SI3059239T1 - SULFURIC CONTAINING BICYCLIC COMPOUNDS - Google Patents

SULFURIC CONTAINING BICYCLIC COMPOUNDS Download PDF

Info

Publication number
SI3059239T1
SI3059239T1 SI201430780T SI201430780T SI3059239T1 SI 3059239 T1 SI3059239 T1 SI 3059239T1 SI 201430780 T SI201430780 T SI 201430780T SI 201430780 T SI201430780 T SI 201430780T SI 3059239 T1 SI3059239 T1 SI 3059239T1
Authority
SI
Slovenia
Prior art keywords
compound
salt
dimethylcyclohexyl
methyl
group
Prior art date
Application number
SI201430780T
Other languages
English (en)
Slovenian (sl)
Inventor
Nobuyuki Shiraishi
Hiroaki Hoshii
Wataru Hamaguchi
Eriko Honjo
Tomofumi Takuwa
Yuji Kondo
Takayuki Goto
Original Assignee
Astellas Pharma 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 Astellas Pharma Inc. filed Critical Astellas Pharma Inc.
Publication of SI3059239T1 publication Critical patent/SI3059239T1/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02Heterocyclic 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
    • C07D495/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5355Non-condensed oxazines and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541Non-condensed thiazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/554Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32Alcohol-abuse
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02Heterocyclic 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
    • C07D495/08Bridged systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02Heterocyclic 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
    • C07D495/10Spiro-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Addiction (AREA)
  • Hospice & Palliative Care (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
SI201430780T 2013-10-17 2014-10-17 SULFURIC CONTAINING BICYCLIC COMPOUNDS SI3059239T1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2013216332 2013-10-17
EP14853825.9A EP3059239B1 (en) 2013-10-17 2014-10-17 Sulfur-containing bicyclic compound
PCT/JP2014/077653 WO2015056771A1 (ja) 2013-10-17 2014-10-17 含硫黄二環式化合物

Publications (1)

Publication Number Publication Date
SI3059239T1 true SI3059239T1 (en) 2018-08-31

Family

ID=52826697

Family Applications (1)

Application Number Title Priority Date Filing Date
SI201430780T SI3059239T1 (en) 2013-10-17 2014-10-17 SULFURIC CONTAINING BICYCLIC COMPOUNDS

Country Status (31)

Country Link
US (2) US9051339B2 (enExample)
EP (1) EP3059239B1 (enExample)
JP (1) JP6477484B2 (enExample)
KR (1) KR102248450B1 (enExample)
CN (1) CN105636965B (enExample)
AR (1) AR098070A1 (enExample)
AU (1) AU2014335304B2 (enExample)
BR (1) BR112016008654B8 (enExample)
CA (1) CA2927518C (enExample)
CY (1) CY1120880T1 (enExample)
DK (1) DK3059239T3 (enExample)
EA (1) EA029075B1 (enExample)
ES (1) ES2685070T3 (enExample)
HR (1) HRP20181183T1 (enExample)
HU (1) HUE040208T2 (enExample)
IL (1) IL244953B (enExample)
LT (1) LT3059239T (enExample)
MX (1) MX367857B (enExample)
MY (1) MY177271A (enExample)
NZ (1) NZ719149A (enExample)
PH (1) PH12016500625B1 (enExample)
PL (1) PL3059239T3 (enExample)
PT (1) PT3059239T (enExample)
RS (1) RS57532B1 (enExample)
SA (1) SA516370956B1 (enExample)
SG (1) SG11201602926UA (enExample)
SI (1) SI3059239T1 (enExample)
SM (1) SMT201800431T1 (enExample)
TW (1) TWI648281B (enExample)
UA (1) UA116042C2 (enExample)
WO (1) WO2015056771A1 (enExample)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU231058B1 (hu) 2017-03-13 2020-04-28 Richter Gedeon Nyrt. Gyógyászatilag hatékony aliciklusos-szubsztituált pirazolo[1,5-a]pirimidin származékok
WO2019155765A1 (ja) 2018-02-06 2019-08-15 株式会社瑞光 伸縮シート及び伸縮シートを用いた使い捨て着用物品、並びにそれらの製造方法
MX2021002385A (es) * 2018-08-31 2021-04-29 Astellas Pharma Inc Composicion farmaceutica para administracion oral.
WO2022029666A1 (en) 2020-08-05 2022-02-10 Richter Gedeon Nyrt. PHARMACOLOGICALLY ACTIVE HETEROCYCLIC-SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES
WO2023028519A2 (en) * 2021-08-27 2023-03-02 Astellas Pharma Global Development, Inc. Methods of treating substance use disorder
JP2025157626A (ja) * 2022-09-01 2025-10-16 アステラス製薬株式会社 6-(4,4-ジメチルシクロヘキシル)-4-[(1,1-ジオキソ-1λ6-チオモルホリン-4-イル)メチル]-2-メチルチエノ[2,3-d]ピリミジンまたはその塩の製造方法
WO2024217531A1 (zh) * 2023-04-21 2024-10-24 西藏海思科制药有限公司 Cyp11a1抑制剂及其用途
CN117263951A (zh) * 2023-09-13 2023-12-22 广东莱佛士制药技术有限公司 6-溴-2-甲基噻吩并[2,3-d]嘧啶-4-甲腈的合成方法

