ZA200109691B - Mutual prodrugs of amlodipine and atorvastatin. - Google Patents

Mutual prodrugs of amlodipine and atorvastatin. Download PDF

Info

Publication number: ZA200109691B
Authority: ZA; South Africa
Prior art keywords: pharmaceutically acceptable; compound; acceptable salt; mammal; pharmaceutical composition
Prior art date: 1999-05-27

Application number

ZA200109691A

Other languages

English (en)

Inventor

George Chang

Hamanaka Ernest Seiichi

Lamattina John Lawrence

Original Assignee

Pfizer Prod Inc

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.)

1999-05-27

Filing date

2001-11-26

Publication date

2002-11-26

2001-11-26 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2002-11-26 Publication of ZA200109691B publication Critical patent/ZA200109691B/en

Links

229960000528 amlodipine Drugs 0.000 title claims description 59
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 title claims description 53
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 title claims description 53
229960005370 atorvastatin Drugs 0.000 title claims description 53
239000000651 prodrug Substances 0.000 title claims description 35
229940002612 prodrug Drugs 0.000 title claims description 35
HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 title claims 6
150000003839 salts Chemical class 0.000 claims description 70
241000124008 Mammalia Species 0.000 claims description 60
150000001875 compounds Chemical class 0.000 claims description 31
239000008194 pharmaceutical composition Substances 0.000 claims description 25
206010002383 Angina Pectoris Diseases 0.000 claims description 23
206010020772 Hypertension Diseases 0.000 claims description 22
230000000747 cardiac effect Effects 0.000 claims description 22
201000001320 Atherosclerosis Diseases 0.000 claims description 19
208000031226 Hyperlipidaemia Diseases 0.000 claims description 18
208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 11
229910052799 carbon Inorganic materials 0.000 claims description 10
125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 10
125000004432 carbon atom Chemical group C* 0.000 claims description 9
239000000203 mixture Substances 0.000 claims description 9
241000282414 Homo sapiens Species 0.000 claims description 7
230000002411 adverse Effects 0.000 claims description 7
239000003085 diluting agent Substances 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
239000003981 vehicle Substances 0.000 claims description 6
210000004351 coronary vessel Anatomy 0.000 claims description 5
230000002093 peripheral effect Effects 0.000 claims description 5
210000001715 carotid artery Anatomy 0.000 claims description 4
238000001727 in vivo Methods 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 2
150000002148 esters Chemical class 0.000 claims description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical class [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims 1
ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 description 63
238000000034 method Methods 0.000 description 23
208000029078 coronary artery disease Diseases 0.000 description 17
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 description 12
229960004005 amlodipine besylate Drugs 0.000 description 9
229940127291 Calcium channel antagonist Drugs 0.000 description 6
239000000480 calcium channel blocker Substances 0.000 description 6
239000003524 antilipemic agent Substances 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 4
230000000879 anti-atherosclerotic effect Effects 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 4
150000002632 lipids Chemical class 0.000 description 4
OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 description 3
102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 3
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 3
108010028554 LDL Cholesterol Proteins 0.000 description 3
239000002253 acid Substances 0.000 description 3
230000003143 atherosclerotic effect Effects 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
229960001770 atorvastatin calcium Drugs 0.000 description 3
235000012000 cholesterol Nutrition 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
230000002526 effect on cardiovascular system Effects 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
230000002107 myocardial effect Effects 0.000 description 3
229910052760 oxygen Inorganic materials 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
230000000391 smoking effect Effects 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 description 2
102000015779 HDL Lipoproteins Human genes 0.000 description 2
108010010234 HDL Lipoproteins Proteins 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 2
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 description 2
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 description 2
230000002253 anti-ischaemic effect Effects 0.000 description 2
229940030600 antihypertensive agent Drugs 0.000 description 2
239000002220 antihypertensive agent Substances 0.000 description 2
210000001367 artery Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
230000007211 cardiovascular event Effects 0.000 description 2
239000005516 coenzyme A Substances 0.000 description 2
229940093530 coenzyme a Drugs 0.000 description 2
230000034994 death Effects 0.000 description 2
