CA2155329A1 - Acylfulvene analogues as antitumor agents - Google Patents

Acylfulvene analogues as antitumor agents

Info

Publication number
CA2155329A1
CA2155329A1 CA002155329A CA2155329A CA2155329A1 CA 2155329 A1 CA2155329 A1 CA 2155329A1 CA 002155329 A CA002155329 A CA 002155329A CA 2155329 A CA2155329 A CA 2155329A CA 2155329 A1 CA2155329 A1 CA 2155329A1
Authority
CA
Canada
Prior art keywords
acylfulvene
analogues
antitumor agents
subject
cell growth
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CA002155329A
Other languages
French (fr)
Other versions
CA2155329C (en
Inventor
Michael J. Kelner
Trevor C. Mcmorris
Raymond Taetle
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of California
Original Assignee
Michael J. Kelner
Trevor C. Mcmorris
Raymond Taetle
The Regents Of The University Of California
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 Michael J. Kelner, Trevor C. Mcmorris, Raymond Taetle, The Regents Of The University Of California filed Critical Michael J. Kelner
Publication of CA2155329A1 publication Critical patent/CA2155329A1/en
Application granted granted Critical
Publication of CA2155329C publication Critical patent/CA2155329C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • 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
    • A61K31/12—Ketones
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • 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
    • A61P35/02—Antineoplastic agents specific for leukemia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C07C45/46—Friedel-Crafts reactions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/657—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings
    • C07C49/665—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings a keto group being part of a condensed ring system
    • C07C49/67—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings a keto group being part of a condensed ring system having two rings, e.g. tetralones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/657—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings
    • C07C49/683—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings having unsaturation outside the aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
    • C07C49/723—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups polycyclic
    • C07C49/727—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups polycyclic a keto group being part of a condensed ring system
    • C07C49/737—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups polycyclic a keto group being part of a condensed ring system having three rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
    • C07C49/747—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
    • C07C49/755—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups a keto group being part of a condensed ring system with two or three rings, at least one ring being a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/007—Esters of unsaturated alcohols having the esterified hydroxy group bound to an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/93—Spiro compounds
    • C07C2603/94—Spiro compounds containing "free" spiro atoms

Abstract

A method of inhibiting tumor cell growth in a subject is provided comprising contacting the tumor with a therapeutic amount of an acylfulvene analog having structure (I), wherein die analog is capable of inhibiting tumor cell growth without excessive toxicity to the subject and wherein R is (a), where R1= alkyl, aryl, NH2, NHR, or NR2.
CA002155329A 1993-02-09 1994-02-02 Acylfulvene analogues as antitumor agents Expired - Fee Related CA2155329C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/015,179 US5439936A (en) 1989-10-03 1993-02-09 Method of treating certain tumors using illudin analogs
US08/015,179 1993-02-09
PCT/US1994/001232 WO1994018151A1 (en) 1993-02-09 1994-02-02 Acylfulvene analogues as antitumor agents

Publications (2)

Publication Number Publication Date
CA2155329A1 true CA2155329A1 (en) 1994-08-18
CA2155329C CA2155329C (en) 2006-08-15

Family

ID=21769946

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002155329A Expired - Fee Related CA2155329C (en) 1993-02-09 1994-02-02 Acylfulvene analogues as antitumor agents

Country Status (22)

