FI942910A - Uusia fosfonimeripihkahappojohdannaisia, menetelmä niiden valmistamiseksi ja näitä yhdisteitä sisältäviä lääkkeitä - Google Patents

Uusia fosfonimeripihkahappojohdannaisia, menetelmä niiden valmistamiseksi ja näitä yhdisteitä sisältäviä lääkkeitä Download PDF

Info

Publication number: FI942910A
Authority: FI; Finland
Prior art keywords: pct; compounds; lower alkyl; date jun; preparation
Prior art date: 1991-12-19

Application number

FI942910A

Other languages

English (en)

Swedish (sv)

Other versions

FI942910A0 (fi

Inventor

Christos Tsaklakidis

Elmar Bosies

Angelika Esswein

Frieder Bauss

Original Assignee

Boehringer Mannheim Gmbh

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.)

1991-12-19

Filing date

1994-06-17

Publication date

1994-06-17

1994-06-17 Application filed by Boehringer Mannheim Gmbh filed Critical Boehringer Mannheim Gmbh

1994-06-17 Publication of FI942910A0 publication Critical patent/FI942910A0/fi

1994-06-17 Publication of FI942910A publication Critical patent/FI942910A/fi

Links

150000001875 compounds Chemical class 0.000 title abstract 3
239000003814 drug Substances 0.000 title abstract 2
238000000034 method Methods 0.000 title abstract 2
KMDMOMDSEVTJTI-UHFFFAOYSA-N 2-phosphonobutanedioic acid Chemical class OC(=O)CC(C(O)=O)P(O)(O)=O KMDMOMDSEVTJTI-UHFFFAOYSA-N 0.000 title 1
229940079593 drug Drugs 0.000 title 1
125000000217 alkyl group Chemical group 0.000 abstract 3
229910052739 hydrogen Inorganic materials 0.000 abstract 2
239000001257 hydrogen Substances 0.000 abstract 2
125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 2
229920006395 saturated elastomer Polymers 0.000 abstract 2
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 abstract 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract 1
125000003342 alkenyl group Chemical group 0.000 abstract 1
125000006193 alkinyl group Chemical group 0.000 abstract 1
125000002947 alkylene group Chemical group 0.000 abstract 1
125000003277 amino group Chemical group 0.000 abstract 1
125000006615 aromatic heterocyclic group Chemical group 0.000 abstract 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 1
229910052791 calcium Inorganic materials 0.000 abstract 1
239000011575 calcium Substances 0.000 abstract 1
125000004432 carbon atom Chemical group C* 0.000 abstract 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 abstract 1
229910052736 halogen Inorganic materials 0.000 abstract 1
150000002367 halogens Chemical class 0.000 abstract 1
230000002503 metabolic effect Effects 0.000 abstract 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract 1
150000003839 salts Chemical class 0.000 abstract 1

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 Table
- 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 ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or 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
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
- 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 Table
- 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 ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or 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 Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/5532—Seven-(or more) membered rings
- 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 Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- 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 Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
- 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 Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Endocrinology (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

FI942910A 1991-12-19 1994-06-17 Uusia fosfonimeripihkahappojohdannaisia, menetelmä niiden valmistamiseksi ja näitä yhdisteitä sisältäviä lääkkeitä FI942910A (fi)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE4141928A DE4141928A1 (de)	1991-12-19	1991-12-19	Neue phosphonobernsteinsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel
PCT/EP1992/002890 WO1993012122A1 (de)	1991-12-19	1992-12-14	Neue phosphonobernsteinsäurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel

Publications (2)

Publication Number	Publication Date
FI942910A0 FI942910A0 (fi)	1994-06-17
FI942910A true FI942910A (fi)	1994-06-17

Family

ID=6447460

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI942910A FI942910A (fi)	1991-12-19	1994-06-17	Uusia fosfonimeripihkahappojohdannaisia, menetelmä niiden valmistamiseksi ja näitä yhdisteitä sisältäviä lääkkeitä

Country Status (22)

