WO2000069833A1 - Anticoagulants a base d'uracils d'aryle polycycliques et d'heteroaryles - Google Patents

Anticoagulants a base d'uracils d'aryle polycycliques et d'heteroaryles Download PDF

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Publication number
WO2000069833A1
WO2000069833A1 PCT/US2000/008226 US0008226W WO0069833A1 WO 2000069833 A1 WO2000069833 A1 WO 2000069833A1 US 0008226 W US0008226 W US 0008226W WO 0069833 A1 WO0069833 A1 WO 0069833A1
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group
carbon
hydrido
amino
hydroxy
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PCT/US2000/008226
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English (en)
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Michael S. South
Darin E. Jones
Melvin L. Rueppel
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Pharmacia Corporation
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Priority to CA002373610A priority Critical patent/CA2373610A1/fr
Priority to MXPA01011806A priority patent/MXPA01011806A/es
Priority to BR0011273-9A priority patent/BR0011273A/pt
Priority to EP00931917A priority patent/EP1178971A1/fr
Priority to AU49724/00A priority patent/AU771740B2/en
Priority to NZ514877A priority patent/NZ514877A/en
Priority to US09/979,542 priority patent/US6716838B1/en
Priority to JP2000618250A priority patent/JP2002544263A/ja
Priority to KR1020017014750A priority patent/KR20010113969A/ko
Publication of WO2000069833A1 publication Critical patent/WO2000069833A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/06—1,2,4-Triazines
    • C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
    • C07D253/07—1,2,4-Triazines having three 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
    • C07D253/075—Two hetero atoms, in positions 3 and 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • This invention is in the field of anticoagulant therapy, and specifically relates to compounds, compositions and methods for preventing and treating thrombotic conditions such as coronary artery and cerebrovascular disease. More particularly, the invention relates to substituted polycyclic aryl and heteroaryl uracil compounds that inhibit serine proteases of the coagulation 10 cascade.
  • Physiological systems control the fluidity of blood in mammals [Majerus, P. W. et al: Anticoagulant, Thrombolytic, and Antiplplatelet Drugs.
  • platelets first adhere to macromolecules in subendothelian regions of an injured and/or damaged vessels. These platelets aggregate to form the primary hemostatic plug and stimulate local activation of plasma coagulation factors leading to generation of a fibrin clot that reinforces the aggregated platelets.
  • Plasma coagulation factors include factors II, V, VII, VIII, IX, X, XI,
  • protease zymogens 25 and XII; these are also called protease zymogens. These coagulation factors or protease zymogens are activated by serine proteases leading to coagulation in a so called “coagulation cascade” or chain reaction [Handin, R. I.: Bleeding and Thrombosis. In Wilson, J., et al. editors: Harrison's Principles of Internal Medicine. 12th Edition, New York, McGraw-Hill Book Co., 1991,p.350].
  • Coagulation or clotting occurs in two ways through different pathways.
  • An intrinsic or contact pathway leads from XII to Xiia to XIa to IXa and to the conversion of X to Xa.
  • Xa with factor Va converts prothrombin (II) to thrombin (Ha) leading to conversion of fibrinogen to fibrin.
  • Polymerization of fibrin leads to a fibrin clot.
  • An extrinsic pathway is initiated by the conversion
  • coagulation factor VII 35 of coagulation factor VII to Vila by Xa.
  • Tissue Factor and Vila accelerates formation of Xa in the presence of calcium ion and phospholipids. Formation of Xa leads to thrombin, fibrin, and a fibrin clot as described above.
  • the presence of one or more of these many different coagulation factors and two distinct pathways of clotting could enable the efficacious, selective control and better understanding of parts of the coagulation or clotting process.
  • thrombosis results when platelet aggregation and/or a fibrin clot blocks (i.e., occludes) a blood vessel.
  • Arterial thrombosis may result in ischemic necrosis of the tissue supplied by the artery.
  • a myocardial infarction or heart attack can result.
  • a thrombosis occurring in a vein may cause tissues drained by the vein to become edematous and inflamed.
  • Thrombosis of a deep vein may be complicated by a pulmonary embolism.
  • Preventing or treating clots in a blood vessel may be therapeutically useful by inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, inhibiting embolus formation, and for treating or preventing unstable angina, refractory angina, myocardial infarction, transient ischemic attacks, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, ocular build up of fibrin, and reocclusion or restenosis of recanalized vessels.
