LV10919B - Combination of a cholesterol biosynthesis inhibitor and a beta-lactam cholesterol absorption inhibitor - Google Patents
Combination of a cholesterol biosynthesis inhibitor and a beta-lactam cholesterol absorption inhibitor Download PDFInfo
- Publication number
- LV10919B LV10919B LVP-95-189A LV950189A LV10919B LV 10919 B LV10919 B LV 10919B LV 950189 A LV950189 A LV 950189A LV 10919 B LV10919 B LV 10919B
- Authority
- LV
- Latvia
- Prior art keywords
- cholesterol
- lower alkyl
- group
- heteroaryl
- inhibitor
- Prior art date
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- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Hematology (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
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- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
Claims (10)
- LV 10919 Izgudrojuma formula 1. β-Laktāma tipa holesterīna absorbcijas inhibitora pielietojums tāda medikamenta ražošanā, kurā tas tiek kombinācijā ar holesterīna biosintēzes inhibitoru izmantots aterosklerozes ārstēšanai vai profilaksei, vai arī holesterīna līmeņa pazemināšanai plazmā.
- 2. Pielietojums pēc punkta 1, kurā β-laktāma tipa holesterīna absorbcijas inhibitors ir savienojums ar kopējo formulu R A R4 kurā: A ir -CH=CH-B; -C=C-B; •(CH2)p-X-Bf kur p ir 0,1 vai 2 un X ir saite, -NH- vai -S(O)0-2-; 1 heteroarilgrupa, ar benzola gredzenu sametināta heteroarilgrupa, heteroarilgrupa vai ar benzola gredzenu sametināta heteroarilgrupa, kas aizvietota ar W, kurās heteroarilgrupa ir viena no šādām grupām: pirolilgrupa, piridinilgrupa, pirimidinilgrupa, pirazinilgrupa, triazinilgrupa, imidazolilgrupa, tiazolilgrupa, pirazolilgrupa, tienilgrupa, oksazolilgrupa un furanilgrupa, kā ari slāpekli saturošo heteroarilgrupu N-oksīdi, kur W ir 1-3 aizvietotāji pie gredzena oglekļa atomiem, kas ņemti no grupas: zemākā alkilgrupa, ar hidroksilgrupu aizvietota zemākā alkilgrupa, zemākā alkoksigrupa, alkoksialkilgrupa, alkoksialkoksigrupa, alkoksikarbonil-alkoksigrupa, ar zemāko alkoksiiminogrupu aizvietota zemākā alkilgrupa, zemākā alkāndioilgrupa, ar zemāko alkilgrupu aizvietota zemākā alkāndioil-grupa, alliloksigrupa, -CF3, -OCF3, benzilgrupa, R14-benzilgrupa, benziloksi-grupa, R14-benziloksigrupa, fenoksigrupa, R14-fenoksigrupa, dioksolanilgrupa, -N02, -NR10R11f NR^R^zemākā alkilgrupa)-, NR^R^(zemākā alkoksigrupa)--OH, halogēna atoms, -NHC(0)0R5, -NHC(0)R5, R602SNH-, (R602S)2N-, -S(0)2NH2, -S(O)0.2R10, terc-butildimetilsililoksimetilgrupa, -C(0)R12 un grupa -CH2-n R13 pie kam heteroarilgrupu aizvietotāji pie gredzena slāpekļa atomiem, ja tādi ir, ņemti no grupas: zemākā alkilgrupa, zemākā alkoksigrupa, -C(0)0R5, -C(0)R5, -OH, NR10Rļ^zemākā alkilgrupa)-, NR10Rn(zemākā alkoksigrupa)-, -S(0)2NH2 un 2-(trimetilsilil)etoksimetilgrupa; -C(0)-B; vai /—^ grupa KCH2)k" kur k ir 1 vai 2; D ir B’-(CH2)mC(0)-, kur m ir 1,2, 3, 4 vai 5; B’-(CH2)q-, kur q ir 2, 3, 4, 5 vai 6; 2 LV 10919 B’-(CH2)e-Z-(CH2)r-> kur Z ir -0-, -C(O)-, fenilēngrupa, -NR8- vai .5(0)0 2-, e ir 0, 1, 2, 3, 4 vai 5 un r ir 1,2, 3, 4 vai 5, ar tādu noteikumu, ka e un r summa ir 1,2, 3, 4, 5 vai 6; B’-(C2.6-alkenilēngrupa)-; B’-(C4.6-alkadienilēngrupa)-; B’-(CH2)t-Z-(C2-6-alkenilēngrupa)-, kur