Country	Link
US (2)	US5538957A (fi)
EP (1)	EP0618920B1 (fi)
JP (1)	JPH07507046A (fi)
AT (1)	ATE141277T1 (fi)
AU (1)	AU662790B2 (fi)
CA (1)	CA2125867A1 (fi)
CZ (1)	CZ151894A3 (fi)
DE (2)	DE4141928A1 (fi)
DK (1)	DK0618920T3 (fi)
ES (1)	ES2093399T3 (fi)
FI (1)	FI942910A (fi)
GR (1)	GR3021110T3 (fi)
HU (1)	HUT66771A (fi)
IL (1)	IL104090A (fi)
MX (1)	MX9207335A (fi)
NO (1)	NO300546B1 (fi)
NZ (1)	NZ246152A (fi)
RU (1)	RU2115656C1 (fi)
SK (1)	SK74694A3 (fi)
TW (1)	TW222636B (fi)
WO (1)	WO1993012122A1 (fi)
ZA (1)	ZA929815B (fi)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5760021A (en) *	1992-05-29	1998-06-02	The Procter & Gamble Company	Phosphonocarboxylate compounds pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism
DE4320223A1 (de) *	1993-06-18	1994-12-22	Boehringer Mannheim Gmbh	Neue Phosphonobernsteinsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
DE4336099A1 (de) *	1993-10-22	1995-04-27	Boehringer Mannheim Gmbh	Neue 2.4-Diphosphonoglutarsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
DE4410601A1 (de) *	1994-03-26	1995-09-28	Boehringer Mannheim Gmbh	Neue 2.4-Diphosphonoglutarsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
US6011021A (en) *	1996-06-17	2000-01-04	Guilford Pharmaceuticals Inc.	Methods of cancer treatment using naaladase inhibitors
GB2313126A (en) *	1996-05-14	1997-11-19	Albright & Wilson Uk Ltd	Polymer compositions containing phosphorus
US5795877A (en) *	1996-12-31	1998-08-18	Guilford Pharmaceuticals Inc.	Inhibitors of NAALADase enzyme activity
US5672592A (en) *	1996-06-17	1997-09-30	Guilford Pharmaceuticals Inc.	Certain phosphonomethyl-pentanedioic acid derivatives thereof
US6071965A (en) *	1996-06-17	2000-06-06	Guilford Pharmaceuticals Inc.	Phosphinic alkanoic acid derivatives
US6025344A (en) *	1996-06-17	2000-02-15	Guilford Pharmaceuticals Inc.	Certain dioic acid derivatives useful as NAALADase inhibitors
US6384022B1 (en)	1996-06-17	2002-05-07	Guilford Pharmaceuticals Inc.	Prodrugs of NAALAdase inhibitors
US5902817A (en) *	1997-04-09	1999-05-11	Guilford Pharmaceuticals Inc.	Certain sulfoxide and sulfone derivatives
US6025345A (en) *	1996-06-17	2000-02-15	Guilford Pharmaceuticals Inc.	Inhibitors of NAALADase enzyme activity
US6046180A (en) *	1996-06-17	2000-04-04	Guilford Pharmaceuticals Inc.	NAALADase inhibitors
IL127605A0 (en)	1996-06-17	1999-10-28	Guilford Pharm Inc	Methods of cancer treatment using naaladase inhibitors
US6054444A (en)	1997-04-24	2000-04-25	Guilford Pharmaceuticals Inc.	Phosphonic acid derivatives
US5977090A (en) *	1996-09-27	1999-11-02	Guilford Pharmaceuticals Inc.	Pharmaceutical compositions and methods of treating compulsive disorders using NAALADase inhibitors
US5863536A (en) *	1996-12-31	1999-01-26	Guilford Pharmaceuticals Inc.	Phosphoramidate derivatives
US5962521A (en)	1997-04-04	1999-10-05	Guilford Pharmaceuticals Inc.	Hydroxamic acid derivatives
US5981209A (en) *	1997-12-04	1999-11-09	Guilford Pharmaceuticals Inc.	Use of NAALADase activity to identify prostate cancer and benign prostatic hyperplasia
US6028216A (en) *	1997-12-31	2000-02-22	Guilford Pharmaceuticals Inc.	Asymmetric syntheses and intermediates for preparing enantiomer-enriched hydroxyphosphinyl derivatives
US6121252A (en) *	1998-03-30	2000-09-19	Guilford Pharmaceuticals Inc.	Phosphinic acid derivatives
CN1314882A (zh)	1998-07-06	2001-09-26	吉尔福德药物有限公司	用作药物化合物的naalad酶抑制剂和组合物
US6395718B1 (en) *	1998-07-06	2002-05-28	Guilford Pharmaceuticals Inc.	Pharmaceutical compositions and methods of inhibiting angiogenesis using naaladase inhibitors
US6265609B1 (en)	1998-07-06	2001-07-24	Guilford Pharmaceuticals Inc.	Thio-substituted pentanedioic acid derivatives
IT1303672B1 (it)	1998-07-28	2001-02-23	Nicox Sa	Sali nitrati di farmaci attivi nei disordini ossei
US6313159B1 (en)	1999-08-20	2001-11-06	Guilford Pharmaceuticals Inc.	Metabotropic glutamate receptor ligand derivatives as naaladase inhibitors
WO2002034204A2 (en) *	2000-10-25	2002-05-02	Smithkline Beecham Corporation	Calcilytic compounds