  • the present invention relates to a class of compounds comprising Substituted Polycyclic Aryl and Heteroaryl uracils, which are beneficial in anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular disease, as given in Formula (I):
  • J and J are independently selected from the group consisting of O and S;
  • J is optionally selected from the group consisting of CH-R and N-R
  • R is a linear spacer moiety having from 1 through 4 contiguous atoms linked to the point of bonding of a substituent selected from the group
  • J is optionally selected from the group consisting of CH-R and N-R
  • R is a linear spacer moiety having from 1 through 4 contiguous atoms linked to the point of bonding of a substituent selected from the group
  • 4a 4b 14 15 consisting of R t , R , R , R and R to form a heterocyclyl ring having 5 through 8 contiguous members; a b J and J are optionally independently selected from the group
  • J is optionally selected from the group consisting of CH-R and N-R
  • R is a linear spacer moiety having from 1 through 4 contiguous atoms 39 40 linked to the points of bonding of both R and R to form a heterocyclyl ring having 5 through 8 contiguous members;
  • D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one can be a cov s
  • K must be a covalent bond when two of D , D , J , J and K are O and S,
  • R , R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkyl sulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulf
  • R , R , R , R , R , R , and R are independently optionally h 16 19 h Q with the proviso that no more than one of R and R is Q at the same
  • T R, 3 and _, R r, 33 , ⁇ R> 33 and , R T, , R. 3 and J r R, 35 , and , T R, 5 and , R, 3 6 are independently optionally selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group
  • J T R, 6 are used , at th -.e same time;
  • R and R , R and R , R and R , and R and R are independently optionally selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group consisting of spacer pairs R and R , R and R , R and R , and R
  • 3 4 3 4 consisting of C, N, O, and S, no more than one of D , D , J , and J is O, no
  • R , R , R , and R are N with the proviso that R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • B is optionally selected from the group consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkylenyl, C3-C8 alkynyl, C2-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of R32, R33,
  • B is optionally selected from the group consisting of C3-C15 cycloalkyl, C5-C10 cycloalkenyl, C4-C12 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon is optionally
  • a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbons and nitrogen adjacent to the carbon atom at the point of attachment are optionally
  • R 33 optionally substituted with R , and a ring carbon or nitrogen four atoms from
  • A is selected from the group consisting of single covalent bond
  • W is selected from the group consisting of O, S, C(O), C(S), C(O)S, C(S)O, C(O)N(R 7 ), C(S)N(R ? ), (R ? )NC(O), (R ? )NC(S), S(O), S(O) 2 ,
  • R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, alkenyl, aryl, aralkyl, aryloxy, alkoxy, alkenyloxy, alkylthio, alkylamino, arylthio, arylamino, acyl, aroyl, heteroaroyl, aralkoxyalkyl, heteroaralkoxyalkyl, , aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulf onylalkyl, heteroaryl, heteroaryl oxy, heteroarylamino, heteroaralkyl, heteroaralkylamino, and heteroaryloxyalkyl;
  • J J . R , R , R , R , R , R and R are independently selected from the group consisting of amidino, hydroxyamino, hydrido, hydroxy, halo, cyano, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, aminoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkylsulfinylalkyl, alkylsulf onylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl,
  • halocycloalkoxy halocycloalkoxy alkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, di carboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfmyl, alkylsulf onyl, haloalkylsulfinyl.
