AU577815B2 - Phenyl acetic acid amides - Google Patents

Phenyl acetic acid amides

Info

Publication number
AU577815B2
AU577815B2 AU37210/84A AU3721084A AU577815B2 AU 577815 B2 AU577815 B2 AU 577815B2 AU 37210/84 A AU37210/84 A AU 37210/84A AU 3721084 A AU3721084 A AU 3721084A AU 577815 B2 AU577815 B2 AU 577815B2
Authority
AU
Australia
Prior art keywords
acetic acid
acid amides
phenyl acetic
kbr
degrees
Prior art date
Legal status (The legal status 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 status listed.)
Expired
Application number
AU37210/84A
Other versions
AU3721084A (en
Inventor
Wolfgang Grell
Gerhart Griss
Rudolf Hurnaus
Eckhard Rupprecht
Robert Sauter
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim Pharma GmbH and Co KG
Original Assignee
Dr Karl Thomae 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.)
Filing date
Publication date
Application filed by Dr Karl Thomae GmbH filed Critical Dr Karl Thomae GmbH
Publication of AU3721084A publication Critical patent/AU3721084A/en
Application granted granted Critical
Publication of AU577815B2 publication Critical patent/AU577815B2/en
Anticipated expiration legal-status Critical
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Hydrogenated Pyridines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Superconductors And Manufacturing Methods Therefor (AREA)
  • Lubricants (AREA)
  • Glass Compositions (AREA)

Abstract

1. Two new solid forms of 2-ethoxy-4-[N-(1-(2-piperidino- phenyl)-3-methyl-1-butyl)-aminocarbonylmethyl]-benzoic acid, the form designated (B) being characterised by the melting point of 140-142 degrees C and by the IR(KBr) spectrum according to Figure B' and the form designated (C) being characterised by a melting point of 75-85 degrees C and by the IR(KBr) spectrum according to Figure C'.
AU37210/84A 1983-12-30 1984-12-28 Phenyl acetic acid amides Expired AU577815B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19833347565 DE3347565A1 (en) 1983-12-30 1983-12-30 NEW PHENYL ACETIC DERIVATIVES, MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF
DE3347565 1983-12-30
DE19853522604 DE3522604A1 (en) 1983-12-30 1985-06-25 NEW SOLID FORMS OF 2- (GAMMA) THOXY-4- (N- (1- (2- (2-PIPERIDINO-PHENYL) -3-METHYL-1-BUTYL) -AMINOCARBONYLMETHYL) -BENZOESIC ACID, MEDICINAL PRODUCTS CONTAINING THESE FORMS

Publications (2)

Publication Number Publication Date
AU3721084A AU3721084A (en) 1985-08-01
AU577815B2 true AU577815B2 (en) 1988-10-06

Family

ID=37847099

Family Applications (2)

Application Number Title Priority Date Filing Date
AU37210/84A Expired AU577815B2 (en) 1983-12-30 1984-12-28 Phenyl acetic acid amides
AU59139/86A Expired AU583631B2 (en) 1983-12-30 1986-06-24 Solid forms of 2-ethoxy-4-``N-(1-(2-piperidino-phenyl)-3- methyl-1-butyl)-aminocarbonylmethyl``-benzoic acid

Family Applications After (1)

Application Number Title Priority Date Filing Date
AU59139/86A Expired AU583631B2 (en) 1983-12-30 1986-06-24 Solid forms of 2-ethoxy-4-``N-(1-(2-piperidino-phenyl)-3- methyl-1-butyl)-aminocarbonylmethyl``-benzoic acid

Country Status (26)