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2360797C2 (de) *	1973-12-06	1985-05-23	Henkel KGaA, 4000 Düsseldorf	Pharmazeutische Präparate
IL77243A (en) *	1984-12-21	1996-11-14	Procter & Gamble	Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds
US5004549A (en) *	1989-10-10	1991-04-02	Olin Corporation	Method for inhibiting scale formation using calcium hypochlorite compositions

1991
- 1991-12-19 DE DE4141928A patent/DE4141928A1/de not_active Withdrawn
1992
- 1992-12-01 TW TW081109635A patent/TW222636B/zh active
- 1992-12-14 NZ NZ246152A patent/NZ246152A/en unknown
- 1992-12-14 DE DE59206925T patent/DE59206925D1/de not_active Expired - Fee Related
- 1992-12-14 EP EP93900042A patent/EP0618920B1/de not_active Expired - Lifetime
- 1992-12-14 HU HU9401834A patent/HUT66771A/hu unknown
- 1992-12-14 AU AU31580/93A patent/AU662790B2/en not_active Ceased
- 1992-12-14 US US08/244,245 patent/US5538957A/en not_active Expired - Fee Related
- 1992-12-14 ES ES93900042T patent/ES2093399T3/es not_active Expired - Lifetime
- 1992-12-14 IL IL104090A patent/IL104090A/xx not_active IP Right Cessation
- 1992-12-14 DK DK93900042.8T patent/DK0618920T3/da active
- 1992-12-14 SK SK746-94A patent/SK74694A3/sk unknown
- 1992-12-14 CZ CZ941518A patent/CZ151894A3/cs unknown
- 1992-12-14 JP JP5510624A patent/JPH07507046A/ja active Pending
- 1992-12-14 CA CA002125867A patent/CA2125867A1/en not_active Abandoned
- 1992-12-14 RU RU94030812A patent/RU2115656C1/ru active
- 1992-12-14 WO PCT/EP1992/002890 patent/WO1993012122A1/de not_active Application Discontinuation
- 1992-12-14 AT AT93900042T patent/ATE141277T1/de active
- 1992-12-16 MX MX9207335A patent/MX9207335A/es not_active IP Right Cessation
- 1992-12-18 ZA ZA929815A patent/ZA929815B/xx unknown
1994
- 1994-06-17 NO NO942304A patent/NO300546B1/no not_active IP Right Cessation
- 1994-06-17 FI FI942910A patent/FI942910A/fi unknown
1995
- 1995-06-05 US US08/465,360 patent/US5627170A/en not_active Expired - Fee Related
1996
- 1996-09-19 GR GR960402474T patent/GR3021110T3/el unknown

