RU2011113690A - Новые ингибиторы дипептидилпептидазы iv (dp-iv) - Google Patents

Новые ингибиторы дипептидилпептидазы iv (dp-iv) Download PDF

Info

Publication number
RU2011113690A
RU2011113690A RU2011113690/04A RU2011113690A RU2011113690A RU 2011113690 A RU2011113690 A RU 2011113690A RU 2011113690/04 A RU2011113690/04 A RU 2011113690/04A RU 2011113690 A RU2011113690 A RU 2011113690A RU 2011113690 A RU2011113690 A RU 2011113690A
Authority
RU
Russia
Prior art keywords
meo
peptide
dpp
chloro
compound
Prior art date
Application number
RU2011113690/04A
Other languages
English (en)
Inventor
Бакулеш Мафатлал ХАМАР (IN)
Бакулеш Мафатлал Хамар
Сингх ЧАНДАН (IN)
Сингх ЧАНДАН
Раджив Индравадан МОДИ (IN)
Раджив Индравадан Моди
Original Assignee
Кадила Фармасьютикалз Лтд. (In)
Кадила Фармасьютикалз Лтд.
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 Кадила Фармасьютикалз Лтд. (In), Кадила Фармасьютикалз Лтд. filed Critical Кадила Фармасьютикалз Лтд. (In)
Publication of RU2011113690A publication Critical patent/RU2011113690A/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/02—Linear peptides containing at least one abnormal peptide link
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/14—Dipeptidyl-peptidases and tripeptidyl-peptidases (3.4.14)
    • C12Y304/14005—Dipeptidyl-peptidase IV (3.4.14.5)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Abstract

1. Соединение формулы I, ! ! где А представляет собой пептид; ! В представляет собой пептидную связь между пептидом и замещенным амином; ! R1 и R2 такие, как определено здесь, причем R1 и R2 выбраны из водорода, ! , , , ! , , , ! , , , ! , , , ! , , , ! , , . ! n равно от 0 до 10; ! R5, R6, R7 или Ar выбраны из Н или С1-4алкила, групп -CH2CF3, -СН2СН=СН2, -CH2-CON(CH3)2, -Ph, -CH2-Ph, -CH2-(4-MeO-Ph), -CH2-(4-Me-Ph), -CH2-(4-CN-Ph), -CH2-(2-CF3Ph), -CH2-(2-F-Ph), -CH2-(4-F-Ph), -CH(OH)-(4-F-Ph), -CH2-(3,5-бисCF3-Ph), -СН2-(2-пиридил), -2,4-дихлор-Рh, -(4-MeO-Ph), -(4-Me-Ph), -(4-CN-Ph), -(2-Me-Ph), -(2-хлор-Ph), -(2-хлор-4-MeO-Ph), -(2-хлор-4-CN-Ph), -нафтил, -(2-F-Ph), -(2,4-ди-F-Ph), -(2,4,5-ди-F-Ph), ! a, b и с независимо выбраны из N, S, О, С; ! и его фармацевтически приемлемые соли, энантиомеры. ! 2. Соединение по п.1, которое при взаимодействии с ферментом DPP-IV высвобождает вещество, ингибирующее фермент DPP-IV. ! 3. Ингибирование фермента дипептидилпептидазы IV (DPP-IV) у млекопитающего путем введения соединения, заявленного в пп.1 и 2.

Claims (3)