Z ir jau minēto nozīmi, bet t ir 0,1, 2 vai 3, ar tādu noteikumu, ka t un alkenilēngrupas virkne kopā satur 2, 3, 4, 5 vai 6 oglekļa atomus; B’-(CH2),-V-(CH2)g-, kur V ir C3.6.cikloalkilēngrupa, f ir 1, 2, 3, 4 vai 5 un g ir 0, 1, 2, 3, 4 vai 5, ar tādu noteikumu, ka f un g summa ir 1, 2, 3, 4, 5 vai 6; B’-(CH2),-V-(C2.6-alkenilēngrupa)- vai B’-(C2.6-alkenilēngrupa)-V-(CH2), , kur V un t nozīmes ir jau minētās, ar tādu noteikumu, ka t un alkenilēngrupas virkne kopā satur 2, 3, 4, 5 vai 6 oglekļa atomus; BXCH2)a-Z-(CH2)b-V-(CH2)d-, kur Z un V nozīmes ir jau minētās, bet a, b un d, neatkarīgi viens no otra, ir 0, 1, 2, 3, 4, 5 vai 6, ar tādu noteikumu, ka a, b un d summa ir 0, 1,2, 3, 4, 5 vai 6; T-(CH2)s-, kur T C3.6.cikloalkilgrupa un s ir 1, 2, 3, 4, 5 vai 6; vai naftilmetilgrupa, heteroarilmetilgrupa, ar W aizvietota heteroarilgrupa, kur heteroarilgrupas un W nozīmes ir jau minētās; p. B ir grupa r3 B’ ir naftilgrupa, heteroarilgrupa, ar W aizvietota heteroarilgrupa, kur heteroarilgrupas un W nozīmes ir jau minētās, vai ari grupaR ir ūdeņraža atoms, fluora atoms, C^^-alkilgrupa, Cļ.^-alkenilgrupa, Cļ.ļs-alkinilgrupa, vai grupa B-(CH2)h-, kur h ir 0,1,2 vai 3; 3 R,, R2 un R3, neatkarīgi viens no otra, ņemti no grupas, kurā ietilpst -H un W, ar tādu noteikumu, ka, ja W ir halogēna atoms, tas ir o- vai m-stāvoklī; vai arī R, ir ūdeņraža atoms, bet R2 un R3 kopā ar tiem blakusesošajiem oglekļa atomiem, pie kuriem tie saistīti, veido dioksolāna ciklu; R/ ,R2’ un R3’ , neatkarīgi viens no otra, ņemti no grupas, kurā ietilpst H un W; vai arī R/ ir ūdeņraža atoms, bet R2’ un R3’ kopā ar tiem blakusesošajiem oglekļa atomiem, pie kuriem tie saistīti, veido dioksolāna ciklu; R4 ir grupa _jy R7)n kurā n ir 0, 1, 2, vai 3, indanilgrupa, benzofuranilgrupa, benzodioksolilgrupa, tetrahidronaftilgrupa, piridinilgrupa, pirazinilgrupa, pirimidinilgrupa, hinolinilgrupa; R5 ir zemākā alkilgrupa, fenilgrupa, R14-fenilgrupa, benzilgrupa, R14-benzilgrupa; R6 ir -OH, zemākā alkilgrupa, fenilgrupa, benzilgrupa, R14-fenilgrupa, R14-benzilgrupa; R7 ir zemākā alkilgrupa, zemākā alkoksigrupa, -OH, halogēna atoms, -NR^Rn, -NHC(0)0R5, -NHC(0)R5, N02i -CN, -N3, -SH, -S(O)0.2-(zemākā alkilgrupa), -COOR9, -CONR^Rn, -COR12, fenoksigrupa, benziloksigrupa, -OCF3 vai terc-butildimetilsililoksigrupa, kur n ir 2 vai 3 un grupas R7 var būt vienādas vai dažādas; R8 ir H, zemākā alkilgrupa, ar fenilgrupu aizvietota zemākā alkilgrupa, vai -C(0)Rg; R9 ir H, zemākā alkilgrupa, fenilgrupa, ar fenilgrupu aizvietota zemākā alkilgrupa; R10 un Rn ir, neatkarīgi viens no otra, ņemti no grupas: H, zemākā alkilgrupa; R12 ir H, -OH, alkoksigrupa, -NR10Rn , grupa -N Rl3 4 LV 10919 fenilgrupa, fenoksigrupa, zemākā alkilgrupa, benziloksigrupa, R14-fenilgrupa; R13 ir -O-, -CH2-, -NH- vai -Nfzemākā alkilgrupa)-; un R14 ir1-3 grupas, kas, neatkarīgi viena no otras, ņemtas no grupas, kurā ietilpst: zemākā alkilgrupa, zemākā alkoksigrupa, -COOH, -N02, -NR10R11, -OH vai halogēna atoms; vai minētā savienojuma farmaceitiski pieņemamās sālis.
- 3. Pielietojums pēc punkta 2 kur β-laktāma tipa holesterīna absorbcijas inhibitors ir (3R,4S)-1,4-bis(4-metoksifenil)-3-(3-fenilpropil)-2-azetidinons.
