PE20230827A1 - [1,3]DIAZINO[5,4-d]PIRIMIDINAS COMO INHIBIDORES DE HER2 - Google Patents

[1,3]DIAZINO[5,4-d]PIRIMIDINAS COMO INHIBIDORES DE HER2

Info

Publication number
PE20230827A1
PE20230827A1 PE2022002443A PE2022002443A PE20230827A1 PE 20230827 A1 PE20230827 A1 PE 20230827A1 PE 2022002443 A PE2022002443 A PE 2022002443A PE 2022002443 A PE2022002443 A PE 2022002443A PE 20230827 A1 PE20230827 A1 PE 20230827A1
Authority
PE
Peru
Prior art keywords
diazino
pyrimidines
atom
her2
halogen
Prior art date
Application number
PE2022002443A
Other languages
English (en)
Spanish (es)
Inventor
Birgit Wilding
Dietrich Boese
Harald Engelhardt
Julian Fuchs
Ralph Neumueller
Mark Petronczki
Dirk Scharn
Matthias Treu
Original Assignee
Boehringer Ingelheim Int
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 Boehringer Ingelheim Int filed Critical Boehringer Ingelheim Int
Publication of PE20230827A1 publication Critical patent/PE20230827A1/es

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-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
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • 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)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Biochemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
PE2022002443A 2020-04-24 2021-04-07 [1,3]DIAZINO[5,4-d]PIRIMIDINAS COMO INHIBIDORES DE HER2 PE20230827A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP20171221 2020-04-24
PCT/EP2021/059015 WO2021213800A1 (en) 2020-04-24 2021-04-07 [1,3]DIAZINO[5,4-d]PYRIMIDINES AS HER2 INHIBITORS

Publications (1)

Publication Number Publication Date
PE20230827A1 true PE20230827A1 (es) 2023-05-19

Family

ID=70470818

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2022002443A PE20230827A1 (es) 2020-04-24 2021-04-07 [1,3]DIAZINO[5,4-d]PIRIMIDINAS COMO INHIBIDORES DE HER2

Country Status (33)