1. Соединение формулы I,
Figure 00000001
где А представляет собой пептид;
В представляет собой пептидную связь между пептидом и замещенным амином;
R1 и R2 такие, как определено здесь, причем R1 и R2 выбраны из водорода,
Figure 00000002
,
Figure 00000003
,
Figure 00000004
,
Figure 00000005
,
Figure 00000006
,
Figure 00000007
,
Figure 00000008
,
Figure 00000009
,
Figure 00000010
,
Figure 00000011
,
Figure 00000012
,
Figure 00000013
,
Figure 00000014
,
Figure 00000015
,
Figure 00000016
,
Figure 00000017
,
Figure 00000018
,
Figure 00000019
.
n равно от 0 до 10;
R5, R6, R7 или Ar выбраны из Н или С1-4алкила, групп -CH2CF3, -СН2СН=СН2, -CH2-CON(CH3)2, -Ph, -CH2-Ph, -CH2-(4-MeO-Ph), -CH2-(4-Me-Ph), -CH2-(4-CN-Ph), -CH2-(2-CF3Ph), -CH2-(2-F-Ph), -CH2-(4-F-Ph), -CH(OH)-(4-F-Ph), -CH2-(3,5-бисCF3-Ph), -СН2-(2-пиридил), -2,4-дихлор-Рh, -(4-MeO-Ph), -(4-Me-Ph), -(4-CN-Ph), -(2-Me-Ph), -(2-хлор-Ph), -(2-хлор-4-MeO-Ph), -(2-хлор-4-CN-Ph), -нафтил, -(2-F-Ph), -(2,4-ди-F-Ph), -(2,4,5-ди-F-Ph),
a, b и с независимо выбраны из N, S, О, С;
и его фармацевтически приемлемые соли, энантиомеры.
2. Соединение по п.1, которое при взаимодействии с ферментом DPP-IV высвобождает вещество, ингибирующее фермент DPP-IV.
3. Ингибирование фермента дипептидилпептидазы IV (DPP-IV) у млекопитающего путем введения соединения, заявленного в пп.1 и 2.
RU2011113690/04A 2008-09-12 2009-09-11 Новые ингибиторы дипептидилпептидазы iv (dp-iv) RU2011113690A (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1934/MUM/2008 2008-09-12
IN1934MU2008 2008-09-12

Publications (1)

Publication Number Publication Date
RU2011113690A true RU2011113690A (ru) 2012-10-20

Family

ID=42004838

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2011113690/04A RU2011113690A (ru) 2008-09-12 2009-09-11 Новые ингибиторы дипептидилпептидазы iv (dp-iv)

Country Status (9)

Country Link
US (2) US8563517B2 (ru)
EP (1) EP2343973B1 (ru)
JP (1) JP5781930B2 (ru)
AU (1) AU2009290531B2 (ru)
CA (1) CA2737253C (ru)
ES (1) ES2571217T3 (ru)
RU (1) RU2011113690A (ru)
WO (1) WO2010029422A1 (ru)
ZA (1) ZA201102597B (ru)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2555617A4 (en) * 2010-04-05 2013-08-14 Cadila Pharmaceuticals Ltd NEW COMPOUNDS FOR THE TREATMENT OF HYPOGLYCEMIA
WO2012017391A2 (en) * 2010-08-03 2012-02-09 Cadila Pharmaceuticals Limited Novel compounds as dpp-iv inhibitors and process for preparation thereof
CN106543141A (zh) * 2015-09-21 2017-03-29 成都苑东生物制药股份有限公司 尿嘧啶衍生物

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL111785A0 (en) * 1993-12-03 1995-01-24 Ferring Bv Dp-iv inhibitors and pharmaceutical compositions containing them
DE19828114A1 (de) * 1998-06-24 2000-01-27 Probiodrug Ges Fuer Arzneim Produgs instabiler Inhibitoren der Dipeptidyl Peptidase IV
DE19828113A1 (de) * 1998-06-24 2000-01-05 Probiodrug Ges Fuer Arzneim Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV
US6613879B1 (en) * 1999-05-14 2003-09-02 Boehringer Ingelheim Pharma Kg FAP-activated anti-tumour compounds
WO2003048190A2 (en) * 2001-12-04 2003-06-12 The Curators Of The University Of Missouri Acyclovir-peptide analogs
JP4491346B2 (ja) * 2002-10-07 2010-06-30 メルク・シャープ・エンド・ドーム・コーポレイション 抗糖尿病ベータアミノ複素環ジペプチジルペプチダーゼ阻害剤
AU2003297219A1 (en) * 2002-12-20 2004-07-22 Merck & Co., Inc. 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
WO2004085661A2 (en) * 2003-03-24 2004-10-07 Merck & Co., Inc Process to chiral beta-amino acid derivatives
GB0310593D0 (en) * 2003-05-08 2003-06-11 Leuven K U Res & Dev Peptidic prodrugs
JO2625B1 (en) 2003-06-24 2011-11-01 ميرك شارب اند دوم كوربوريشن Phosphoric acid salts of dipeptidyl betidase inhibitor 4
AU2004285535A1 (en) * 2003-10-31 2005-05-12 Alza Corporation Compositions and dosage forms for enhanced absorption of gabapentin and pregabalin
US7442682B2 (en) * 2004-10-19 2008-10-28 Nitto Denko Corporation Transepithelial delivery of peptides with incretin hormone activities