  • haloalkylsulfonyl arylsulfinyl, arylsulfinylalkyl, arylsulf onyl, arylsulf onylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulf onylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, trialkyls
  • R and R when bonded to different carbons, are optionally taken together to form a group selected from the group consisting of covalent bond, alkylene, haloalkylene, and a linear moiety spacer selected to form a ring selected from the group consisting of cycloalkyl ring having from 5 through 8 contiguous members, cycloalkenyl ring having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;
  • R and R when bonded to different carbons, are optionally taken together to form a group selected from the group consisting of covalent bond, alkylene, haloalkylene, and a linear moiety spacer selected to form a ring selected from the group consisting of a cycloalkyl ring having from 5 through 8 contiguous members, a cycloalkenyl ring having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;
  • R and R when bonded to different carbons, are optionally taken together to form a group selected from the group consisting of covalent bond, alkylene, haloalkylene, and a linear moiety spacer selected to form a ring selected from the group consisting of cycloalkyl ring having from 5 through 8 contiguous members, cycloalkenyl ring having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members; 5 ⁇ is selected from the group consisting of NR , O, C(O), C(S), S,
  • R is selected from the group consisting of hydrido, hydroxy, amino, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxy, aralkoxy, alkoxy, alkenyloxy, alkylthio, arylthio, aralkoxyalkyl, heteroaralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulf onylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,
  • N alkylene, haloalkylene, and a linear moiety spacer having from 2 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;
  • M is selected from the group consisting of N and R -C;
  • R 2 and R 1 are independently selected from the group consisting of Z 0 -
  • R is optionally selected from the group consisting of amino, aminoalkyl, alkylamino, amidino, guanidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, alkylthio, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, nitro, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, and phosphono; 2 R is optionally selected from the group consisting of amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfonium;
  • R 2 and R 4a , R 2 and R 4b , R 2 and R 14 , and R 2 and R 15 are optionally independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 2 through 5 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having from 5 through 8 contiguous members with the
  • R , R and R , R and R , and R and R is used at the same time;
  • R is optionally independently selected to form a linear moiety having
  • Z is selected from the group consisting of covalent single bond
  • CR R C; vinylidene), ethynylidene (C ⁇ C; 1,2-ethynyl), 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3- cyclopentyl, 2,3-morpholinyl, 2,4-mo holinyl, 2,6-mo ⁇ holinyl, 3,4- morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 2,3- piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 13-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3- pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-piperid
  • R and R are independently selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, acyl, aroyl, aralkanoyl, heteroaroyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulf onylalkyl, aralkyl thioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halo
  • R and R are optionally taken together to form a linear moiety spacer having from 2 through 7 contiguous atoms and forming a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;
  • Q is formula (II):
  • D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more
  • 1 2 1 2 1 1 can be O, no more than one of D , D , J , J and K can be S, one of D ,
  • D , J , J and K must be a covalent bond when two of D , D , J , J and
  • 1 1 2 1 2 1 K are O and S, and no more than four of D , D , J , J and K can be N,
  • R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • Q is optionally selected from formula (III):
  • 3 4 3 4 consisting of C, N, O, and S, no more than one of D , D , J , and J is O, no
  • R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • Q is optionally selected from the group consisting of hydrido, alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl, partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy alkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkyl with the proviso that Z is selected from other than a single covalent bond when Q is hydrido;
  • 4a 4b K is (CR R ) n wherein n is an integer selected from 1 through 4;
  • R and R are independently selected from the group consisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl, aryl, aralkyl, aralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, aralkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkenyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl, alkylsulfinylalkyl, alkylsulf onylalkyl, haloalkylsulfinyl, arylsulf ⁇ nylalkyl, arylsulfon
  • 4a 4b R and R when bonded to the same carbon, are optionally taken together to form a group selected from the group consisting of oxo, thiono, and a linear spacer moiety having from 2 through 7 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkyl ring having 3 through 8 contiguous members, a cycloalkenyl ring having 5 through 8 contiguous members, and a heterocyclyl ring having 5 through 8 contiguous