231100000517 death Toxicity 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
230000000694 effects Effects 0.000 description 2
208000031225 myocardial ischemia Diseases 0.000 description 2
229960002965 pravastatin Drugs 0.000 description 2
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 description 2
230000002265 prevention Effects 0.000 description 2
208000037803 restenosis Diseases 0.000 description 2
229960002855 simvastatin Drugs 0.000 description 2
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 description 2
238000001356 surgical procedure Methods 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
XUKUURHRXDUEBC-SVBPBHIXSA-N (3s,5s)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid 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-SVBPBHIXSA-N 0.000 description 1
KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 1
VAYTZRYEBVHVLE-UHFFFAOYSA-N 1,3-dioxol-2-one Chemical class O=C1OC=CO1 VAYTZRYEBVHVLE-UHFFFAOYSA-N 0.000 description 1
GZMPBWRVQSXAJR-UHFFFAOYSA-N 4,5-bis(bromomethyl)-1,3-dioxol-2-one Chemical compound BrCC=1OC(=O)OC=1CBr GZMPBWRVQSXAJR-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
108090000312 Calcium Channels Proteins 0.000 description 1
102000003922 Calcium Channels Human genes 0.000 description 1
208000020446 Cardiac disease Diseases 0.000 description 1
206010007559 Cardiac failure congestive Diseases 0.000 description 1
208000006029 Cardiomegaly Diseases 0.000 description 1
229940127328 Cholesterol Synthesis Inhibitors Drugs 0.000 description 1
KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
208000032928 Dyslipidaemia Diseases 0.000 description 1
208000002705 Glucose Intolerance Diseases 0.000 description 1
206010018429 Glucose tolerance impaired Diseases 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
241000282412 Homo Species 0.000 description 1
208000035150 Hypercholesterolemia Diseases 0.000 description 1
102000004016 L-Type Calcium Channels Human genes 0.000 description 1
108090000420 L-Type Calcium Channels Proteins 0.000 description 1
208000017170 Lipid metabolism disease Diseases 0.000 description 1
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 description 1
208000008589 Obesity Diseases 0.000 description 1
108090000854 Oxidoreductases Proteins 0.000 description 1
102000004316 Oxidoreductases Human genes 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
201000001068 Prinzmetal angina Diseases 0.000 description 1
208000007718 Stable Angina Diseases 0.000 description 1
238000002399 angioplasty Methods 0.000 description 1
FQCKMBLVYCEXJB-MNSAWQCASA-L atorvastatin calcium Chemical compound [Ca+2].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.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 FQCKMBLVYCEXJB-MNSAWQCASA-L 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
229940097320 beta blocking agent Drugs 0.000 description 1
230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
230000008061 calcium-channel-blocking effect Effects 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
239000002327 cardiovascular agent Substances 0.000 description 1
229940125692 cardiovascular agent Drugs 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000011976 chest X-ray Methods 0.000 description 1
235000019504 cigarettes Nutrition 0.000 description 1
RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
208000026758 coronary atherosclerosis Diseases 0.000 description 1
KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
235000001434 dietary modification Nutrition 0.000 description 1
230000000916 dilatatory effect Effects 0.000 description 1
238000002651 drug therapy Methods 0.000 description 1
230000014509 gene expression Effects 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
208000014674 injury Diseases 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
150000002596 lactones Chemical class 0.000 description 1
229940002661 lipitor Drugs 0.000 description 1
230000007774 longterm Effects 0.000 description 1
229960004844 lovastatin Drugs 0.000 description 1
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound 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 description 1
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 description 1
230000007246 mechanism Effects 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
229960001597 nifedipine Drugs 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
238000010606 normalization Methods 0.000 description 1
229940036132 norvasc Drugs 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
230000036581 peripheral resistance Effects 0.000 description 1
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
230000007505 plaque formation Effects 0.000 description 1
230000008569 process Effects 0.000 description 1
230000009696 proliferative response Effects 0.000 description 1
238000009790 rate-determining step (RDS) Methods 0.000 description 1
238000011125 single therapy Methods 0.000 description 1
230000015590 smooth muscle cell migration Effects 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000035488 systolic blood pressure Effects 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
230000008733 trauma Effects 0.000 description 1
239000003643 water by type Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Epidemiology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)