Country Link
US (3) US5439936A (en)
EP (1) EP0683762B1 (en)
JP (1) JP3908270B2 (en)
KR (1) KR100311327B1 (en)
CN (1) CN1046934C (en)
AT (1) ATE174894T1 (en)
AU (1) AU676889B2 (en)
BR (1) BR9405689A (en)
CA (1) CA2155329C (en)
CZ (1) CZ288596B6 (en)
DE (1) DE69415507T2 (en)
DK (1) DK0683762T3 (en)
ES (1) ES2125441T3 (en)
GR (1) GR3029736T3 (en)
HU (1) HU220059B (en)
MD (1) MD1418G2 (en)
NO (1) NO318648B1 (en)
NZ (1) NZ262282A (en)
PL (1) PL175024B1 (en)
RU (1) RU2145849C1 (en)
TJ (1) TJ266B (en)
WO (1) WO1994018151A1 (en)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5932553A (en) 1996-07-18 1999-08-03 The Regents Of The University Of California Illudin analogs useful as antitumor agents
US5723632A (en) * 1996-08-08 1998-03-03 Mgi Pharma, Inc. Total synthesis of antitumor acylfulvenes
US7141603B2 (en) * 1999-02-19 2006-11-28 The Regents Of The University California Antitumor agents
US6025328A (en) * 1998-02-20 2000-02-15 The Regents Of The University Of California Antitumor agents
US6436916B1 (en) 2000-10-12 2002-08-20 Alvin Guttag Ibuprofen-aspirin and hydroxymethylacylfulvene analogs
US7015247B2 (en) * 2000-10-12 2006-03-21 Alvin Guttag Ibuprofen-aspirin, hydroxymethylacylfulvene analogs and L-sugar illudin analogs
CA2571421A1 (en) 2004-06-24 2006-01-05 Nicholas Valiante Compounds for immunopotentiation
US7655695B2 (en) * 2005-08-03 2010-02-02 The Regents Of The University Of California Illudin analogs useful as anticancer agents
TWI522109B (en) * 2009-01-26 2016-02-21 臺北醫學大學 Use of pterosin compounds for treating diabetes and obesity
US10285955B2 (en) 2014-04-10 2019-05-14 Af Chemicals, Llc Affinity medicant conjugate
US11135182B2 (en) 2014-04-10 2021-10-05 Af Chemicals, Llc Affinity medicant conjugates
JP2017518359A (en) 2014-04-10 2017-07-06 エイエフ ケミカルス, エルエルシーAf Chemicals, Llc Affinity drug conjugate
CN106083953A (en) * 2016-06-15 2016-11-09 成都医学院 A kind of from fiddlehead, extract former pteroside and the method preparing high purity raw pteroside
US20210137850A1 (en) * 2017-03-15 2021-05-13 Memorial Sloan Kettering Cancer Center Diagnosis & treatment of ercc3-mutant cancer
KR20210087435A (en) * 2018-09-04 2021-07-12 랜턴 파마 인코포레이티드 Iludin analogs, uses thereof, and methods for their synthesis
EP3667323A1 (en) 2018-12-11 2020-06-17 Kelner, Michael Methods, compositions and devices for treating cancer with illudofulvenes
RU2738848C1 (en) * 2019-10-24 2020-12-17 Общество с ограниченной ответственностью "Научно-исследовательский институт ХимРар" (ООО "НИИ ХимРар") Hepatitis b virus (hbv) inhibitor, which is a derivative of n-{3-[6-(dialkylamino)pyridazine-3-yl]phenyl}aryl sulphonamide derivatives and derivatives of n-{4-[6-(dialkylamino)pyridazine-3-yl]phenyl}aryl sulphonamide
US11591295B2 (en) 2019-11-25 2023-02-28 Af Chemicals Llc Affinity illudofulvene conjugates
EP4035684A1 (en) 2019-11-25 2022-08-03 AF Chemical LLC Affinity illudofulvene conjugates
CN112972443A (en) * 2021-03-29 2021-06-18 杭州添帆生物科技有限公司 Anticancer medicine and its application
WO2023239821A2 (en) * 2022-06-07 2023-12-14 Lantern Pharma Inc. Treating cancers with combinations of acylfulvenes with ibrutinib or bortezomib
WO2024016014A2 (en) * 2022-07-15 2024-01-18 Lantern Pharma Inc. Method for treating breast cancers and parp resistant breast cancers

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69028320T2 (en) * 1989-10-03 1997-03-06 Univ California ILLUDINE ANALOG, USED AS AN ANTI-TUMOR MEDICINE
GB9017024D0 (en) * 1990-08-03 1990-09-19 Erba Carlo Spa New linker for bioactive agents
FI85318C (en) * 1990-08-14 1992-03-25 Tecnomen Oy COMPENSATION AV FELET I EN KLOCKAS GAONG.
JPH06223404A (en) * 1993-01-25 1994-08-12 Mitsubishi Kasei Corp Optical information recording medium

Also Published As

Publication number Publication date
CN1119854A (en) 1996-04-03
AU676889B2 (en) 1997-03-27
DK0683762T3 (en) 1999-08-23
CN1046934C (en) 1999-12-01
RU2145849C1 (en) 2000-02-27
KR100311327B1 (en) 2001-12-28
NO953099L (en) 1995-10-09
AU6170094A (en) 1994-08-29
ATE174894T1 (en) 1999-01-15
CA2155329C (en) 2006-08-15
EP0683762A1 (en) 1995-11-29
HUT72450A (en) 1996-04-29
MD1418G2 (en) 2000-10-31
ES2125441T3 (en) 1999-03-01
DE69415507D1 (en) 1999-02-04
NO318648B1 (en) 2005-04-25
BR9405689A (en) 1995-11-21
NZ262282A (en) 1997-06-24
CZ198695A3 (en) 1996-01-17
EP0683762B1 (en) 1998-12-23
HU9502358D0 (en) 1995-10-30
US5563176A (en) 1996-10-08
WO1994018151A1 (en) 1994-08-18
PL310159A1 (en) 1995-11-27
JPH08506812A (en) 1996-07-23
DE69415507T2 (en) 1999-08-12
MD960212A (en) 1999-01-31
TJ266B (en) 2000-08-07
US5523490A (en) 1996-06-04
HU220059B (en) 2001-10-28
JP3908270B2 (en) 2007-04-25
CZ288596B6 (en) 2001-07-11
US5439936A (en) 1995-08-08
GR3029736T3 (en) 1999-06-30
MD1418F2 (en) 2000-02-29
PL175024B1 (en) 1998-10-30
NO953099D0 (en) 1995-08-07

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