Also Published As

Publication number	Publication date
SK74694A3 (en)	1995-02-08
TW222636B (fi)	1994-04-21
GR3021110T3 (en)	1996-12-31
DK0618920T3 (da)	1996-12-30
HU9401834D0 (en)	1994-09-28
US5538957A (en)	1996-07-23
MX9207335A (es)	1993-06-01
WO1993012122A1 (de)	1993-06-24
CA2125867A1 (en)	1993-06-24
ES2093399T3 (es)	1996-12-16
DE4141928A1 (de)	1993-06-24
IL104090A (en)	1997-03-18
EP0618920A1 (de)	1994-10-12
AU3158093A (en)	1993-07-19
CZ151894A3 (en)	1995-01-18
EP0618920B1 (de)	1996-08-14
DE59206925D1 (de)	1996-09-19
JPH07507046A (ja)	1995-08-03
NO942304L (fi)	1994-08-16
AU662790B2 (en)	1995-09-14
FI942910A0 (fi)	1994-06-17
IL104090A0 (en)	1993-05-13
HUT66771A (en)	1994-12-28
ATE141277T1 (de)	1996-08-15
ZA929815B (en)	1994-06-20
NZ246152A (en)	1995-12-21
NO300546B1 (no)	1997-06-16
US5627170A (en)	1997-05-06
NO942304D0 (no)	1994-06-17
RU2115656C1 (ru)	1998-07-20

Legal Events

Date	Code	Title	Description
1999-05-30	HC	Name/ company changed in application	Owner name: ROCHE DIAGNOSTICS GMBH

Publication	Publication Date	Title
FI942910A (fi)	1994-06-17	Uusia fosfonimeripihkahappojohdannaisia, menetelmä niiden valmistamiseksi ja näitä yhdisteitä sisältäviä lääkkeitä
ZA911403B (en)	1991-11-27	Derivatives having a naphthalene structure,process for preparing these and pharmaceutical compositions containing them
DE69228879T2 (de)	1999-08-26	Amidino-derivate und ihre verwendung als no-synthase inhibitoren
ATE28565T1 (de)	1987-08-15	Spiro(4.(3+n))-2-aza-alkan-3-carbonsaeurederivate, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung.
MY102866A (en)	1993-03-31	Amide derivatives.
ES2070175T3 (es)	1995-06-01	Derivados de acido 4-oxoquinolino-3-carboxilico, su preparacion y su uso.
BR1101136A (pt)	1999-12-07	Derivado da pristinamicina iib, (dietilamino-2 metil-1 etil) sulfinil-26 pristinamicina iib, (dietilamino-2 propil) sulfonil-26 pristinamicina iib, (diisopropilamino-2 etil) sulfonil-26 pristinamicina iib, processo de preparação de novo derivado da pristinamicina iib e composição farmacêutica
ATE33831T1 (de)	1988-05-15	Analgesia wirkende 5-hydroxytryptophan-derivate.
SE8406302D0 (sv)	1984-12-12	New aminoguanidine derivatives and a process for the preparation thereof
ES2012648A6 (es)	1990-04-01	Procedimiento para la preparacion de nuevos derivados de 1,4-benzoxazina y 1,4-benzotiazina.
FI833453A (fi)	1984-03-31	Terapeutiska medel
ATE37368T1 (de)	1988-10-15	Benzothiazolon-derivate, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische zusammensetzungen.
ATE30152T1 (de)	1987-10-15	1-methyl-5-nitro-imidazolin-derivate und diese enthaltende therapeutische zusammensetzungen.
ATE29251T1 (de)	1987-09-15	Aminopyridincarbonsaeure-derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zusammensetzungen.
ES8604122A1 (es)	1986-01-16	Procedimiento de preparacion de eteres oximas basicos y de sus sales de adicion acidas farmaceuticamente aceptables
ATE25968T1 (de)	1987-04-15	1,1-diphenylpropanol-derivate, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen.