WO2010108251A2 - Complexo molecular antineoplásico-testosterona - Google Patents

Complexo molecular antineoplásico-testosterona Download PDF

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Publication number
WO2010108251A2
WO2010108251A2 PCT/BR2010/000161 BR2010000161W WO2010108251A2 WO 2010108251 A2 WO2010108251 A2 WO 2010108251A2 BR 2010000161 W BR2010000161 W BR 2010000161W WO 2010108251 A2 WO2010108251 A2 WO 2010108251A2
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Prior art keywords
testosterone
molecular
drug
antineoplastic
molecular complex
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PCT/BR2010/000161
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English (en)
French (fr)
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WO2010108251A3 (pt
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Gerson Silva Paiva
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Universidade Federal de Pernambuco UFPE
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Universidade Federal de Pernambuco UFPE
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K47/54—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 an organic compound
    • A61K47/55—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 an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
    • 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
    • A61K47/54—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 an organic compound
    • A61K47/554—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 an organic compound the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis

Definitions

  • the present invention relates to "ANTEINEOPLASTIC-TESTOSTERONE MOLECULAR COMPLEX", or more particularly to a molecular compound capable of selectively acting on prostate cancer without damaging healthy cells.
  • Prostate cancer is the most frequently diagnosed and the second leading cause of cancer death in men worldwide.
  • Three methods of androgen deprivation are currently used in the palliative treatment of metastatic prostate cancer: 1) surgical castration by orchiectomy to remove primary androgen-producing organs; 2) clinical castration by estrogen therapy or LHRH (LH release hormone) to reduce LH (luteinizing hormone) production; 3) antiandrogen therapy directed primarily at target organs (ie prostate and metastatic points).
  • the purpose of the present invention is to propose a way of destroying metastatic prostate cancer (the one that spreads from the prostate to other androgen-dependent organs such as the testes and seminiferous tubules) using androgen itself as antineoplastic carrier (in this case, adriamycin, a proven anti-cancer drug to treat various cancers). It is a way of "fooling" the tumor, thus allowing the drug to "dribble” the MDR (multidrug resistance) process and to selectively target organs, since prostate cancer needs a lot of testosterone to get rid of it. develop.
  • antineoplastic carrier in this case, adriamycin, a proven anti-cancer drug to treat various cancers.
  • Figure 1 represents the structure of the molecular complexes that make up the antineoplastic-testosterone molecular complex
  • Figure 2 represents the structures of the molecular subunits that make up the antineoplastic-testosterone molecular complex
  • "ANTEINEOPLASTIC MOLECULAR COMPLEX-TESTOSTERONE” consists of a testosterone (1) molecular chain chemically linked to a commercial anti-neoplastic drug, such as daunorubicin or doxorubicin (2), cisplatin (3), carboplatin (4) or cisplatin-berenyl (5) by means of a carbamate-type molecular bridge (6).
  • the present compound is characterized in that it is based on a testosterone molecule (1) chemically bonded to a commercial antineopsy drug (2, 3, 4, 5) by means of a carbamate bridge (6).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Oncology (AREA)
  • Botany (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

A presente invenção trata de um Complexo Molecular Antineoplásico-Testosterona composto de uma cadeia molecular de testosterona (1), um fármaco antineoplásico e uma ponte molecular ou uma molécula. O presente composto está caracterizado por ser baseado em uma molécula de testosterona (1) unida químicamente a um fármaco antineoplásico comercial, como a daunorrubicina ou doxorrubicina (2), cisplatina (3), carboplatina (4) ou cisplatina-berenil (5) por meio de uma ponte molecular do tipo carbamato (6) ou por uma molécula de N'.N-disuccnimidil-carbonato (7). O complexo molecular é uma forma de "guiar" o fármaco anticáncer diretamente ao tumor, permitindo assim que o mesmo atue de forma seletiva na próstata, evitando assim efeitos em tecidos sadios uma vez que este tipo de cáncer necessita de muita testosterona para se desenvolver.