Country Link
US (3) US11608343B2 (enExample)
EP (2) EP4139309B9 (enExample)
JP (2) JP7260723B2 (enExample)
KR (2) KR102759974B1 (enExample)
CN (13) CN118388490A (enExample)
AR (1) AR121779A1 (enExample)
AU (1) AU2021260721A1 (enExample)
CA (1) CA3173602A1 (enExample)
CL (1) CL2022002579A1 (enExample)
CO (1) CO2022015054A2 (enExample)
CR (1) CR20220537A (enExample)
DK (1) DK4139309T5 (enExample)
DO (1) DOP2022000189A (enExample)
EC (1) ECSP22072777A (enExample)
ES (1) ES3013860T3 (enExample)
FI (1) FI4139309T3 (enExample)
HR (1) HRP20250426T1 (enExample)
HU (1) HUE070805T2 (enExample)
IL (2) IL297490B2 (enExample)
JO (1) JOP20220271A1 (enExample)
LT (1) LT4139309T (enExample)
MA (1) MA59373B1 (enExample)
MX (1) MX2022013223A (enExample)
PE (1) PE20230827A1 (enExample)
PH (1) PH12022552745A1 (enExample)
PL (1) PL4139309T3 (enExample)
PT (1) PT4139309T (enExample)
RS (1) RS66557B1 (enExample)
SI (1) SI4139309T1 (enExample)
SM (1) SMT202500164T1 (enExample)
TW (1) TWI913256B (enExample)
UA (1) UA130588C2 (enExample)
WO (1) WO2021213800A1 (enExample)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119390683A (zh) 2019-08-15 2025-02-07 黑钻治疗公司 炔基喹唑啉化合物
US20230126204A1 (en) * 2020-02-03 2023-04-27 Boehringer Ingelheim International Gmbh [1,3]DIAZINO[5,4-d]PYRIMIDINES AS HER2 INHIBITORS
US11608343B2 (en) 2020-04-24 2023-03-21 Boehringer Ingelheim International Gmbh Substituted pyrimido[5,4-d]pyrimidines as HER2 inhibitors
TW202214641A (zh) 2020-06-30 2022-04-16 美商艾瑞生藥股份有限公司 Her2突變抑制劑
CA3213079A1 (en) 2021-04-13 2022-10-20 Kristin Lynne ANDREWS Amino-substituted heterocycles for treating cancers with egfr mutations
WO2022266458A1 (en) * 2021-06-17 2022-12-22 Black Diamond Therapeutics, Inc. 6-heterocycloalkyl-quinazoline derivatives and uses thereof
JP7511097B1 (ja) 2021-06-26 2024-07-04 アレイ バイオファーマ インコーポレイテッド Her2変異阻害薬
US20250136595A1 (en) * 2022-02-09 2025-05-01 Enliven Inc. Acylated heterocyclic quinazoline derivatives as inhibitors of erbb2
JP2025509995A (ja) 2022-03-28 2025-04-11 江蘇恒瑞医薬股▲ふん▼有限公司 含窒素複素環系化合物、その調製方法及びその医薬的使用
KR102854653B1 (ko) * 2022-04-05 2025-09-04 보로노이 주식회사 헤테로아릴 유도체 및 이의 용도
CN117384162A (zh) * 2022-05-17 2024-01-12 浙江文达医药科技有限公司 选择性her2抑制剂
WO2024027695A1 (zh) * 2022-08-04 2024-02-08 微境生物医药科技(上海)有限公司 作为her2抑制剂的化合物
US20240132521A1 (en) 2022-08-22 2024-04-25 Iambic Therapeutics, Inc. Compounds and methods for modulating her2
KR20250133319A (ko) 2022-12-22 2025-09-05 베링거 인겔하임 인터내셔날 게엠베하 Her2 억제제의 결정형
MX2025007174A (es) 2022-12-22 2025-07-01 Boehringer Ingelheim Int Dispersion solida de un inhibidor de her2
CN120456906A (zh) 2022-12-22 2025-08-08 勃林格殷格翰国际有限公司 Her2抑制剂的固体分散体的给药安排方案
AU2024247020A1 (en) 2023-03-29 2025-10-30 Boehringer Ingelheim International Gmbh Dosing schedule of a her2 inhibitor
AU2024241633A1 (en) 2023-03-30 2025-11-06 Revolution Medicines, Inc. Compositions for inducing ras gtp hydrolysis and uses thereof
CN121712509A (zh) 2023-05-04 2026-03-20 锐新医药公司 用于ras相关疾病或病症的组合疗法
WO2024246114A1 (en) 2023-05-31 2024-12-05 Boehringer Ingelheim International Gmbh Survivin as a biomarker for predicting the responsiveness of cancer treatment
CN116903615A (zh) * 2023-06-21 2023-10-20 江苏丽源医药有限公司 一种妥卡替尼及其中间体的制备方法
KR20260059568A (ko) 2023-07-28 2026-04-30 베링거 인겔하임 인터내셔날 게엠베하 Her2 억제제의 제조 방법
US20250049810A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
CN121729231A (zh) * 2023-09-06 2026-03-24 勃林格殷格翰国际有限公司 用HER2抑制剂和CYP3A和/或P-gp调节剂进行的癌症治疗
IL327306A (en) 2023-10-12 2026-05-01 Revolution Medicines Inc Macrocyclic RAS inhibitors
US20250205238A1 (en) 2023-12-20 2025-06-26 Boehringer Ingelheim International Gmbh Anti-cancer combination therapy
US20250228858A1 (en) 2023-12-20 2025-07-17 Boehringer Ingelheim International Gmbh Anti-cancer combination therapy
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
WO2025210042A1 (en) * 2024-04-03 2025-10-09 Boehringer Ingelheim International Gmbh Combination of zongertinib with a sos1 inhibitor for use in the treatment of cancer
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
WO2025255438A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025257149A1 (en) 2024-06-11 2025-12-18 Boehringer Ingelheim International Gmbh Crystalline forms of zongertinib a her2 tyrosine kinase inhibitor
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en) 2024-06-28 2026-01-02 Revolution Medicines, Inc. Ras inhibitors
WO2026007878A1 (zh) * 2024-07-01 2026-01-08 北京鞍石生物科技股份有限公司 稠环化合物及其制备方法和应用
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026027757A1 (en) 2024-08-02 2026-02-05 Boehringer Ingelheim International Gmbh Treatment of cancer with metastases in the central nervous system
WO2026050446A1 (en) 2024-08-29 2026-03-05 Revolution Medicines, Inc. Ras inhibitors
WO2026072904A2 (en) 2024-09-26 2026-04-02 Revolution Medicines, Inc. Compositions and methods for treating lung cancer
WO2026077844A1 (en) 2024-10-07 2026-04-16 Boehringer Ingelheim International Gmbh Solid dispersions having stabilized emulsion particles
WO2026090116A2 (en) 2024-10-21 2026-04-30 Revolution Medicines, Inc. Ras inhibitors
WO2026090245A1 (en) 2024-10-22 2026-04-30 Revolution Medicines, Inc. Use of ras inhibitors for treating cancer
US20260108528A1 (en) 2024-10-22 2026-04-23 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW414798B (en) * 1994-09-07 2000-12-11 Thomae Gmbh Dr K Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation
DE19608588A1 (de) 1996-03-06 1997-09-11 Thomae Gmbh Dr K Pyrimido [5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
IL161908A0 (en) 2001-12-12 2005-11-20 Pfizer Prod Inc Quinazoline derivatives for the treatment of abnormal cell growth
JP2007510708A (ja) 2003-11-06 2007-04-26 ファイザー・プロダクツ・インク 癌の治療における選択的erbB2阻害剤/抗erbB抗体の組合せ
CA2755268C (en) 2005-11-15 2013-12-31 Array Biopharma, Inc. Erbb inhibitors
WO2007059217A2 (en) * 2005-11-16 2007-05-24 Lonnie Lehrer Automobile propulsion system
JP6468611B2 (ja) 2014-05-13 2019-02-13 アリアド ファーマシューティカルズ, インコーポレイテッド キナーゼ阻害のためのヘテロアリール化合物
MY186839A (en) 2014-06-19 2021-08-25 Takeda Pharmaceuticals Co Heteroaryl compounds for kinase inhibition
JP6863901B2 (ja) 2015-05-13 2021-04-28 アリアド ファーマシューティカルズ, インコーポレイテッド キナーゼ阻害のためのヘテロアリール化合物
EP3676267A4 (en) 2017-08-31 2021-04-14 Dana Farber Cancer Institute, Inc. EGFR AND / OR HER2 INHIBITORS AND METHODS OF USE
CN109422755B (zh) 2017-09-01 2023-07-04 上海医药集团股份有限公司 一种含氮杂环化合物、制备方法、中间体、组合物和应用
US20230126204A1 (en) 2020-02-03 2023-04-27 Boehringer Ingelheim International Gmbh [1,3]DIAZINO[5,4-d]PYRIMIDINES AS HER2 INHIBITORS
WO2021156180A1 (en) 2020-02-03 2021-08-12 Boehringer Ingelheim International Gmbh [1,3]diazino[5,4-d]pyrimidines as her2 inhibitors
US11608343B2 (en) 2020-04-24 2023-03-21 Boehringer Ingelheim International Gmbh Substituted pyrimido[5,4-d]pyrimidines as HER2 inhibitors
WO2021231400A1 (en) 2020-05-12 2021-11-18 Accutar Biotechnology, Inc. Bis-aryl ethers containing n-acyl azetidine as egfr/her2 inhibitors

