FI89493C - Förfarande för framställning av terapeutiskt aktiva, fosforhaltiga inh ibitorer av HMG-CoA-reduktas och vid förfarandet användbar ny mellanpr odukt - Google Patents

Förfarande för framställning av terapeutiskt aktiva, fosforhaltiga inh ibitorer av HMG-CoA-reduktas och vid förfarandet användbar ny mellanpr odukt Download PDF

Info

Publication number
FI89493C
FI89493C FI882384A FI882384A FI89493C FI 89493 C FI89493 C FI 89493C FI 882384 A FI882384 A FI 882384A FI 882384 A FI882384 A FI 882384A FI 89493 C FI89493 C FI 89493C
Authority
FI
Finland
Prior art keywords
mmol
acid
lower alkyl
solution
methoxy
Prior art date
Application number
FI882384A
Other languages
English (en)
Finnish (fi)
Other versions
FI882384A (fi
FI89493B (fi
FI882384A0 (fi
Inventor
Donald Steven Karanewsky
Scott Adams Biller
Eric Michael Gordon
Original Assignee
Squibb & Sons 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.)
Filing date
Publication date
Application filed by Squibb & Sons Inc filed Critical Squibb & Sons Inc
Publication of FI882384A0 publication Critical patent/FI882384A0/fi
Publication of FI882384A publication Critical patent/FI882384A/fi
Publication of FI89493B publication Critical patent/FI89493B/fi
Application granted granted Critical
Publication of FI89493C publication Critical patent/FI89493C/sv

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se)
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
    • C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
    • C07F9/32—Esters thereof
    • C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/3211—Esters of acyclic saturated acids which can have further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
    • C07F9/36—Amides thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se)
    • C07F9/3804—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se) not used, see subgroups
    • C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se)
    • C07F9/44—Amides thereof
    • C07F9/4403—Amides thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4407—Amides of acyclic saturated acids which can have further substituents on alkyl

Claims (5)

