WO2017121308A1 - Composés de pyrimidine fusionnés, compositions et procédés d'utilisation - Google Patents

Composés de pyrimidine fusionnés, compositions et procédés d'utilisation Download PDF

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Publication number
WO2017121308A1
WO2017121308A1 PCT/CN2017/070720 CN2017070720W WO2017121308A1 WO 2017121308 A1 WO2017121308 A1 WO 2017121308A1 CN 2017070720 W CN2017070720 W CN 2017070720W WO 2017121308 A1 WO2017121308 A1 WO 2017121308A1
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WO
WIPO (PCT)
Prior art keywords
alkyl
cycloalkyl
independently selected
aryl
heteroaryl
Prior art date
Application number
PCT/CN2017/070720
Other languages
English (en)
Inventor
Xingdong ZHAO
Chuiliang YU
Haohan TAN
Yue RONG
Qihong Liu
Zhifu Li
Bin Liu
Jing Sun
Weibo Wang
Original Assignee
Chongqing Fochon Pharmaceutical Co., Ltd.
Shanghai Fochon Pharmaceutical Co., Ltd.
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 Chongqing Fochon Pharmaceutical Co., Ltd., Shanghai Fochon Pharmaceutical Co., Ltd. filed Critical Chongqing Fochon Pharmaceutical Co., Ltd.
Publication of WO2017121308A1 publication Critical patent/WO2017121308A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • a method to treat, ameliorate or prevent a condition which responds to inhibition of URAT1 comprising administering to a system or subject in need of such treatment an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof, and optionally in combination with a second therapeutic agent, thereby treating said condition.
  • the subject in need of decreased uric acid levels has a disorder characterized by abnormally high content of uric acid in one or more tissues or organs of the subject.
  • the disorder is characterized by over production of uric acid, low excretion of uric acid, tumor lysis, a blood disorder or a combination thereof.
  • the disorder is gout.
  • condition disclosed herein is gout.
  • substituent groups are specified by their conventional chemical formulas, written from left to right, they equally encompass the chemically identical substituents that would result from writing the structure from right to left.
  • CH 2 O is equivalent to OCH 2 .
  • cycloalkylamino refers to cycloalkyl radical that is single bonded to a nitrogen atom. The attachment point of a cycloalkylamino radical to a molecule is through the nitrogen atom.
  • a cycloalkylamino radical may be depicted as -NH (cycloalkyl) .
  • C 3-10 cycloalkylamino refers to a cycloalkylamino radical containing from three to ten carbon atoms. Cycloalkylamino groups, includes but is not limited to, cyclopropylamino, cyclobutylamino, cyclohexylamino, and the like.
  • heteroaryl substituent is bicyclic or tricyclic and at least one ring is non-aromatic or contains no heteroatoms, it is understood that attachment is via the aromatic ring or via the heteroatom containing ring, respectively.
  • substitution of alkyl, cycloalkyl, heterocyclyl, aryl, and/or heteroaryl refers to substitution of each of those groups individually as well as to substitutions of combinations of those groups. That is, if R 1 is arylalkyl, the aryl portion may be unsubstituted or substituted with at least one substituent, such as one, two, three, or four substituents, independently selected from R 6b and the alkyl portion may also be unsubstituted or substituted with at least one substituent, such as one, two, three, or four substituens, independently selected from R 6a .
  • salts may be prepared using a pharmaceutically acceptable non-toxic acid, selected from inorganic and organic acids.
  • acid may be selected, for example, from acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethanesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, malic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, and p-toluenesulfonic acids.
  • such acid may be selected, for example, from citric, hydrobromic, hydrochloric, maleic, phosphoric, sulfuric, fumaric, and tartaric acids.
  • C (O) OH protecting group includes, but not limited to, methyl, ethyl, n-propyl, isopropyl, 1, 1-dimethylpropyl, n-butyl, tert-butyl, phenyl, naphthyl, benzyl, diphenylmethyl, triphenylmethyl, para-nitrobenzyl, para-methoxybenzyl, bis (para-methoxyphenyl) methyl, acetylmethyl, benzoylmethyl, para-nitrobenzoylmethyl, para-bromobenzoylmethyl, para-methanesulfonylbenzoylmethyl, 2-tetrahydropyranyl, 2-tetrahydrofuranyl, 2, 2, 2-trichloro-ethyl, 2- (trimethylsilyl) ethyl, acetoxymethyl, propionyloxymethyl, pivaloyloxymethyl, phthalimidomethyl, succini
  • treat, “ “treating” or “treatment, “ and other grammatical equivalents as used herein, include alleviating, abating or ameliorating a disease or condition, preventing additional symptoms, ameliorating or preventing the underlying metabolic causes of symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition, and are intended to include prophylaxis.
  • the terms further include achieving a therapeutic benefit and/or a prophylactic benefit.
  • therapeutic benefit is meant eradication or amelioration of the underlying disorder being treated.
  • each R c1 and each R d1 are independently selected from hydrogen, halogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 3-10 cycloalkyl, C 3-10 cycloalkyl-C 1-4 alkyl, heterocyclyl, heterocyclyl-C 1-4 alkyl, aryl, aryl-C 1-4 alkyl, heteroaryl, and heteroaryl-C 1-4 alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each unsubstituted or substituted with at least one substituent, such as one, two, three or four substituents, independently selected from R Y ;
  • solutions or suspensions may further comprise viscosity-increasing agents, including but not limited to, sodium carboxymethylcellulose, carboxymethylcellulose, dextran, polyvinylpyrrolidone, gelatins, or solubilizers, e.g. Tween 80 (polyoxyethylene (20) sorbitan mono-oleate) .
  • viscosity-increasing agents including but not limited to, sodium carboxymethylcellulose, carboxymethylcellulose, dextran, polyvinylpyrrolidone, gelatins, or solubilizers, e.g. Tween 80 (polyoxyethylene (20) sorbitan mono-oleate) .
  • compositions for oral administration may be obtained, for example, by combining the active ingredient with one or more solid carriers, and if desired, granulating a resulting mixture, and processing the mixture or granules by the inclusion of additional excipients, to form tablets or tablet cores.
  • Suitable carriers refers to relatively nontoxic chemical compounds or agents that facilitate the incorporation of a compound into cells or tissues, which include but are not limited to fillers, such as sugars, for example lactose, saccharose, mannitol or sorbitol, cellulose preparations, and/or calcium phosphates, for example tricalcium phosphate or calcium hydrogen phosphate, and also binders, such as starches, for example corn, wheat, rice or potato starch, methylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone, and/or, if desired, disintegrators, such as the above-mentioned starches, carboxymethyl starch, crosslinked polyvinylpyrrolidone, alginic acid or a salt thereof, such as sodium alginate. Additional excipients include flow conditioners and lubricants, for example silicic acid, talc, stearic acid or salts thereof, such as magnesium or calcium