Also Published As

Publication number Publication date
TWI913256B (zh) 2026-02-01
ECSP22072777A (es) 2022-10-31
AU2021260721A1 (en) 2022-09-15
FI4139309T3 (fi) 2025-03-04
CN118388493A (zh) 2024-07-26
CN118388491A (zh) 2024-07-26
CN118388494A (zh) 2024-07-26
CA3173602A1 (en) 2021-10-28
CR20220537A (es) 2022-12-06
CN118388495A (zh) 2024-07-26
JP7260723B2 (ja) 2023-04-18
MX2022013223A (es) 2022-11-14
CN118307543A (zh) 2024-07-09
PT4139309T (pt) 2025-02-17
US20250122204A1 (en) 2025-04-17
KR102759974B1 (ko) 2025-01-24
DK4139309T3 (da) 2025-04-28
UA130588C2 (uk) 2026-03-25
CN118307544A (zh) 2024-07-09
SMT202500164T1 (it) 2025-05-12
IL320477A (en) 2025-06-01
US20230374021A1 (en) 2023-11-23
CO2022015054A2 (es) 2023-02-16
TW202206432A (zh) 2022-02-16
MA59373B1 (fr) 2025-02-28
EP4139309B1 (en) 2025-01-29
IL297490B2 (en) 2025-10-01
AR121779A1 (es) 2022-07-06
WO2021213800A1 (en) 2021-10-28
CN118388489A (zh) 2024-07-26
SI4139309T1 (sl) 2025-03-31
KR20230005263A (ko) 2023-01-09
US20210332054A1 (en) 2021-10-28
DK4139309T5 (da) 2025-10-27
KR20250016507A (ko) 2025-02-03
JP2023512343A (ja) 2023-03-24
JOP20220271A1 (ar) 2021-10-28
BR112022021514A2 (pt) 2023-01-24
DOP2022000189A (es) 2022-09-30
LT4139309T (lt) 2025-02-25
RS66557B1 (sr) 2025-03-31
US11608343B2 (en) 2023-03-21
IL297490A (en) 2022-12-01
ES3013860T3 (en) 2025-04-15
CN115485277A (zh) 2022-12-16
HUE070805T2 (hu) 2025-07-28
CN118388492A (zh) 2024-07-26
EP4566611A2 (en) 2025-06-11
CN118388488A (zh) 2024-07-26
EP4139309B9 (en) 2025-09-10
EP4566611A3 (en) 2025-09-10
IL297490B1 (en) 2025-06-01
HRP20250426T1 (hr) 2025-06-06
PL4139309T3 (pl) 2025-05-05
CN118619956A (zh) 2024-09-10
PH12022552745A1 (en) 2024-03-25
CN118388487A (zh) 2024-07-26
ES3013860T9 (en) 2025-10-28
CN118388490A (zh) 2024-07-26
JP2023085489A (ja) 2023-06-20
CN115485277B (zh) 2024-05-14
CL2022002579A1 (es) 2023-05-19
EP4139309A1 (en) 2023-03-01