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001097979A (ja) 1999-07-28 2001-04-10 Takeda Chem Ind Ltd 縮合複素環化合物、その製造法および用途
WO2002062803A1 (en) 2001-02-08 2002-08-15 Yamanouchi Pharmaceutical Co., Ltd. Thienopyrimidine derivative
JP2002308882A (ja) * 2001-02-08 2002-10-23 Yamanouchi Pharmaceut Co Ltd チエノピリミジン誘導体
WO2004089312A2 (en) * 2003-03-31 2004-10-21 Predix Pharmaceuticals Holdings, Inc. New piperidinylamino-thieno[2,3-d] pyrimidine compounds
US7723324B2 (en) * 2003-10-28 2010-05-25 Sepracor, Inc. Imidazo[1,2-A]pyridine anxiolytics
GB0416168D0 (en) 2004-07-20 2004-08-18 Vernalis Cambridge Ltd Pyrmidothiophene compounds
GB0420719D0 (en) * 2004-09-17 2004-10-20 Addex Pharmaceuticals Sa Novel allosteric modulators
EP1828199B1 (en) * 2004-12-17 2009-05-06 F. Hoffmann-Roche AG Thieno-pyridine derivatives as gaba-b allosteric enhancers
US8802670B2 (en) 2006-04-26 2014-08-12 F. Hoffmann-La Roche Ag Pharmaceutical compounds
ES2665277T3 (es) 2009-03-13 2018-04-25 Katholieke Universiteit Leuven K.U. Leuven R&D Análogos de purina y su uso como agentes inmunosupresores
CA2773131C (en) * 2009-09-04 2015-07-14 The Regents Of The University Of Michigan Compositions and methods for treatment of leukemia
GB201015411D0 (en) 2010-09-15 2010-10-27 Univ Leuven Kath Anti-cancer activity of novel bicyclic heterocycles