  • E is E , when K is (CR R ) ⁇ , wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R ? ), (R 7 )NC(O), C(S)N(R ? ), (R 7 )NC(S),
  • K is optionally selected to be (CH(R )):-T wherein j is selected from a integer from 0 through 3 and T is selected from the group consisting of single
  • E is optionally E , when K is (CH(R )) -T, wherein E is selected from the group consisting of a covalent single bond, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R 7 ), (R 7 )NC(O), C(S)N(R 7 ), (R ? )NC(S),
  • K is optionally selected to be G-(CH(R )) j ⁇ wherein k is selected from an integer from 1 through 3 and G is selected from the group consisting of O,
  • R is other than hydroxy, cyano, halo, amino, alkylamino, dialkylamino, and sulfhydryl when k is 1;
  • E is optionally E when K is G-(CH(R )) ⁇ wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S),
  • Y° is formula (IV):
  • K is independently selected from the group
  • R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • R and R are independently optionally taken together to form a linear moiety spacer having from 3 through 6 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members, a partially saturated heterocyclyl ring having from 5 through 8 contiguous members, a heteroaryl having from 5 through 6 contiguous members, and an aryl;
  • R and R are independently optionally taken together to form a linear moiety spacer having from 3 through 6 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members, a partially saturated heterocyclyl ring having from 5 through 8 contiguous members, a heteroaryl having from 5 through 6 contiguous members, and an aryl;
  • b 20 21 Q is selected from the group consisting of NR R ,
  • R , and R are independently selected from the group consisting of hydrido, amino, alkyl, hydroxy, alkoxy, aminoalkylenyl, alkylamino, dialkylamino, and
  • R , R , and R must be other than be hydroxy, alkoxy, alkylamino,
  • R and R , R and R , and R and R are independently optionally selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 4 through 7 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having 5 through 8 contiguous members with the proviso that no more than
  • Q is optionally selected from the group consisting of
  • R , R , and R can be hydroxy, alkoxy, alkyleneamino, alkylamino, 23 24 amino, or dialkylamino when two of the group consisting of R , R , and
  • Q is optionally selected from the group consisting of
  • R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylenylamino, amino, alkylamino, dialkylamino, and hydroxyalkyl;
  • R and R are optionally taken together to form a linear spacer moiety having from 4 through 7 contiguous atoms connecting the points of bonding to form a heterocyclyl ring having 5 through 8 contiguous members;
  • R 30 (O)POP(O)R 3 °, Si(R 29 )R 28 , Si(R 29 )R 28 Si(R 29 )R 28 ,
  • P(S)R C(R ) C(R ), DC(R )(R )D, OP(OR )R , P(O)R , P(S)R ,
  • J H is independently selected from the group consisting of OR , SR and
  • 27 R is selected from the group consisting of hydrido, alkyl, alkenyl, alkynyl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulf onylalkyl, aralkyl thioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, halocycloalkyl, halocycloalkenyl
  • R and R are independently selected from the group consisting of hydrido, hydroxy, thiol, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, heteroaryloxyalkyl, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulf onylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenyl, cyclo
  • R and R are optionally taken to form a linear moiety spacer group having from 2 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;
  • 26 R are independently optionally selected to form a spacer pair wherein a spacer pair is taken together from the points of bonding of selected spacer pair members to form the group L-U-V wherein L, U, and V are independently selected from the group of 1,2-disubstituted radicals consisting of a cycloalkyl radical, a cycloalkenyl radical wherein cycloalkyl and cycloalkenyl radicals are substituted with one or
  • 26 R are independently optionally selected to form a spacer pair wherein a spacer pair is taken together from the points of bonding of selected spacer pair members to form the group L-U-V wherein L, U, and V are independently selected from the group of radicals consisting of 1,2-disubstituted alkylene radicals and 1,2- disubstituted alkenylene radical wherein said 1,2-substitutents are independently
  • s Q is selected from the group consisting of a single covalent bond
  • W is selected from 1 through 4, and W is selected from the group consisting of O,
  • CR R C; vinylidene), ethynylidene (C- ⁇ C; 1,2-ethynyl), 1,2-cyclopropyl,
  • R and R when bonded to different carbons, are optionally taken together to form a linear moiety spacer having from 1 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;
  • R and R when bonded to different carbons, are taken together to form a linear moiety spacer having from 1 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;
  • R and R when bonded to different carbons, are taken together to form a linear moiety spacer having from 1 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;
  • R and R when bonded to the same carbon, are taken together to form a group selected from a group consisting of oxo, thiono, alkylene, haloalkylene, and a linear moiety spacer having from 2 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;
  • Y is optionally Q -Q wherein Q is selected from the group
  • W is selected from the group consisting of W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R 14 ), (R 14 )NC(O), C(S)N(R 14 ), (R 14 )NC(S),
  • Y° is optionally Q b -Q SSS wherein Q SSS is (CHCR 38 )),.- ⁇ , r is an