Description

COMPLEXO MOLECULAR ANTINEOPLÁSICO-TESTOSTERONA
A presente Patente de Invenção refere-se a "COMPLEXO MOLECULAR ANTINEOPLÁSICO-TESTOSTERONA", ou mais particularmente a um composto molecular capaz de atuar seletivamente no câncer de próstata sem danificar as células sadias.
O câncer de próstata é o mais frequentemente diagnosticado e a segunda causa de óbito por câncer em homens no mundo. Atualmente são usados três métodos de privação androgênica no tratamento paliativo de câncer de próstata metastático: 1) castração cirúrgica por orquiectomia para remover os órgãos produtores primários de andrógenos; 2) castração clínica por terapia com estrogênio ou LHRH (hormônio de liberação de LH) para reduzir a produção de LH (hormônio luteinizante); 3) terapia antiandrogênica direcionada primariamente aos órgãos-alvos (ou seja, próstata e pontos metastáticos).
Por outro lado, os andrógenos (classe de moléculas, que incluem a testosterona e a progesterona, produzidas pelos testículos, ovários e glândulas supra-renais) entram em suas células-alvos por difusão passiva, existindo evidências de que certos tumores, como os de próstasta, possuem mecanismos que facilitam ou ativam o transporte de andrógenos. Por isso são chamados tumores dependentes de andrógenos.
Portanto, o objetivo da presente Patente de Invenção é propor uma forma de destruir o câncer de próstata metástico (aquele que se espalha, a partir da próstata, para outros órgãos dependentes de andrógenos, como os testículos e túbulos seminíferos) usando o próprio andrógeno como carreador do antineoplásico (no presente caso, a adriamicina, um fármaco anti-câncer comprovadamente eficaz no tratamento de vários tipos de cânceres). É uma forma de "enganar" o tumor, permitindo assim que o fármaco "drible" o processo MDR (de resistência multidroga) e atue de forma seletiva nos órgãos- alvos, uma vez que o câncer de próstata se necessita de muita testosterona para se desenvolver.
Para uma melhor compreensão do presente fármaco é feita a seguir uma descrição detalhada do mesmo, fazendo-se referência aos desenhos anexos, onde a: Figura 1 representa a estrutura dos complexos moleculares que compõem o complexo molecular antineoplásico-testosterona;
Figura 2 representa as estruturas das subunidades moleculares que compõem o complexo molecular antineoplásico-testosterona;
De acordo com estas ilustrações e em seus pormenores, mais particularmente as figuras 1 e 2 a presente Patente de Invenção, "COMPLEXO MOLECULAR ANTINEOPLÁSICO-TESTOSTERONA" consta de uma cadeia molecular de testosterona (1) ligada quimicamente a um fármaco antineopiásico comercial, como a daunorrubicina ou doxorrubicina (2), cisplatina (3), carboplatina (4) ou cisplatina-berenil (5) por meio de uma ponte molecular do tipo carbamato (6) . O presente composto está caracterizado por ser baseado em uma molécula de testosterona (1) unida quimicamente a um fármaco antineopiásico comercial (2, 3, 4, 5) por meio de uma ponte carbamato (6).
Como se percebe após o que foi exposto e ilustrado, trata-se de um complexo molecular capaz de combater preferencialmente o câncer de próstata devido ao fato de o fármaco antineopiásico (de uso comercial) estar ligado a um hormônio, a testosterona, este último sendo o alimento do câncer e o carreador do fármaco.

Claims

REIVINDICAÇÕES
1. COMPLEXO MOLECULAR ANTINEOPLASICO-TESTOSTERONA composto por uma cadeia molecular de testosterona, um fármaco antineoplásico e uma ponte molecular caracterizado por ser baseado na dita cadeia molecular de testosterona unida quimicamente ao fármaco por meio de uma ponte molecular.
2. COMPLEXO MOLECULAR ANTINEOPLASICO-TESTOSTERONA conforme reivindicação 1 , caracterizado pelo fato de que o fármaco antineoplásico ser um fármaco comercial, como a daunorrubicina ou doxorrubicina (2), cisplatina (3), carboplatina (4) ou cisplatina-berenil (5).
3. COMPLEXO MOLECULAR ANTINEOPLASICO-TESTOSTERONA conforme reivindicação 1 , caracterizado pelo fato de que a ponte molecular é o carbamato (6).
4. COMPLEXO MOLECULAR ANTINEOPLASICO-TESTOSTERONA composto por uma cadeia molecular de testosterona, um fármaco antineoplásico e uma ponte molecular caracterizado por ser baseado na dita cadeia molecular de testosterona unida quimicamente ao fármaco por meio de uma molécula.
5. COMPLEXO MOLECULAR ANTINEOPLASICO-TESTOSTERONA conforme reivindicação 4, caracterizado pelo fato de que o fármaco antineoplásico ser um fármaco comercial, como a daunorrubicina ou doxorrubicina (2), cisplatina (3), carboplatina (4) ou cisplatina-berenil (5).
6. COMPLEXO MOLECULAR ANTINEOPLASICO-TESTOSTERONA conforme reivindicação 4, caracterizado pelo fato de que a molécula é uma molécula de Ν',Ν- disuccnimidil-carbonato (7).
PCT/BR2010/000161 2009-03-27 2010-03-26 Complexo molecular antineoplásico-testosterona Ceased WO2010108251A2 (pt)

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BRPI0901157-9A BRPI0901157A2 (pt) 2009-03-27 2009-03-27 complexo molecular antineoplásico-testosterona
BRPI0901157-9 2009-03-27

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011123911A1 (pt) * 2010-04-09 2011-10-13 Universidade Federal De Pernambuco - Ufpe Compostos antitumorais testosterona-quimioterápico
WO2012142687A1 (pt) * 2011-04-19 2012-10-26 5, deemedUNIVERSIDADE FEDERAL DE PERNAMBUCO - UFPE Composto antitumoral testosterona-(iodo radioativo)
US11826430B2 (en) 2019-05-14 2023-11-28 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
US11834458B2 (en) 2021-03-23 2023-12-05 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
US11952349B2 (en) 2019-11-13 2024-04-09 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
US12006314B2 (en) 2021-05-03 2024-06-11 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
US12398121B2 (en) 2018-05-14 2025-08-26 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BRMU8701986U2 (pt) * 2007-09-28 2010-02-23 Gerson Silva Paiva complexo molecular antineoplásico-testosterona

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011123911A1 (pt) * 2010-04-09 2011-10-13 Universidade Federal De Pernambuco - Ufpe Compostos antitumorais testosterona-quimioterápico
WO2012142687A1 (pt) * 2011-04-19 2012-10-26 5, deemedUNIVERSIDADE FEDERAL DE PERNAMBUCO - UFPE Composto antitumoral testosterona-(iodo radioativo)
US12398121B2 (en) 2018-05-14 2025-08-26 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
US11826430B2 (en) 2019-05-14 2023-11-28 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
US12208141B2 (en) 2019-05-14 2025-01-28 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
US11952349B2 (en) 2019-11-13 2024-04-09 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
US11834458B2 (en) 2021-03-23 2023-12-05 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
US12006314B2 (en) 2021-05-03 2024-06-11 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds

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BRPI0901157A2 (pt) 2010-11-16
WO2010108251A3 (pt) 2010-12-02

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