Similar Documents

Publication Publication Date Title
PE20220592A1 (es) Inhibidores de la autofagia de heteroarilaminopirimidina amida y metodos de uso de estos
PH12021551065A1 (en) Fused ring compounds
AR121779A1 (es) [1,3]DIAZINO[5,4-d]PIRIMIDINAS COMO INHIBIDORES DE HER2
CR20210083A (es) Compuestos de anillo fusionado
CY1124404T1 (el) Παραγωγα χολικου οξεος ως αγωνιστες fxr/tgr5 και μεθοδοι χρησης αυτων
PE20211655A1 (es) Compuestos de 6-azabencimidazol sustituidos como inhibidores de hpk1
PE20211089A1 (es) Nuevos compuestos heterociclicos como inhibidores de la monoacilglicerol lipasa
PE20242005A1 (es) Derivados espirociclicos de piperidinilo como inhibidores del factor b del complemento y usos de los mismos
AR096339A1 (es) Agonistas del receptor de somatostatina subtipo 4 (sstr4)
UY37795A (es) Sulfonilureas y sulfoniltioureas útiles como inhibidores de nlrp3
PE20190705A1 (es) COMPUESTOS DE BENZO[b] TIOFENO COMO AGONISTAS DE STING
PE20040927A1 (es) Derivados de 1-propanolol y 1-propilamina, como ligandos de receptores de glucocorticoides
AR077935A1 (es) Derivados de 3-amino-5 fenil-5,6-dihidro-2h-(1,4)oxazina
AR104259A1 (es) Inhibidores de bromodominio
PE20041016A1 (es) Derivados de pirimidina para el tratamiento del crecimiento celular anormal
PE20181197A1 (es) 2,4-dihidroxi-nicotinamidas como agonistas del receptor de apelina (apj)
BR112022005674A2 (pt) Derivado de anel fundido aromático substituído e composição compreendendo o mesmo, e uso do mesmo
CL2023002635A1 (es) Derivados de 3h,4h,5h,6h,7h-pirimido[4,5-b][1,4]oxazin-4,6-diona como inhibidores de trpa1
PE20160691A1 (es) Nuevos derivados de triazolo[4,5-d]pirimidina
PE20220967A1 (es) [1,2,4] triazolo [1,5-c] quinazolin-5-aminas
SA523441335B1 (ar) cGAS مركبات وتركيبات لعلاج حالات مرضية مرتبطة بـ
PE20211390A1 (es) Compuestos antibacterianos
MX381482B (es) Compuestos de tiazin-2-amina fusionados con ciclopropilo como inhibidores de beta-secretasa y metodos de uso.
EA202190272A1 (ru) Дополнительно замещенные производные триазолохиноксалина
CY1124346T1 (el) ΠΑΡΑΓΩΓΑ ΧΡΩΜΑΝΙΟΥ, ΙΣΟΧΡΩΜΑΝΙΟΥ ΚΑΙ ΔΙΥΔΡΟΪΣΟΒΕΝΖΟΦΟΥΡΑΝΙΟΥ ΩΣ mGluR2-APNHTIKOI ΑΛΛΟΣΤΕΡΙΚΟΙ ΔΙΑΜΟΡΦΩΤΕΣ, ΣΥΝΘΕΣΕΙΣ, ΚΑΙ ΧΡΗΣΗ ΑΥΤΩΝ