WO2000077027A3 - Serine protease inhibitors - Google Patents

Serine protease inhibitors Download PDF

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Publication number
WO2000077027A3
WO2000077027A3 PCT/GB2000/002291 GB0002291W WO0077027A3 WO 2000077027 A3 WO2000077027 A3 WO 2000077027A3 GB 0002291 W GB0002291 W GB 0002291W WO 0077027 A3 WO0077027 A3 WO 0077027A3
Authority
WO
WIPO (PCT)
Prior art keywords
serine protease
protease inhibitors
tryptase
compounds
formula
Prior art date
Application number
PCT/GB2000/002291
Other languages
French (fr)
Other versions
WO2000077027A2 (en
Inventor
John Walter Liebeschuetz
Stephen Clinton Young
Sarah Elizabeth Lively
Martin James Harrison
Bohdan Waszkowycz
Phillip John Morgan
Original Assignee
Protherics Molecular Design Lt
John Walter Liebeschuetz
Stephen Clinton Young
Sarah Elizabeth Lively
Martin James Harrison
Bohdan Waszkowycz
Phillip John Morgan
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
Priority claimed from GBGB9913823.2A external-priority patent/GB9913823D0/en
Priority claimed from GBGB9918741.1A external-priority patent/GB9918741D0/en
Priority claimed from GBGB9929553.7A external-priority patent/GB9929553D0/en
Priority claimed from GBGB9929552.9A external-priority patent/GB9929552D0/en
Priority to AU55460/00A priority Critical patent/AU5546000A/en
Application filed by Protherics Molecular Design Lt, John Walter Liebeschuetz, Stephen Clinton Young, Sarah Elizabeth Lively, Martin James Harrison, Bohdan Waszkowycz, Phillip John Morgan filed Critical Protherics Molecular Design Lt
Priority to ES00981478T priority patent/ES2282152T3/en
Priority to AT00981478T priority patent/ATE355284T1/en
Priority to DE60033689T priority patent/DE60033689T2/en
Priority to US10/148,174 priority patent/US6916957B2/en
Priority to EP00981478A priority patent/EP1240154B1/en
Priority to CA2394276A priority patent/CA2394276C/en
Priority to PCT/GB2000/004764 priority patent/WO2001044226A1/en
Priority to AU18713/01A priority patent/AU1871301A/en
Publication of WO2000077027A2 publication Critical patent/WO2000077027A2/en
Publication of WO2000077027A3 publication Critical patent/WO2000077027A3/en
Priority to PCT/GB2001/002566 priority patent/WO2001096305A1/en
Priority to DE60124397T priority patent/DE60124397T2/en
Priority to CA2413061A priority patent/CA2413061C/en
Priority to AU6407701A priority patent/AU6407701A/en
Priority to JP2002510448A priority patent/JP2004503538A/en
Priority to AT01938399T priority patent/ATE344795T1/en
Priority to ES01938399T priority patent/ES2275683T3/en
Priority to AU2001264077A priority patent/AU2001264077B2/en
Priority to US10/296,245 priority patent/US7074934B2/en
Priority to EP01938399A priority patent/EP1294691B1/en
Priority to US09/988,082 priority patent/US6740682B2/en
Priority to US10/752,568 priority patent/US7220781B2/en
Priority to US11/126,309 priority patent/US7157585B2/en
Priority to US11/186,870 priority patent/US7381734B2/en
Priority to US11/712,906 priority patent/US7928137B2/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/36—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
    • C07C255/60—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton at least one of the singly-bound nitrogen atoms being acylated
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    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
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    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
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    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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    • C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
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Abstract

Compounds of formula (I) where R2, each X, L, Y, Cy, Lp, D and n are as defined in the specification, are serine protease (especially tryptase) inhibitors useful as antiinflammatory agents.
PCT/GB2000/002291 1997-08-29 2000-06-13 Serine protease inhibitors WO2000077027A2 (en)

Priority Applications (24)