Also Published As

Publication number Publication date
AU2009290531A1 (en) 2010-03-18
ES2571217T3 (es) 2016-05-24
EP2343973A1 (en) 2011-07-20
EP2343973B1 (en) 2016-02-17
JP2013504516A (ja) 2013-02-07
US8563517B2 (en) 2013-10-22
CA2737253A1 (en) 2010-03-18
EP2343973A4 (en) 2012-05-23
US20110183919A1 (en) 2011-07-28
WO2010029422A1 (en) 2010-03-18
CA2737253C (en) 2017-08-15
JP5781930B2 (ja) 2015-09-24
ZA201102597B (en) 2011-12-28
US20140045771A1 (en) 2014-02-13
AU2009290531B2 (en) 2014-08-21

Similar Documents

Publication Publication Date Title
EA201170061A1 (ru) Новые производные фенилимидазола в качестве ингибиторов фермента pde10a
PE20120517A1 (es) Inhibidores del virus de la hepatitis c
PE20110300A1 (es) Compuestos de pirrol como inhibidores de la bomba de protones
PE20070540A1 (es) Derivados de pirrol como inhibidores de la secrecion acida
PE20140236A1 (es) IMIDAZO[5,1-f][1,2,4]TRIAZINAS PARA EL TRATAMIENTO DE TRASTORNOS NEUROLOGICOS
EA201170617A1 (ru) Пиразолиламинопиридины в качестве ингибиторов fak
PE20070321A1 (es) Compuestos heterociclicos como inhibidores de proteasas
PE20090109A1 (es) Compuestos pirrolicos como inhidores de la bomba de protones
EA201290518A1 (ru) Производные 2-арилимидазола в качестве ингибиторов фермента pde10a
PE20090048A1 (es) Derivados de glicina n-sustituidos: inhibidores de prolil hidroxilasa
RU2013119129A (ru) Органические соединения
ATE432259T1 (de) Pyridinderivate als dipeptedyl-peptidase-hemmer
EA200800791A1 (ru) Сульфонилпирролгидрохлориды, как ингибиторы гистондезацетилазы
EA201200920A1 (ru) Замещенные изохинолиноны и хинализолиноны
EA200970856A1 (ru) Ингибиторы пути хеджхога
PE20121526A1 (es) Compuestos policiclicos heterociclicos como inhibidores del virus de la hepatitis c
ATE478047T1 (de) Indolderivate als viruzide
GEP20125589B (en) TRIAZINE COMPOUNDS AS P13 KINASE AND mTOR INHIBITORS
NO20080761L (no) Acykliske Ikur inhibitorer
DOP2011000204A (es) Inhibidores de proteina cinasa
JO2732B1 (en) Organic compounds
PE20142185A1 (es) Pirrolidina-2-carboxamidas sustituidas
EA201071173A1 (ru) Применение частиц твёрдого носителя для улучшения технологических характеристик фармацевтического агента
EA201070442A1 (ru) НОВЫЕ ИНГИБИТОРЫ sEH И ИХ ПРИМЕНЕНИЕ
PE20060692A1 (es) Inhibidores bace