Country Link
EP (2) EP0147850B1 (en)
JP (2) JPH0623200B2 (en)
KR (1) KR900005320B1 (en)
AT (1) ATE44027T1 (en)
AU (2) AU577815B2 (en)
BG (1) BG61519B2 (en)
CA (2) CA1225398A (en)
CS (1) CS409791A3 (en)
DD (1) DD231348A5 (en)
DE (4) DE3347565A1 (en)
DK (2) DK167439B1 (en)
ES (7) ES8605500A1 (en)
FI (2) FI80447C (en)
GR (2) GR82614B (en)
HK (1) HK87492A (en)
HU (1) HU194548B (en)
IE (1) IE57700B1 (en)
IL (2) IL73963A (en)
LU (1) LU90301I2 (en)
MX (1) MX9202772A (en)
NL (1) NL980034I1 (en)
NO (3) NO162819C (en)
NZ (2) NZ210657A (en)
PT (2) PT79772B (en)
SG (1) SG55492G (en)
ZA (2) ZA8410103B (en)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3523466A1 (en) * 1985-07-01 1987-01-08 Thomae Gmbh Dr K NEW PHENYL ACETIC DERIVATIVES, MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF
DE3347565A1 (en) * 1983-12-30 1985-07-11 Thomae Gmbh Dr K NEW PHENYL ACETIC DERIVATIVES, MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF
AU660930B2 (en) * 1991-06-21 1995-07-13 Novo Nordisk A/S (S)(+)-2-ethoxy-4-(N-(1-(2-piperidinophenyl)-3-methyl-1- butyl)aminocarbonylmethyl)benzoic acid
ATE223391T1 (en) * 1991-06-21 2002-09-15 Boehringer Ingelheim Pharma METHOD FOR PRODUCING (S)-3-METHYL-1-(2-PIPERIDINO-PHENYL)-1-BUTYLAMIN
FR2763590B1 (en) * 1997-05-22 2000-03-24 Synthelabo ACID DERIVATIVES [[[(ARYLMETHYL) AMINO] CARBONYL] ALKYL] - AROMATICS, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
EP1741447B1 (en) 2000-01-21 2013-09-18 Novartis AG Combinations comprising dipeptidylpeptidase-IV inhibitors and antidiabetic agents
US20040102477A1 (en) * 2002-08-23 2004-05-27 Dr. Reddy's Laboratories Limited Polymorphic forms of (S)-Repaglinide and the processes for preparation thereof
EP1636199A2 (en) * 2003-05-14 2006-03-22 Cilag AG Method for the production of phenylacetic acid derivatives
AU2003237595A1 (en) * 2003-05-26 2004-12-13 Biocon Limited Process for the preparation of s(+)-2-ethoxy-4-(n-{1-(2-piperidinophelyl)-3-methyl-1- butyl} aminocarbonylmethyl)benzoic acid derivatives
CA2526506A1 (en) * 2003-06-09 2004-12-16 Boehringer Ingelheim International Gmbh Inhibitors of papilloma virus
FR2875805B1 (en) * 2004-09-27 2006-12-29 Genfit S A SUBSTITUTED N- (BENZYL) PHENYLACETAMIDE DERIVATIVE COMPOUNDS, PREPARATION AND USES
CN1305863C (en) * 2004-12-27 2007-03-21 浙江大学 Method for synthesizing (S)-isopropyl-(2-piperidine) phenyl-methylhistamine
GT200600381A (en) 2005-08-25 2007-03-28 ORGANIC COMPOUNDS
WO2007033266A2 (en) 2005-09-14 2007-03-22 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors for treating diabetis
