0.000 claims description 4
125000003226 pyrazolyl group Chemical group 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
125000000168 pyrrolyl group Chemical group 0.000 claims description 4
125000000335 thiazolyl group Chemical group 0.000 claims description 4
125000001544 thienyl group Chemical group 0.000 claims description 4
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
239000005977 Ethylene Substances 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
229910006069 SO3H Inorganic materials 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
239000000460 chlorine Substances 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
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RHGYHLPFVJEAOC-FFNUKLMVSA-L pitavastatin calcium Chemical compound [Ca+2].[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1.[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 RHGYHLPFVJEAOC-FFNUKLMVSA-L 0.000 claims description 3
125000003003 spiro group Chemical group 0.000 claims description 3
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125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 2
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NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 15
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ZA200303694A 2000-12-20 2003-05-13 Sugar-substituted 2-azetidinones useful as hypocholesterolemic agents. ZA200303694B (en)

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US7071181B2 (en)	2001-01-26	2006-07-04	Schering Corporation	Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors
PT1355644E (pt)	2001-01-26	2006-11-30	Schering Corp	Utilização de compostos azetidinona substituídos para o tratamento de sitosterolemia
RS20100015A (sr)	2001-01-26	2010-12-31	Schering Corporation	Kombinacija aktivatora receptora aktiviranog peroksizom- proliferatorom (ppar) fenofibrata sa inhibitorom apsorpcije sterola ezetimibom za vaskularne indikacije
IL157552A0 (en)	2001-03-28	2004-03-28	Schering Corp	Enantioselective synthesis of azetidinone intermediate compounds
EP1429756B1 (en)	2001-09-21	2006-11-22	Schering Corporation	Treatment of xanthoma with azetidinone derivatives as sterol absorption inhibitors
US7056906B2 (en)	2001-09-21	2006-06-06	Schering Corporation	Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women
US7053080B2 (en)	2001-09-21	2006-05-30	Schering Corporation	Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors
GB0215579D0 (en) *	2002-07-05	2002-08-14	Astrazeneca Ab	Chemical compounds
AR040588A1 (es)	2002-07-26	2005-04-13	Schering Corp	Formulacion farmaceutica que comprende un inhibidor de la absorcion del colesterol y un inhibidor de una hmg- co a reductasa
JP2006508188A (ja)	2002-11-06	2006-03-09	シェーリング　コーポレイション	脱髄の処置のためのコレステロール吸収インヒビター
DE602004016123D1 (de)	2003-03-07	2008-10-09	Schering Corp	Substituierte azetidinon-derivate, deren pharmazeutische formulierungen und deren verwendung zur behandlung von hypercholesterolemia
CN1756755A (zh)	2003-03-07	2006-04-05	先灵公司	取代的2－吖丁啶酮化合物、其制剂及其治疗高胆甾醇血症的用途
US7459442B2 (en)	2003-03-07	2008-12-02	Schering Corporation	Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
CN1756756A (zh)	2003-03-07	2006-04-05	先灵公司	取代的2－吖丁啶酮化合物、其制剂及其治疗高胆甾醇血症的用途
JP2005015434A (ja) *	2003-06-27	2005-01-20	Kotobuki Seiyaku Kk	血清コレステロール低下剤或はアテローム性硬化症の予防又は治療剤
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2001
- 2001-12-17 DE DE60106489T patent/DE60106489T2/de not_active Expired - Lifetime
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Also Published As

Publication number	Publication date
CN1483039A (zh)	2004-03-17
KR20030063414A (ko)	2003-07-28
AU3104902A (en)	2002-07-01
HUP0302269A3 (en)	2009-08-28
EP1347987A1 (en)	2003-10-01
TWI316942B (en)	2009-11-11
SI1347987T1 (en)	2005-02-28
MA26975A1 (fr)	2004-12-20
JP2004516299A (ja)	2004-06-03
NO20083737L (no)	2003-08-19
PE20020718A1 (es)	2002-08-09
JP4351842B2 (ja)	2009-10-28
SK286703B6 (sk)	2009-03-05
GEP20053548B (en)	2005-06-27
CZ20031674A3 (cs)	2003-10-15
RU2297422C2 (ru)	2007-04-20
WO2002050090A1 (en)	2002-06-27
AU2002231049B2 (en)	2006-07-20
DE60106489T2 (de)	2005-10-13
CY1106912T1 (el)	2012-09-26
DE60106489D1 (de)	2004-11-18
NO326981B1 (no)	2009-03-30
PT1593670E (pt)	2007-11-08
CA2432798C (en)	2007-02-27
ATE369334T1 (de)	2007-08-15
RU2003122520A (ru)	2005-02-27
KR100883461B1 (ko)	2009-02-16
DE60129863T2 (de)	2008-04-30
MY129148A (en)	2007-03-30
BR0116212A (pt)	2003-12-30
DK1593670T3 (da)	2007-11-05
EP1347987B1 (en)	2004-10-13
NZ525722A (en)	2004-11-26
HK1084945A1 (en)	2006-08-11
JP2009132745A (ja)	2009-06-18
DK1347987T3 (da)	2005-01-31
NO20032806L (no)	2003-08-19
IL155771A0 (en)	2003-12-23
ES2287826T3 (es)	2007-12-16
WO2002050090A8 (en)	2004-04-15
PL363237A1 (en)	2004-11-15
HUP0302269A2 (hu)	2003-10-28
CN100475829C (zh)	2009-04-08
SK7702003A3 (en)	2003-10-07
PL208242B1 (pl)	2011-04-29
ATE279425T1 (de)	2004-10-15
CA2432798A1 (en)	2002-06-27
MXPA03005671A (es)	2003-10-06
HK1056735A1 (en)	2004-02-27
PT1347987E (pt)	2005-01-31
NO20032806D0 (no)	2003-06-19
US20020137690A1 (en)	2002-09-26
DE60129863D1 (de)	2007-09-20
AR035611A1 (es)	2004-06-16
TR200402758T4 (tr)	2004-11-22
ES2230385T3 (es)	2005-05-01
ECSP034659A (es)	2003-07-25
CZ302193B6 (cs)	2010-12-08
SI1593670T1 (sl)	2007-12-31

Publication	Publication Date	Title
EP1347987B1 (en)	2004-10-13	Sugar-substituted 2-azetidinones useful as hypocholesterolemic agents
CA2235943C (en)	2002-10-01	Sugar-substituted 2-azetidinones useful as hypocholesterolemic agents
US5756470A (en)	1998-05-26	Sugar-substituted 2-azetidinones useful as hypocholesterolemic agents
US20030105028A1 (en)	2003-06-05	Substituted 2-azetidinones useful as hypocholesterolemic agents
CZ36599A3 (cs)	1999-06-16	Sloučeniny kyseliny neuraminové
EP1593670B1 (en)	2007-08-08	Hydroxy-substituted 2-azetidinones useful as hypocholesterolemic agents
EP1510521A1 (en)	2005-03-02	Sugar-substituted 2-Azetidinones useful as hypocholesterolemic agents
HK1073315A (en)	2005-09-30	Sugar-substituted 2-azetidinones useful as hypocholesterolemic agents
HK1056735B (en)	2005-05-06	Sugar-substituted 2-azetidinones useful as hypocholesterolemic agents
HK1084945B (en)	2008-01-04	Hydroxy-substituted 2-azetidinones useful as hypocholesterolemic agents
HK1012507B (en)	2002-10-18	Sugar-substituted, 2-azetidinones useful as hypocholesterolemic a gents