1. Förfarande för framställning av terapeutiskt aktiva föreningar med formeln 5 O li r-p-ch2-ch-ch2-co2rx X ÖH (CH2)n (I) 10 z i vilken R är OH, nedre alkoxi eller nedre alkyl, X är -O- eller -NH-, 15 n är 1, R \X^vvv/R2 Z är gruppen ^__j J R2a i vilken R1, R2 och R2a kan vara lika eller olika ooh 20 är vardera självständigt H, halogen, nedre alkyl, halo-genalkyl, fenyl, substituerad fenyl eller 0Ry, i vilken Ry är H, alkanoyl, bensoyl, fenyl, halogenfenyl, fenylsubs-tituerad nedre alkyl, nedre alkyl, sinnamyl, halogenalkyl, allyl, cykloalkylsubstituerad nedre alkyl, adamantylsubs-25 tituerad nedre alkyl eller (substituerad fenyl)substituerad nedre alkyl, och R* är väte eller nedre alkyl, samt för framställning av salter därav, känne-t e c k n a t därav, att en silyleter med formeln 30 0 II Rc-P-CH2—CH-CH2-C02alkyl X 0 (VII) ( CH2) Si-C( CH3 )3 1 / \
35. C6H5 C6H5 70 89493 i vilken Rl är nedre alkyl eller nedre alkoxi, spjälkes en silyletergrupp, varvid det bildas en ester med formeln
0 II
5 Rc-P-CH2-CH-CH2-C02Rx X ÖH (VIII) (CH2)n Z (R* är alkyl) 10 och estern förvandlas, om sä önskas, till ett motsvarande salt med formeln O ll
15 R-P-CH2-CH-CH2-C02alkalimetall X OH (CH2)n (VIHA) Z 20. vilken R är nedre alkyl eller nedre alkoxi, till en syra med formeln 0 il R-P-CH2-CH-CH2-C02H
25. OH (CH2)n (VII IB ) i Z till ett motsvarande salt med formeln 30 0 ίΙ aikai imet ai 10-P-CH2-CH-CH2-C02alkalimetall X OH i (CH2)n (VIIIC)
35 Z li 71 89493 eller till en syra med formeln 0 II ho-p-ch2-ch-ch2-co2h
5. OH (VIIID) (CH2)n z
2. Förfarande enligt patentkravet 1, känne-10 tecknat därav, att X är -0- och R är alkoxi.
3. Förfarande enligt patentkravet 1, känne-tecknat därav, att X är -NH- och R är alkoxi.
4. Förfarande enligt patentkravet 1, känne-tecknat därav, att föreningen sorti framställs är
15 S-4-[[[4'-fluor-3,3',5-trimetyl(1,1'-bifenyl)-2-yl]me- toxi]metoxifosfinyl]-3-hydroxibutansyra, metylester eller monolitiumsalt, S—4—[[[4'-fluor-3,3’,5-trimetyl(1,1’-bifenyl)-2-yl]me-toxi]hydroxifosfinyl]-3-hydroxibutansyra, dilitiumsalt, 20 (3S)-4-[[[4’-fluor-3,3’,5-trimetyl(1,1’-bifenyl)-2-yl]- metoxi]metylfosfinyl]-3-hydroxibutansyra, monolitiumsalt, (S)-4-[ [ [2,4-diklor-6-[ (4-fluorfenyl )metoxi] fenyl]metoxi] -metoxifosfinyl]-3-hydroxibutansyra, monolitiumsalt, (3S)-4-[[[2,4-diklor-6-[(4-fluorfenyl)metoxi]fenyl]me-25 toxi]hydroxifosfinyl]-3-hydroxibutansyra, dilitiumsalt, (3S)-4-[[[2,4-diklor-6-[(4-fluorfenyl)metoxi]fenyl]me-toxi]metylfosfinyl]-3-hydroxibutansyra, metylester, eller (S)-4-[[[[4'-fluor-3,3',5-trimetyl(1,1’-bifenyl)-2-yl]-metyl]amino]metoxifosfinyl]-3-hydroxibutansyra, monoli-30 tiumsalt.
5. Mellanprodukt, kännetecknad därav, att den har strukturen 72 8 9 493 o II Ra-P-CH2-CH-CH2-C02alkyl Oalkyl OSi-C(CH3), (IV) c6h5 c6h5 5 i vilken Ra är nedre alkyl, nedre alkoxi eller OH, och vilken struktur innehäller alla stereoisomerer av mellan-produkten. I:
FI882384A 1987-05-22 1988-05-20 Förfarande för framställning av terapeutiskt aktiva, fosforhaltiga inh ibitorer av HMG-CoA-reduktas och vid förfarandet användbar ny mellanpr odukt FI89493C (sv)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US5328187A 1987-05-22 1987-05-22
US5328187 1987-05-22
US10968087A 1987-10-19 1987-10-19
US10968087 1987-10-19

Publications (4)

Publication Number Publication Date
FI882384A0 FI882384A0 (fi) 1988-05-20
FI882384A FI882384A (fi) 1988-11-23
FI89493B FI89493B (fi) 1993-06-30
FI89493C true FI89493C (sv) 1993-10-11

Family

ID=26731667

Family Applications (1)

Application Number Title Priority Date Filing Date
FI882384A FI89493C (sv) 1987-05-22 1988-05-20 Förfarande för framställning av terapeutiskt aktiva, fosforhaltiga inh ibitorer av HMG-CoA-reduktas och vid förfarandet användbar ny mellanpr odukt

Country Status (24)

Country Link
JP (1) JP2680347B2 (sv)
KR (1) KR880013958A (sv)
CN (1) CN88103091A (sv)
AU (1) AU610591B2 (sv)
BE (1) BE1004193A3 (sv)
CH (1) CH676984A5 (sv)
DE (1) DE3817375C2 (sv)
DK (1) DK277488A (sv)
ES (1) ES2009918A6 (sv)
FI (1) FI89493C (sv)
FR (1) FR2615508B1 (sv)
GB (1) GB2205837B (sv)
GR (1) GR1000959B (sv)
HU (1) HU205125B (sv)
IE (2) IE63760B1 (sv)
IL (1) IL86464A (sv)
IT (1) IT1217685B (sv)
NL (1) NL8801330A (sv)
NO (1) NO882218L (sv)
NZ (1) NZ224733A (sv)
PH (1) PH25350A (sv)
PL (1) PL154877B1 (sv)
PT (1) PT87539B (sv)
SE (1) SE503210C2 (sv)

Families Citing this family (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE501541C2 (sv) * 1987-05-22 1995-03-06 Squibb & Sons Inc Fosforhaltiga HMG-CoA reduktasinhibitorer, nya mellanprodukter och metod
CA2007643A1 (en) * 1989-02-01 1990-08-01 Donald S. Karanewsky Combination of an hmg coa reductase inhibitor and a squalene synthetase inhibitor and method for lowering serum cholesterol using such combination
CA2042526A1 (en) * 1990-06-11 1991-12-12 Adeoye Y. Olukotun Method for preventing a second heart attack employing an hmg coa reductase inhibitor
US5202327A (en) * 1991-07-10 1993-04-13 E. R. Squibb & Sons, Inc. Phosphorus-containing hmg-coa reductase inhibitors
GB9126144D0 (en) * 1991-12-10 1992-02-12 British Bio Technology Compounds
US20010006644A1 (en) 1997-07-31 2001-07-05 David J. Bova Combinations of hmg-coa reductase inhibitors and nicotinic acid and methods for treating hyperlipidemia once a day at night
IL141786A0 (en) 1998-09-17 2002-03-10 Bristol Myers Squibb Co A pharmaceutical composition for treating diabetes containing an ap2 inhibitor
ATE318272T1 (de) 2001-04-11 2006-03-15 Bristol Myers Squibb Co Aminosäurekomplexe von c-arylglycosiden zur behandlung von diabetes und verfahren
US7238671B2 (en) 2001-10-18 2007-07-03 Bristol-Myers Squibb Company Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions
KR20040054729A (ko) 2001-10-18 2004-06-25 브리스톨-마이어스 스큅 컴퍼니 인간 글루카곤-유사-펩티드-1 모방체, 및 당뇨병 및 이와관련된 증상의 치료에 있어서 이의 용도
US6806381B2 (en) 2001-11-02 2004-10-19 Bristol-Myers Squibb Company Process for the preparation of aniline-derived thyroid receptor ligands
US7057046B2 (en) 2002-05-20 2006-06-06 Bristol-Myers Squibb Company Lactam glycogen phosphorylase inhibitors and method of use
ES2344057T3 (es) 2002-10-23 2010-08-17 Bristol-Myers Squibb Company Inhibidores de la dipeptidil peptidasa iv basados en nitrilos de glicina.
US7098235B2 (en) 2002-11-14 2006-08-29 Bristol-Myers Squibb Co. Triglyceride and triglyceride-like prodrugs of glycogen phosphorylase inhibiting compounds
TW200504021A (en) 2003-01-24 2005-02-01 Bristol Myers Squibb Co Substituted anilide ligands for the thyroid receptor
US7459474B2 (en) 2003-06-11 2008-12-02 Bristol-Myers Squibb Company Modulators of the glucocorticoid receptor and method
US6995183B2 (en) 2003-08-01 2006-02-07 Bristol Myers Squibb Company Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods
US8158362B2 (en) 2005-03-30 2012-04-17 Decode Genetics Ehf. Methods of diagnosing susceptibility to myocardial infarction and screening for an LTA4H haplotype
WO2005087234A1 (en) 2004-03-05 2005-09-22 The Trustees Of The University Of Pennsylvania Methods for treating disorders or diseases associated with hyperlipidemia and hypercholesterolemia while minimizing side-effects
TW200611704A (en) 2004-07-02 2006-04-16 Bristol Myers Squibb Co Human glucagon-like-peptide-1 modulators and their use in the treatment of diabetes and related conditions
US7145040B2 (en) 2004-07-02 2006-12-05 Bristol-Myers Squibb Co. Process for the preparation of amino acids useful in the preparation of peptide receptor modulators
US7534763B2 (en) 2004-07-02 2009-05-19 Bristol-Myers Squibb Company Sustained release GLP-1 receptor modulators
AR051446A1 (es) 2004-09-23 2007-01-17 Bristol Myers Squibb Co Glucosidos de c-arilo como inhibidores selectivos de transportadores de glucosa (sglt2)
US7517991B2 (en) 2004-10-12 2009-04-14 Bristol-Myers Squibb Company N-sulfonylpiperidine cannabinoid receptor 1 antagonists
US7635699B2 (en) 2004-12-29 2009-12-22 Bristol-Myers Squibb Company Azolopyrimidine-based inhibitors of dipeptidyl peptidase IV and methods
US7589088B2 (en) 2004-12-29 2009-09-15 Bristol-Myers Squibb Company Pyrimidine-based inhibitors of dipeptidyl peptidase IV and methods
US7314882B2 (en) 2005-01-12 2008-01-01 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid receptor modulators
US7220859B2 (en) 2005-01-12 2007-05-22 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid receptor modulators
WO2006076597A1 (en) 2005-01-12 2006-07-20 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid receptor modulators
US20060160850A1 (en) 2005-01-18 2006-07-20 Chongqing Sun Bicyclic heterocycles as cannabinoid receptor modulators
US20060235028A1 (en) 2005-04-14 2006-10-19 Li James J Inhibitors of 11-beta hydroxysteroid dehydrogenase type I
US7521557B2 (en) 2005-05-20 2009-04-21 Bristol-Myers Squibb Company Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods
US7632837B2 (en) 2005-06-17 2009-12-15 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid-1 receptor modulators
US7317012B2 (en) 2005-06-17 2008-01-08 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoind-1 receptor modulators
US7572808B2 (en) 2005-06-17 2009-08-11 Bristol-Myers Squibb Company Triazolopyridine cannabinoid receptor 1 antagonists
US7452892B2 (en) 2005-06-17 2008-11-18 Bristol-Myers Squibb Company Triazolopyrimidine cannabinoid receptor 1 antagonists
US7629342B2 (en) 2005-06-17 2009-12-08 Bristol-Myers Squibb Company Azabicyclic heterocycles as cannabinoid receptor modulators
AR056155A1 (es) 2005-10-26 2007-09-19 Bristol Myers Squibb Co Antagonistas del receptor 1 de la hormona de concentracion de melanina no basica
EP1943215A2 (en) 2005-10-31 2008-07-16 Brystol-Myers Squibb Company Pyrrolidinyl beta-amino amide-based inhibitors of dipeptidyl peptidase iv and methods
US7592461B2 (en) 2005-12-21 2009-09-22 Bristol-Myers Squibb Company Indane modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof
US7553836B2 (en) 2006-02-06 2009-06-30 Bristol-Myers Squibb Company Melanin concentrating hormone receptor-1 antagonists
WO2007139589A1 (en) 2006-05-26 2007-12-06 Bristol-Myers Squibb Company Sustained release glp-1 receptor modulators
US7919598B2 (en) 2006-06-28 2011-04-05 Bristol-Myers Squibb Company Crystal structures of SGLT2 inhibitors and processes for preparing same
WO2008057862A2 (en) 2006-11-01 2008-05-15 Bristol-Myers Squibb Company MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-ϰB ACTIVITY AND USE THEREOF
PE20090185A1 (es) 2007-03-22 2009-02-28 Bristol Myers Squibb Co Formulaciones farmaceuticas que contienen un inhibidor sglt2
PE20090696A1 (es) 2007-04-20 2009-06-20 Bristol Myers Squibb Co Formas cristalinas de saxagliptina y procesos para preparar las mismas
EP2581081A3 (en) 2007-06-01 2013-07-31 The Trustees Of Princeton University Treatment of viral infections by modulation of host cell metabolic pathways
US20090011994A1 (en) 2007-07-06 2009-01-08 Bristol-Myers Squibb Company Non-basic melanin concentrating hormone receptor-1 antagonists and methods
JP2010534722A (ja) 2007-07-27 2010-11-11 ブリストル−マイヤーズ スクイブ カンパニー 新規グルコキナーゼ活性化薬およびその使用方法
BRPI0817211A2 (pt) 2007-09-20 2017-05-16 Irm Llc composto composições como moduladores da atividade de gpr119
PE20091928A1 (es) 2008-05-29 2009-12-31 Bristol Myers Squibb Co Tienopirimidinas hidroxisustituidas como antagonistas de receptor-1 de hormona concentradora de melanina no basicos
WO2010111665A1 (en) 2009-03-27 2010-09-30 Bristol-Myers Squibb Company Methods for preventing major adverse cardiovascular events with dpp-iv inhibitors
WO2011014520A2 (en) 2009-07-29 2011-02-03 Irm Llc Compounds and compositions as modulators of gpr119 activity
KR20120092629A (ko) 2009-10-09 2012-08-21 아이알엠 엘엘씨 Ｇｐｒ119 활성의 조절제로서의 화합물 및 조성물
CA2780941C (en) 2009-11-13 2018-06-12 Bristol-Myers Squibb Company Immediate release tablet formulations
EP2498757A1 (en) 2009-11-13 2012-09-19 Bristol-Myers Squibb Company Reduced mass metformin formulations
HUE040486T2 (hu) 2009-11-13 2019-03-28 Astrazeneca Ab Kétrétegû tabletta készítmények
US8394858B2 (en) 2009-12-03 2013-03-12 Novartis Ag Cyclohexane derivatives and uses thereof
TWI562775B (en) 2010-03-02 2016-12-21 Lexicon Pharmaceuticals Inc Methods of using inhibitors of sodium-glucose cotransporters 1 and 2
US8592396B2 (en) 2010-04-14 2013-11-26 Bristol-Myers Squibb Company Glucokinase activators and methods of using same
AU2011276254B2 (en) 2010-07-09 2016-11-03 James Trinca Green Combination immediate/delayed release delivery system for short half-life pharmaceuticals including remogliflozin
US8697739B2 (en) 2010-07-29 2014-04-15 Novartis Ag Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof
TWI631963B (zh) 2011-01-05 2018-08-11 雷西肯製藥股份有限公司 包含鈉－葡萄糖共同輸送體１與２之抑制劑的組合物與應用方法
WO2014052619A1 (en) 2012-09-27 2014-04-03 Irm Llc Piperidine derivatives and compositions as modulators of gpr119 activity
NZ707859A (en) 2012-11-20 2019-03-29 Lexicon Pharmaceuticals Inc Inhibitors of sodium glucose cotransporter 1
US9593113B2 (en) 2013-08-22 2017-03-14 Bristol-Myers Squibb Company Imide and acylurea derivatives as modulators of the glucocorticoid receptor
CN104610262B (zh) * 2013-11-01 2017-06-06 上海医药工业研究院 联苯类化合物、中间体、制备方法、药物组合物及其应用
JP2018515082A (ja) 2015-04-30 2018-06-14 プレジデント アンド フェローズ オブ ハーバード カレッジ 代謝障害を処置するための抗ａｐ２抗体及び抗原結合剤
BR112021000139A2 (pt) 2018-07-19 2021-04-06 Astrazeneca Ab Métodos de tratamento da hfpef empregando dapagliflozina e composições compreendendo a mesma
BR112021004839A2 (pt) 2018-09-26 2021-06-08 Lexicon Pharmaceuticals, Inc. formas cristalinas de n-(1-((2-(dimetilamino)etil)amino)-2-metil-1-oxopropan-2-il)-4-(4-(2-metil-5-((2s,3r,4r,5s,6r)-3,4,5-triidróxi-6-(metiltio)tetraidro-2h-piran-2-il)benzil)fenil)butanamida e métodos de sua síntese

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA828650B (en) * 1981-12-01 1983-09-28 Hunt Chem Corp Philip A Herbicidal compositions and method using phosphonalkanoic acids, esters and salts thereof
FR2596393B1 (fr) * 1986-04-01 1988-06-03 Sanofi Sa Derives de l'acide hydroxy-3 dihydroxyoxophosphorio-4 butanoique, leur procede de preparation, leur application comme medicament et les compositions les renfermant
SE501541C2 (sv) * 1987-05-22 1995-03-06 Squibb & Sons Inc Fosforhaltiga HMG-CoA reduktasinhibitorer, nya mellanprodukter och metod

Also Published As

Publication number Publication date
IL86464A (en) 1993-06-10
GR1000959B (el) 1993-03-16
BE1004193A3 (fr) 1992-10-13
PT87539A (pt) 1989-05-31
DE3817375A1 (de) 1988-12-08
FI882384A (fi) 1988-11-23
NZ224733A (en) 1990-12-21
SE8801903D0 (sv) 1988-05-20
GB8811929D0 (en) 1988-06-22
IT1217685B (it) 1990-03-30
JPS6456689A (en) 1989-03-03
IE881543L (en) 1988-11-22
GR880100331A (en) 1989-02-23
GB2205837A (en) 1988-12-21
NL8801330A (nl) 1988-12-16
KR880013958A (ko) 1988-12-22
HU205125B (en) 1992-03-30
AU610591B2 (en) 1991-05-23
SE8801903L (sv) 1988-11-23
CN88103091A (zh) 1988-12-21
DK277488A (da) 1988-11-23
NO882218D0 (no) 1988-05-20
PL272597A1 (en) 1989-03-06
FI89493B (fi) 1993-06-30
IL86464A0 (en) 1988-11-15
IT8820682A0 (it) 1988-05-20
AU1650888A (en) 1988-11-24
NO882218L (no) 1988-11-23
IE63760B1 (en) 1995-06-14
SE503210C2 (sv) 1996-04-22
FR2615508A1 (fr) 1988-11-25
HUT49358A (en) 1989-09-28
IE930324L (en) 1988-11-22
PH25350A (en) 1991-05-13
FI882384A0 (fi) 1988-05-20
DE3817375C2 (de) 1997-04-30
PL154877B1 (en) 1991-09-30
JP2680347B2 (ja) 1997-11-19
PT87539B (pt) 1992-09-30
FR2615508B1 (fr) 1994-11-25
DK277488D0 (da) 1988-05-20
CH676984A5 (sv) 1991-03-28
ES2009918A6 (es) 1989-10-16
GB2205837B (en) 1991-11-20

Similar Documents

Publication Publication Date Title
FI89493C (sv) Förfarande för framställning av terapeutiskt aktiva, fosforhaltiga inh ibitorer av HMG-CoA-reduktas och vid förfarandet användbar ny mellanpr odukt
US4904646A (en) Phosphorus-containing HMG-COA reductase inhibitors
US5017716A (en) Phosphorous-containing HMG-CoA reductase inhibitors, new intermediates and method
AU612475B2 (en) Phenol substituted gem-diphosphonate derivatives, process for their preparation and pharmaceutical compositions containing them
AU705206B2 (en) Compounds and pharmaceutical compositions containing them
JPH0665267A (ja) リン含有ＨＭＧ−ＣｏＡリダクターゼ抑制剤および新規中間体
EP0946572B1 (en) Pharmaceutical aminophosphonic acid derivatives
DE3805801C2 (de) Antihypercholesterinämisch wirkende Tetrazol-Verbindungen, Verfahren zu ihrer Herstellung und pharmazeutische Mittel
FI87927B (fi) Foerfarande foer framstaellining av nya fosforhaltiga hmg-coa-reduktasinhibitorer och nya mellanprodukter
US5618964A (en) Prodrug esters of phosphonosulfonate squalene synthetase inhibitors and method
US5278153A (en) Aryl and heteroaryl (phosphinylmethyl)phosphonate squalene synthetase inhibitors and method
WO1998028312A1 (en) Pharmaceutical aminophosphonic acid derivatives
US4702864A (en) Analogs of platelet activating factor
Iyer et al. Synthesis, hydrolytic behavior, and anti-HIV activity of selected acyloxyalkyl esters of trisodium phosphonoformate (foscarnet sodium)
US5428028A (en) Method for lowering cholesterol employing a phosphonomethylphosphinate squalene synthetase inhibitor
PH26228A (en) An intermediate for the preparation of phosphorous containing CoA reductase inhibitors
GB2235924A (en) Phosphorus-containing 3-hydroxy-butanoic acid intermediates
JPS63208596A (ja) 新規な抗菌剤およびカルバペネム抗生物質の効力増強剤
DD270714A5 (de) Verfahren zur herstellung von phosphorhaltigen hmg-coa reduktase-inhibitoren

Legal Events

Date Code Title Description
BB Publication of examined application
FG Patent granted

Owner name: E.R. SQUIBB & SONS, INC.

MA Patent expired