EP2177221A1 (en) 2008-10-20 2010-04-21 Krka Tovarna Zdravil, D.D., Novo Mesto Process for the preparation of substantially optically pure Repaglinide and precursors thereof
MX2011012199A (en) 2009-05-15 2011-12-08 Novartis Ag Benzoxazolone derivatives as aldosterone symthase inhibitors.
WO2010130796A1 (en) 2009-05-15 2010-11-18 Novartis Ag Aryl pyridine as aldosterone synthase inhibitors
BRPI1011657A2 (en) 2009-05-28 2019-04-16 Novartis Ag substituted aminopropionic derivatives as neprilysin inhibitors
EA201101672A1 (en) 2009-05-28 2012-06-29 Новартис Аг SUBSTITUTED DERIVATIVES OF AMINOISAL ACID AS NEPRILISIN INHIBITORS
WO2011041293A1 (en) 2009-09-30 2011-04-07 Takeda Pharmaceutical Company Limited Pyrazolo [1, 5-a] pyrimidine derivatives as apoptosis signal-regulating kinase 1 inhibitors
JP5654608B2 (en) 2009-11-17 2015-01-14 ノバルティス アーゲー Aryl-pyridine derivatives as aldosterone synthase inhibitors
JO2967B1 (en) 2009-11-20 2016-03-15 نوفارتس ايه جي Substituted carbamoylmethylamino acetic acid derivatives as novel NEP inhibitors
ES2472446T3 (en) 2009-11-30 2014-07-01 Novartis Ag Imidazole derivatives as aldosterone synthase inhibitors
SI2531501T1 (en) 2010-02-03 2014-04-30 Takeda Pharmaceutical Company Limited Apoptosis signal-regulating kinase 1 inhibitors
US8673974B2 (en) 2010-11-16 2014-03-18 Novartis Ag Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors
US8877815B2 (en) 2010-11-16 2014-11-04 Novartis Ag Substituted carbamoylcycloalkyl acetic acid derivatives as NEP
WO2012095548A2 (en) 2011-01-13 2012-07-19 Centro De Investigación Biomédica En Red De Enfermedades Neurodegenerativas (Ciberned) Compounds for treating neurodegenerative disorders
UY35144A (en) 2012-11-20 2014-06-30 Novartis Ag APELINE SYNTHETIC LINEAR MIMETICS FOR THE CARDIAC INSUFFICIENCY TREATMENT
LT2956464T (en) 2013-02-14 2018-07-10 Novartis Ag Substituted bisphenyl butanoic phosphonic acid derivatives as nep (neutral endopeptidase) inhibitors
MX2016001020A (en) 2013-07-25 2016-08-03 Novartis Ag Cyclic polypeptides for the treatment of heart failure.
US9340582B2 (en) 2013-07-25 2016-05-17 Novartis Ag Bioconjugates of synthetic apelin polypeptides
AU2016209968B2 (en) 2015-01-23 2018-11-29 Novartis Ag Synthetic apelin fatty acid conjugates with improved half-life
UY38072A (en) 2018-02-07 2019-10-01 Novartis Ag COMPOSITIONS DERIVED FROM BUTANOIC ESTER SUBSTITUTED WITH BISPHENYL AS INHIBITORS OF NEP, COMPOSITIONS AND COMBINATIONS OF THE SAME

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU7929082A (en) * 1981-01-10 1982-07-22 Dr. Karl Thomae Gmbh N-substituted polymethyleneimines
AU557959B2 (en) * 1981-01-10 1987-01-15 Dr. Karl Thomae Gmbh Aryl amides
AU561274B2 (en) * 1982-07-06 1987-05-07 Dr. Karl Thomae Gmbh Phenyl acetic acid amides

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2554875B1 (en) * 1983-11-10 1986-02-28 Dba HYDRAULIC BRAKE AMPLIFIER
DE3523466A1 (en) * 1985-07-01 1987-01-08 Thomae Gmbh Dr K NEW PHENYL ACETIC DERIVATIVES, MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF
DE3347565A1 (en) * 1983-12-30 1985-07-11 Thomae Gmbh Dr K NEW PHENYL ACETIC DERIVATIVES, MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU7929082A (en) * 1981-01-10 1982-07-22 Dr. Karl Thomae Gmbh N-substituted polymethyleneimines
AU557959B2 (en) * 1981-01-10 1987-01-15 Dr. Karl Thomae Gmbh Aryl amides
AU561274B2 (en) * 1982-07-06 1987-05-07 Dr. Karl Thomae Gmbh Phenyl acetic acid amides

Also Published As

Publication number Publication date
ES545883A0 (en) 1986-02-01
ZA864695B (en) 1988-02-24
IL73963A0 (en) 1985-03-31
HU194548B (en) 1988-02-29
DK296686A (en) 1986-12-26
JPS60158171A (en) 1985-08-19
CA1225398A (en) 1987-08-11
NO162819B (en) 1989-11-13
NO862532D0 (en) 1986-06-24
ES545881A0 (en) 1986-02-01
IL73963A (en) 1989-01-31
GR861558B (en) 1986-10-17
KR850004590A (en) 1985-07-25
NO162819C (en) 1990-02-21
DK167573B1 (en) 1993-11-22
GR82614B (en) 1985-05-02
HUT37773A (en) 1986-02-28
ES545879A0 (en) 1986-02-01
IL79217A0 (en) 1986-09-30
CS409791A3 (en) 1992-07-15
PT82832A (en) 1986-07-01
IE57700B1 (en) 1993-03-10
EP0207331A1 (en) 1987-01-07
LU90301I2 (en) 1998-12-21
DE3522604A1 (en) 1987-01-08
ES539078A0 (en) 1986-03-16
IL79217A (en) 1991-01-31
PT79772A (en) 1985-01-01
FI80447C (en) 1990-06-11
JPS62474A (en) 1987-01-06
AU3721084A (en) 1985-08-01
BG61519B2 (en) 1997-10-31
ZA8410103B (en) 1986-09-24
JPH0739405B2 (en) 1995-05-01
FI845145A0 (en) 1984-12-28
FI82689B (en) 1990-12-31
NO862532L (en) 1986-12-29
FI82689C (en) 1991-04-10
DD231348A5 (en) 1985-12-24
ES8802145A1 (en) 1988-04-01
AU583631B2 (en) 1989-05-04
PT79772B (en) 1987-01-05
FI862650A (en) 1986-12-26
DE3478682D1 (en) 1989-07-20
ES556495A0 (en) 1988-04-01
DE19875044I2 (en) 2002-07-18
ES545882A0 (en) 1986-02-01
CA1292000C (en) 1991-11-12
AU5913986A (en) 1987-01-08
NZ210657A (en) 1988-10-28
EP0207331B1 (en) 1990-05-23
NL980034I1 (en) 1999-02-01
PT82832B (en) 1988-12-15
FI845145L (en) 1985-07-01
KR900005320B1 (en) 1990-07-27
ES8604548A1 (en) 1986-02-01
ES545880A0 (en) 1986-02-01
ES8604546A1 (en) 1986-02-01
MX9202772A (en) 1992-06-30
ATE44027T1 (en) 1989-06-15
NO168302B (en) 1991-10-28
NO845282L (en) 1985-07-01
EP0147850B1 (en) 1989-06-14
DK613184D0 (en) 1984-12-20
IE843349L (en) 1985-06-30
FI80447B (en) 1990-02-28
ES8604544A1 (en) 1986-02-01
EP0147850A2 (en) 1985-07-10
NO168302C (en) 1992-02-05
DK613184A (en) 1985-07-01
JPH0623200B2 (en) 1994-03-30
DK296686D0 (en) 1986-06-24
ES8605500A1 (en) 1986-03-16
EP0147850A3 (en) 1985-08-07
NZ216640A (en) 1989-02-24
SG55492G (en) 1992-10-02
ES8604545A1 (en) 1986-02-01
FI862650A0 (en) 1986-06-23
HK87492A (en) 1992-11-13
DE3347565A1 (en) 1985-07-11
ES8604547A1 (en) 1986-02-01
DK167439B1 (en) 1993-11-01
NO1999016I1 (en) 1999-07-20

Similar Documents

Publication Publication Date Title
AU577815B2 (en) Phenyl acetic acid amides

Legal Events

Date Code Title Description
NC Extension of term for standard patent requested (sect. 70)

Free format text: PRODUCT NAME: NOVONORM (REPAGLINIDE)

NCW Application for extension of term withdrawn (under section 73 patents act 1990)

Free format text: PRODUCT NAME: NOVONORM (REPAGLINIDE)