ZA200109691A 1999-05-27 2001-11-26 Mutual prodrugs of amlodipine and atorvastatin. ZA200109691B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US13660899P	1999-05-27	1999-05-27

Publications (1)

Publication Number	Publication Date
ZA200109691B true ZA200109691B (en)	2002-11-26

Family

ID=22473579

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200109691A ZA200109691B (en)	1999-05-27	2001-11-26	Mutual prodrugs of amlodipine and atorvastatin.

Country Status (41)

Country	Link
US (1)	US6486182B1 (ko)
EP (1)	EP1180102B9 (ko)
JP (1)	JP2003500487A (ko)
KR (1)	KR20020012247A (ko)
CN (1)	CN1352640A (ko)
AP (1)	AP2001002345A0 (ko)
AR (1)	AR022344A1 (ko)
AT (1)	ATE268764T1 (ko)
AU (1)	AU3313900A (ko)
BG (1)	BG106149A (ko)
BR (1)	BR0011006A (ko)
CA (1)	CA2375372C (ko)
CO (1)	CO5170457A1 (ko)
CZ (1)	CZ20014229A3 (ko)
DE (1)	DE60011424T2 (ko)
DK (1)	DK1180102T3 (ko)
DZ (1)	DZ3048A1 (ko)
EA (1)	EA200101130A1 (ko)
EE (1)	EE200100631A (ko)
ES (1)	ES2220426T3 (ko)
GT (1)	GT200000078A (ko)
HK (1)	HK1046282A1 (ko)
HN (1)	HN2000000075A (ko)
HR (1)	HRP20010856A2 (ko)
HU (1)	HUP0201433A2 (ko)
IL (1)	IL145947A0 (ko)
IS (1)	IS6135A (ko)
MA (1)	MA26736A1 (ko)
MX (1)	MXPA01012125A (ko)
NO (1)	NO20015756L (ko)
OA (1)	OA11950A (ko)
PA (1)	PA8495701A1 (ko)
PE (1)	PE20010169A1 (ko)
PL (1)	PL353483A1 (ko)
PT (1)	PT1180102E (ko)
SK (1)	SK16792001A3 (ko)
SV (1)	SV2002000082A (ko)
TN (1)	TNSN00113A1 (ko)
TR (1)	TR200103391T2 (ko)
WO (1)	WO2000073298A1 (ko)
ZA (1)	ZA200109691B (ko)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GT199800127A (es) *	1997-08-29	2000-02-01		Combinaciones terapeuticas.
GB0027410D0 (en) *	2000-11-09	2000-12-27	Pfizer Ltd	Mutual prodrug of amlodipine and atorvastatin
US6737430B2 (en)	2000-11-09	2004-05-18	Pfizer, Inc.	Mutual prodrug of amlodipine and atorvastatin
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Also Published As

Publication number	Publication date
MXPA01012125A (es)	2002-06-04
AP2001002345A0 (en)	2001-12-31
TNSN00113A1 (fr)	2005-11-10
NO20015756D0 (no)	2001-11-26
PE20010169A1 (es)	2001-02-10
MA26736A1 (fr)	2004-12-20
DE60011424T2 (de)	2005-08-25
CZ20014229A3 (cs)	2003-01-15
AU3313900A (en)	2000-12-18
HRP20010856A2 (en)	2002-12-31
NO20015756L (no)	2002-01-24
AR022344A1 (es)	2002-09-04
HUP0201433A2 (en)	2002-08-28
OA11950A (en)	2006-04-13
SK16792001A3 (sk)	2003-03-04
WO2000073298A1 (en)	2000-12-07
PA8495701A1 (es)	2001-12-14
US6486182B1 (en)	2002-11-26
BR0011006A (pt)	2002-02-19
HN2000000075A (es)	2001-02-02
CN1352640A (zh)	2002-06-05
KR20020012247A (ko)	2002-02-15
CO5170457A1 (es)	2002-06-27
JP2003500487A (ja)	2003-01-07
IL145947A0 (en)	2002-07-25
BG106149A (en)	2002-05-31
DE60011424D1 (de)	2004-07-15
PL353483A1 (en)	2003-11-17
TR200103391T2 (tr)	2002-04-22
DZ3048A1 (fr)	2004-03-27
SV2002000082A (es)	2002-02-05
GT200000078A (es)	2001-11-16
ES2220426T3 (es)	2004-12-16
CA2375372A1 (en)	2000-12-07
HK1046282A1 (zh)	2003-01-03
ATE268764T1 (de)	2004-06-15
CA2375372C (en)	2007-01-09
EA200101130A1 (ru)	2002-04-25
PT1180102E (pt)	2004-08-31
EP1180102B9 (en)	2005-03-02
DK1180102T3 (da)	2004-09-06
EE200100631A (et)	2003-02-17
IS6135A (is)	2001-10-30
EP1180102B1 (en)	2004-06-09
EP1180102A1 (en)	2002-02-20

Publication	Publication Date	Title
ZA200109693B (en)	2002-11-26	Mutual salt of amlodipine and atorvastatin.
ZA200109691B (en)	2002-11-26	Mutual prodrugs of amlodipine and atorvastatin.
US6455574B1 (en)	2002-09-24	Therapeutic combination
CA2296726C (en)	2004-06-29	Combination therapy
EP1852116A1 (en)	2007-11-07	Pharmaceutical compositions of amlodipine and atorvastatin
US20070149578A1 (en)	2007-06-28	Combination Therapy
US6737430B2 (en)	2004-05-18	Mutual prodrug of amlodipine and atorvastatin
CA2361288C (en)	2007-02-13	Mutual prodrug of amlodipine and atorvastatin