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Epidemiology (AREA)

Abstract

L'invention concerne certains inhibiteurs d'URAT1, leurs compositions pharmaceutiques et leurs méthodes d'utilisation.
PCT/CN2017/070720 2016-01-11 2017-01-10 Composés de pyrimidine fusionnés, compositions et procédés d'utilisation WO2017121308A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662277459P 2016-01-11 2016-01-11
US62/277,459 2016-01-11

Publications (1)

Publication Number Publication Date
WO2017121308A1 true WO2017121308A1 (fr) 2017-07-20

Family

ID=59310758

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2017/070720 WO2017121308A1 (fr) 2016-01-11 2017-01-10 Composés de pyrimidine fusionnés, compositions et procédés d'utilisation

Country Status (1)

Country Link
WO (1) WO2017121308A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108659000A (zh) * 2017-05-03 2018-10-16 成都海创药业有限公司 杂环化合物及其制备方法

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1027369C (zh) * 1989-05-16 1995-01-11 默里尔多药物公司 兴奋性氨基酸拮抗剂的制备方法
WO2004074284A1 (fr) * 2003-02-21 2004-09-02 Pfizer Inc. Derives d'oxazole utilises en tant qu'agonistes de ppar
WO2006044821A1 (fr) * 2004-10-19 2006-04-27 Sb Pharmco Puerto Rico Inc. Antagonistes du recepteur du crf et procedes associes
WO2007056281A2 (fr) * 2005-11-03 2007-05-18 Ilypsa, Inc. Composes d'indole multivalents et leur utilisation en tant qu'inhibiteurs de phospholipases a2
CN102143746A (zh) * 2008-07-03 2011-08-03 埃克塞利希斯股份有限公司 Cdk 调节剂
CN103068801B (zh) * 2010-06-16 2014-05-14 亚德生化公司 硫代乙酸盐化合物、组合物及其使用方法
WO2016040419A1 (fr) * 2014-09-11 2016-03-17 Bristol-Myers Squibb Company Inhibiteurs de myéloperoxydase à base de thioéther triazolopyridine et triazolopyrmidine

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1027369C (zh) * 1989-05-16 1995-01-11 默里尔多药物公司 兴奋性氨基酸拮抗剂的制备方法
WO2004074284A1 (fr) * 2003-02-21 2004-09-02 Pfizer Inc. Derives d'oxazole utilises en tant qu'agonistes de ppar
WO2006044821A1 (fr) * 2004-10-19 2006-04-27 Sb Pharmco Puerto Rico Inc. Antagonistes du recepteur du crf et procedes associes
WO2007056281A2 (fr) * 2005-11-03 2007-05-18 Ilypsa, Inc. Composes d'indole multivalents et leur utilisation en tant qu'inhibiteurs de phospholipases a2
CN102143746A (zh) * 2008-07-03 2011-08-03 埃克塞利希斯股份有限公司 Cdk 调节剂
CN103068801B (zh) * 2010-06-16 2014-05-14 亚德生化公司 硫代乙酸盐化合物、组合物及其使用方法
WO2016040419A1 (fr) * 2014-09-11 2016-03-17 Bristol-Myers Squibb Company Inhibiteurs de myéloperoxydase à base de thioéther triazolopyridine et triazolopyrmidine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SAXENA, ABHISHEK S. ET AL.: "A convenient and expeditious synthesis of annulated N, S- heterocycles", JOURNAL OF THE INDIAN CHEMICAL SOCIETY, vol. 80, no. 4, 31 December 2003 (2003-12-31), pages 312, ISSN: 0019-4522 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108659000A (zh) * 2017-05-03 2018-10-16 成都海创药业有限公司 杂环化合物及其制备方法
WO2018202039A1 (fr) * 2017-05-03 2018-11-08 成都海创药业有限公司 Composé hétérocyclique et son procédé de préparation

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