  • W * ⁇ is selected from the group consisting of 1,1-cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2- cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3 -cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4- morpholinyl, 3,5-morpholinyl, 1,2- piperazinyl, 1,3-piperazinyl, 1,4- piperazinyl, 23-piperazinyl, 2,5-piperazinyl, 2,6- piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,5- piperidinyl, 2,6- piperazinyl
  • Y° is optionally Q b -Q SSSr wherein Q SSSr is (CH(R 38 )) r -W 4 r is an
  • W is selected from the group consisting of 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2- cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,5- morpholinyl, 2,6-morpholinyl, 3,4-mo holinyl, 3,5-morpholinyl, 1,2- piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 2,3- piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,
  • Y° is optionally Q b -Q SSSS wherein Q SSSS is (CH(R 38 )) r -W 5 , r is an
  • wW 5 ⁇ is selected from the group consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl,
  • Y° is optionally Q b -Q ssssr wherein Q SSSSr is (CH(R 38 )) r -W 6 r is an
  • W is selected from the group consisting of
  • 1,4-indenyl 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl, 3,5-benz
  • hydrido containing nitrogen member of the ring of the W other than the points of attachment is optionally substituted with one or more of the group consisting of R , R , R , and R , with the proviso that Q is bonded to
  • a b J and J are independently selected from the group consisting of O and S;
  • B is formula (V):
  • D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more
  • K must be a covalent bond when two of D , D , J , J and K are O and S,
  • R , R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfomumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfin
  • R , R , R , R , R , R , and R are independently optionally b 16 19 h
  • T R, 3 and , r R. 33 , T R ⁇ 33 and -, R , T R, and -. T R 3 5 , and ⁇ R >5 and ⁇ ⁇ R36 are independently optionally selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group
  • R and R , R and R , R and R , and R and R are independently optionally selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through
  • B is optionally selected from the group consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, C2-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of
  • B is optionally selected from the group consisting of C3-C15 cycloalkyl, C5-C10 cycloalkenyl, C4-C12 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon is optionally
  • a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon atom at the point of attachment are optionally
  • A is selected from the group consisting of single covalent bond
  • W is selected from the group consisting of O, S, C(O), C(S), C(O)S, C(S)O, C(O)N(R ? ), C(S)N(R 7 ), (R ? )NC(O), (R 7 )NC(S), S(O), S(O) 2 ,
  • R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, acyl, aroyl, heteroaroyl, and alkoxyalkyl;
  • R , R , R , and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl, alkoxy, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl; R and R can be independently selected from the group consisting of acyl, aroyl, and heteroaroyl with the proviso that acyl is selected from other than formyl;
  • ⁇ is selected from the group consisting of NR , O, C(O), C(S), S,
  • R is selected from the group consisting of hydrido, hydroxy, amino, alkyl, alkoxy, alkoxyalkyl, haloalkyl, acyl, aroyl, and heteroaroyl;
  • R and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl, acyl, aroyl, heteroaroyl, acylamido, alkoxy, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, alkyl sulfonyl, haloalkylsulfonyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;
  • M is selected from the group consisting of N and R -C;
  • R 2 and R 1 are independently selected from the group consisting of Z 0 - Q, hydrido, alkyl, alkenyl, and halo;
  • R is optionally selected from the group consisting of amino, aminoalkyl, alkylamino, amidino, guanidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, alkylthio, dialkylsulfonium, trialkylphosphonium, dialkylsulfomumalkyl, heteroarylamino, nitro, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, and phosphono;
  • Z is selected from the group consisting of covalent single bond
  • W (CH(R ))
  • CR R C; vinylidene), ethynylidene (C ⁇ C; 1,2-ethynyl), 1,2-cyclopropyl,
  • R and R are independently selected from the group consisting of amidino, hydroxyamino, hydrido, hydroxy, amino, halo, cyano, aryloxy, hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, alkoxy, alkyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkoxyalkyl, heteroaryloxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, haloalken
  • D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more
  • K must be a covalent bond when two of D , D , J , J and K are O and S,
  • R , R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • 3 4 3 4 consisting of C, N, O, and S, no more than one of D , D , J , and J is O, no 3 4 3 4 1 2 more than one of D , D , J , and J is S, and no more than three of D , D ,
  • R , R , and R are N with the proviso that R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • Q is optionally selected from the group consisting of hydrido, alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl, partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl , haloalkoxy, haloalkenyl , halocycloalkyl , halocycloalkenyl , haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkyl with the proviso that
  • 4a 4b K is (CR R ) n wherein n is an integer selected from 1 through 2;