Application Number Priority Date Filing Date Title
AU55460/00A AU5546000A (en) 1999-06-14 2000-06-13 Compounds
AU18713/01A AU1871301A (en) 1999-12-14 2000-12-13 Serine protease inhibitors
PCT/GB2000/004764 WO2001044226A1 (en) 1999-12-14 2000-12-13 Serine protease inhibitors
ES00981478T ES2282152T3 (en) 1999-12-14 2000-12-13 SERINA PROTEASA INHIBITORS.
CA2394276A CA2394276C (en) 1999-12-14 2000-12-13 Serine protease inhibitors
EP00981478A EP1240154B1 (en) 1999-12-14 2000-12-13 Serine protease inhibitors
AT00981478T ATE355284T1 (en) 1999-12-14 2000-12-13 INHIBITORS OF SERINE PROTEASES
DE60033689T DE60033689T2 (en) 1999-12-14 2000-12-13 INHIBITORS OF SERIN PROTEASES
US10/148,174 US6916957B2 (en) 1999-12-14 2000-12-13 Serine protease inhibitors
AT01938399T ATE344795T1 (en) 2000-06-13 2001-06-12 INHIBITORS OF SERINE PROTEASES
ES01938399T ES2275683T3 (en) 2000-06-13 2001-06-12 INHIBITORS OF SERINO PROTEASA.
AU2001264077A AU2001264077B2 (en) 2000-06-13 2001-06-12 Serine protease inhibitors
US10/296,245 US7074934B2 (en) 2000-06-13 2001-06-12 Serine protease inhibitors
PCT/GB2001/002566 WO2001096305A1 (en) 2000-06-13 2001-06-12 Serine protease inhibitors
DE60124397T DE60124397T2 (en) 2000-06-13 2001-06-12 INHIBITORS OF SERIN PROTEASES
EP01938399A EP1294691B1 (en) 2000-06-13 2001-06-12 Serine protease inhibitors
JP2002510448A JP2004503538A (en) 2000-06-13 2001-06-12 Serine protease inhibitor
CA2413061A CA2413061C (en) 2000-06-13 2001-06-12 Serine protease inhibitors
AU6407701A AU6407701A (en) 2000-06-13 2001-06-12 Serine protease inhibitors
US09/988,082 US6740682B2 (en) 1997-08-29 2001-11-19 Meta-benzamidine derivatives as serine protease inhibitors
US10/752,568 US7220781B2 (en) 1997-08-29 2004-01-08 Meta-benzamidine derivatives as serine protease inhibitors
US11/126,309 US7157585B2 (en) 1999-12-14 2005-05-11 Serine protease inhibitors
US11/186,870 US7381734B2 (en) 2000-06-13 2005-07-22 Serine protease inhibitors
US11/712,906 US7928137B2 (en) 1997-08-29 2007-03-02 Meta-benzamidine derivatives as serine protease inhibitors

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
GB9913823.2 1999-06-14
GBGB9913823.2A GB9913823D0 (en) 1999-06-14 1999-06-14 Compounds
US14206499P 1999-07-02 1999-07-02
US60/142,064 1999-07-02
GB9918741.1 1999-08-09
GBGB9918741.1A GB9918741D0 (en) 1999-08-09 1999-08-09 Compounds
GB9929552.9 1999-12-14
GB9929553.7 1999-12-14
GBGB9929552.9A GB9929552D0 (en) 1999-12-14 1999-12-14 Compounds
GBGB9929553.7A GB9929553D0 (en) 1999-12-14 1999-12-14 Compounds

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
PCT/GB1998/002605 Continuation-In-Part WO1999011658A1 (en) 1997-08-29 1998-08-28 Meta-benzamidine derivatives as serin protease inhibitors
US48567800A Continuation-In-Part 1997-08-29 2000-02-25

Related Child Applications (3)

Application Number Title Priority Date Filing Date
PCT/GB1998/002605 Continuation-In-Part WO1999011658A1 (en) 1997-08-29 1998-08-28 Meta-benzamidine derivatives as serin protease inhibitors
US09485678 Continuation-In-Part 2000-02-25
US09/988,082 Continuation-In-Part US6740682B2 (en) 1997-08-29 2001-11-19 Meta-benzamidine derivatives as serine protease inhibitors

Publications (2)

Publication Number Publication Date
WO2000077027A2 WO2000077027A2 (en) 2000-12-21
WO2000077027A3 true WO2000077027A3 (en) 2001-05-25

Family

ID=56290032

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/GB2000/002296 WO2000076970A2 (en) 1999-06-14 2000-06-13 Serine protease inhibitors
PCT/GB2000/002291 WO2000077027A2 (en) 1997-08-29 2000-06-13 Serine protease inhibitors

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/GB2000/002296 WO2000076970A2 (en) 1999-06-14 2000-06-13 Serine protease inhibitors

Country Status (4)

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EP (1) EP1192135A2 (en)
AU (2) AU5546000A (en)
CA (1) CA2383008A1 (en)
WO (2) WO2000076970A2 (en)

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