Also Published As

Publication number Publication date
CN105636965A (zh) 2016-06-01
US9051339B2 (en) 2015-06-09
PT3059239T (pt) 2018-10-09
CA2927518C (en) 2022-04-12
UA116042C2 (uk) 2018-01-25
ES2685070T3 (es) 2018-10-05
EP3059239B1 (en) 2018-06-27
BR112016008654B8 (pt) 2023-02-14
HK1220192A1 (zh) 2017-04-28
BR112016008654A2 (enExample) 2017-08-01
CA2927518A1 (en) 2015-04-23
US20150231138A1 (en) 2015-08-20
NZ719149A (en) 2019-09-27
JPWO2015056771A1 (ja) 2017-03-09
AU2014335304B2 (en) 2018-03-01
IL244953B (en) 2019-01-31
TWI648281B (zh) 2019-01-21
HUE040208T2 (hu) 2019-02-28
PL3059239T3 (pl) 2018-10-31
SG11201602926UA (en) 2016-05-30
PH12016500625A1 (en) 2016-05-23
KR20160071408A (ko) 2016-06-21
RS57532B1 (sr) 2018-10-31
IL244953A0 (en) 2016-05-31
EA029075B1 (ru) 2018-02-28
HRP20181183T1 (hr) 2018-10-19
MY177271A (en) 2020-09-10
DK3059239T3 (en) 2018-08-13
BR112016008654B1 (pt) 2022-12-06
SMT201800431T1 (it) 2018-09-13
LT3059239T (lt) 2018-09-10
EP3059239A1 (en) 2016-08-24
CN105636965B (zh) 2017-11-24
AR098070A1 (es) 2016-04-27
TW201607951A (zh) 2016-03-01
EP3059239A4 (en) 2017-04-26
EA201690790A1 (ru) 2016-08-31
SA516370956B1 (ar) 2019-04-04
US9642852B2 (en) 2017-05-09
MX367857B (es) 2019-09-09
WO2015056771A1 (ja) 2015-04-23
PH12016500625B1 (en) 2016-05-23
JP6477484B2 (ja) 2019-03-06
CY1120880T1 (el) 2020-05-29
MX2016004944A (es) 2016-07-11
KR102248450B1 (ko) 2021-05-06
US20150111876A1 (en) 2015-04-23

Similar Documents

Publication Publication Date Title
SI3059239T1 (en) SULFURIC CONTAINING BICYCLIC COMPOUNDS
PH12015500347A1 (en) 6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection
EA201491362A1 (ru) Анестезирующие соединения и способы их применения
MD4602B1 (ro) Inhibitori ai virusului hepatic C
MX351581B (es) Nuevos derivados tienopirimidina, un proceso para su preparación y composiciones farmacéuticas que los contienen.
NZ631762A (en) 5-membered heteroaryls and their use as antiviral agents
MD20150092A2 (ro) Derivate ale amidelor pentru tratamentul infecţiei cu HIV
MX2014001481A (es) Compuestos para el tratamiento y profilaxis de la enfermedad del virus sincicial respiratorio.
AR084824A1 (es) Procesos para preparar isoquinolinonas y formas solidas de isoquinolinonas
PE20160204A1 (es) Compuestos y composiciones como inhibidores de la mek
SI2738156T1 (en) TETRACYCLINE COMPOSITE SUBSTITUTED WITH 9-AMINOMETHYL
AR086100A1 (es) Compuestos de cromenona y composiciones farmaceuticas que los contienen
MD20150075A2 (ro) Compuşi tetraciclici heterociclu-substituiţi şi metode de utilizare a acestora pentru tratamentul bolilor virale
MY170262A (en) Dicarboxylic acid compound
AR105774A1 (es) Procedimiento para la preparación de (4s)-4-(4-ciano-2-metoxifenilo)-5-etoxi-2,8-dimetilo-1,4-dihidro-1,6-naftiridina-3-carboxamida y su purificación para su uso como principio activo farmacéutico
IN2014MN01521A (enExample)
PH12014502180A1 (en) Novel thienopyrimidine derivatives, processes for the preparation thereof and therapeutic uses thereof
PE20141553A1 (es) Compuestos de triazolopiridina como inhibidores de la ped10a
PH12015500009B1 (en) Phenoxyethyl piperidine compounds
MX2016005993A (es) Anfifilos biscationicos y triscationicos como agentes antimicrobianos.
PH12017501652A1 (en) Kv1.3 inhibitors and their medical application
MX348979B (es) Agente de control de enfermedades de las plantas.
PE20141168A1 (es) Derivados de pirazolidin-3-ona
EA201600323A1 (ru) Производные пиперазина и их применение в качестве лекарственного средства
BR112016006865A2 (pt) berberinas substituídas e suas sínteses