- 4. Pielietojums pēc punkta 1 kurā holesterīna biosintēzes inhibitors ir ņemts no grupas, kurā ietilpst: HMG KoA reduktāzes inhibitori, skvalēna sintēzes inhibitori un skvalēna epoksidāzes inhibitori.
- 5. Pielietojums pēc punkta 4, kurā holesterīna biosintēzes inhibitors ir ņemts no grupas, kurā ietilpst: lovastatīns, pravastatīns, fluvastatīns, simvastatīns, CI-981, L-659,699, skvalestatīns 1 un NB-598.
- 6. Farmaceitiskā_kompozīcija aterosklerozes ārstēšanai vai profilaksei, vai ari holesterīna līmeņa pazemināšanai plazmā, kas satur β-laktāma tipa holesterīna absorbcijas inhibitoru, holesterīna biosintēzes inhibitoru un farmaceitiski pieņemamu nesēju.
- 7. Farmaceitiskā kompozīcija pēc punkta 6, kurā holesterīna absorbcijas inhibitors ir tāds, kā definēts punktā 4 vai punktā 5.
- 8. Farmaceitiskā kompozīcija pēc punkta 6 vai punkta 7, kurā β-laktāma tipa holesterīna absorbcijas inhibitors ir tāds, kā raksturots punktos 2 vai 3.
- 9. Komplekts ar diviem atsevišķiem farmaceitisko kompozīciju konteineriem vienā iesaiņojumā kombinētai pielietošanai aterosklerozes ārstēšanā vai profilaksē vai arī holesterīna līmeņa pazemināšanai plazmā, kas vienā konteinerā satur efektīvu daudzumu holesterīna biosintēzes inhibitora farmaceitiski pieņemamā nesējā, un otrā konteinerā satur efektīvu daudzumu β-laktāma tipa holesterīna absorbcijas inhibitora farmaceitiski pieņemamā nesējā.
- 10. Komplekts pēc punkta 16, kas vienā konteinerā satur efektīvu daudzumu tāda holesterīna biosintēzes inhibitora, kāds definēts punktā 4 vai punktā 5 farmaceitiski pieņemamā nesējā, un otrā konteinerā satur efektīvu daudzumu tāda β-laktāma tipa holesterīna absorbcijas inhibitora, kāds aprakstīts punktos 2 vai 3 , farmaceitiski pieņemamā nesējā.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US99548892A | 1992-12-23 | 1992-12-23 | |
PCT/US1993/012291 WO1994014433A1 (en) | 1992-12-23 | 1993-12-21 | COMBINATION OF A CHOLESTEROL BIOSYNTHESIS INHIBITOR AND A β-LACTAM CHOLESTEROL ABSORPTION INHIBITOR |
Publications (2)
Publication Number | Publication Date |
---|---|
LV10919A LV10919A (lv) | 1995-12-20 |
LV10919B true LV10919B (en) | 1996-04-20 |
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Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
LVP-95-189A LV10919B (en) | 1992-12-23 | 1995-06-22 | Combination of a cholesterol biosynthesis inhibitor and a beta-lactam cholesterol absorption inhibitor |
Country Status (32)
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US (1) | US5661145A (lv) |
EP (1) | EP0675714B1 (lv) |
JP (1) | JP3992728B2 (lv) |
KR (1) | KR100306936B1 (lv) |
CN (1) | CN1090479C (lv) |
AT (1) | ATE175872T1 (lv) |
AU (1) | AU680864B2 (lv) |
CA (1) | CA2152351C (lv) |
CZ (1) | CZ287125B6 (lv) |
DE (1) | DE69323213T2 (lv) |
DK (1) | DK0675714T3 (lv) |
EE (1) | EE03383B1 (lv) |
ES (1) | ES2128552T3 (lv) |
FI (1) | FI952916A (lv) |
GR (1) | GR3029405T3 (lv) |
HR (1) | HRP931515B1 (lv) |
HU (1) | HU221724B1 (lv) |
IL (1) | IL108112A (lv) |
LT (1) | LT3300B (lv) |
LV (1) | LV10919B (lv) |
MX (1) | MX9308053A (lv) |
MY (1) | MY109538A (lv) |
NO (1) | NO311325B1 (lv) |
NZ (1) | NZ259790A (lv) |
PL (1) | PL174128B1 (lv) |
SG (1) | SG45147A1 (lv) |
SI (1) | SI9300677A (lv) |
SK (1) | SK281173B6 (lv) |
TW (1) | TW319698B (lv) |
WO (1) | WO1994014433A1 (lv) |
YU (1) | YU49060B (lv) |
ZA (1) | ZA939552B (lv) |
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US4680391A (en) * | 1983-12-01 | 1987-07-14 | Merck & Co., Inc. | Substituted azetidinones as anti-inflammatory and antidegenerative agents |
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