  • R and R are independently selected from the group consisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl, alkoxyalkyl, aralkyl, heteroaralkyl, alkylthioalkyl, haloalkyl, haloalkenyl, and cyanoalkyl; o 1 4a 4b 1
  • E is E , when K is (CR R ) n , wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R ? ), (R ? )NC(O), C(S)N(R 7 ), (R 7 )NC(S),
  • 4a 4b ethynylidene (C- ⁇ C; 1,2-ethynyl), and C CR R ; 14 K is optionally (CH(R )):-T wherein j is selected from a integer from
  • T is selected from the group consisting of single covalent
  • K is optionally G-(CH(R )) j - wherein k is selected from an integer from 1 through 2 and G is selected from the group consisting of O, S, and
  • R is other than hydroxy, cyano, halo, amino, alkylamino, dialkylamino, and sulfhydryl when k is 1;
  • E is optionally E when K is G-(CH(R )) j ⁇ , wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S),
  • D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more
  • K is independently selected from the group
  • D , D , J , and J are N when K is carbon with the provisos that R , R ,
  • R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • R and R are optionally independently taken together to form a linear moiety spacer having from 3 through 6 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members, a partially saturated heterocyclyl ring having from 5 through 8 contiguous members, a heteroaryl having from 5 through 6 contiguous members, and an aryl; b 20 21
  • Q is selected from the group consisting of NR R ,
  • NR R R oxy, alkyl, aminoalkylenyl, alkylamino, dialkylamino, be be 20 dialkylsulfomumalkyl, acylamino and Q , wherein Q is hydrido and R ,
  • R , and R are independently selected from the group consisting of hydrido, amino, alkyl, hydroxy, alkoxy, aminoalkylenyl, alkylamino, dialkylamino, and
  • R , R , and R must be other than be hydroxy, alkoxy, alkylamino,
  • R and R , and R and R are independently optionally selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 4 through 7 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having 5 through 8 contiguous members with the proviso that no more than
  • R and R is used at the same time
  • Q is optionally selected from the group consisting of
  • R 23 24 26 of R , R , and R is hydroxy, alkoxy, alkylamino, amino, and
  • Q is optionally selected from the group consisting of
  • R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, aminoalkylenyl, alkylamino, dialkylamino, amino, and hydroxyalkyl;
  • R and R are optionally taken together to form a linear spacer moiety having from 4 through 7 contiguous atoms connecting the points of bonding to form a heterocyclyl ring having 5 through 8 contiguous members;
  • Q is selected from the group consisting of a single covalent bond
  • az is an integer selected from 0 through 1
  • b is an integer selected from 1 through 4
  • W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R 14 ),
  • W is selected from the group
  • W ⁇ is selected from the group
  • 1,2-ethynyl 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3- cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-mo ⁇ holinyl, 2,4- mo ⁇ holinyl, 2,6-mo ⁇ holinyl, 3,4-mo ⁇ holinyl, 3,5-mo ⁇ holinyl, 1,2- piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl, 3,4- piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4- pyrrolidinyl, 2,5-pyrrolidinyl, 3,4
  • R and R are selected from other than halo and cyano when
  • Y is optionally Q -Q wherein Q is selected from the group
  • W is selected from the group consisting of W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R 14 ), (R M )NC(O), C(S)N(R 14 ), (R 14 )NC(S),
  • e and h are integers independently selected from 0 through 2 and w 2
  • R 38 ) f , (CH(R 14 )) C , and (CH(R 14 )) e are bonded to E°;
  • Y° is optiionally Q b -Q SSS wherein Q SSS is (C ⁇ R 38 )),. ⁇ , r is an
  • W ⁇ ⁇ is selected from the group consisting of
  • Y° is optionally Q b -Q SSSr wherein Q SSSr is (CH(R 38 )) r -W 4 r is an
  • W is selected from the group consisting of
  • W is selected from the group consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzof uranyl, 2,5-benzof uranyl, 2,6-benzof uranyl, 2,7-benzofuranyl, 3, 4-benzof uranyl, 3, 5-benzof uranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl,
  • Y is optionally Q -Q wherein Q is (CH(R )) r -W , r is an
  • W is selected from the group consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzof uranyl, 2,5-benzof uranyl, 2,6-benzofuranyl, 2,7-benzof uranyl, 3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,
  • a b J and J are independently selected from the group consisting of O and S;
  • D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more
  • K must be a covalent bond when two of D , D , J , J and K are O and S,
  • R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfomumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulf onylalkyl, aralkylsulfmyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfiny
  • R , R , R , R , and R are independently optionally
  • B is optionally selected from the group consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, C2-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the point
  • B is optionally selected from the group consisting of C3-C12 cycloalkyl, C5-C10 cycloalkenyl, and C4-C9 saturated heterocyclyl, wherein
  • each ring carbon is optionally substituted with R
  • a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time
  • R 10 is optionally substituted with R , a ⁇ ng carbon or nitrogen adjacent to the
  • R 12 33 to the R position is optionally substituted with R , and a ring carbon or
  • R positions is optionally substituted with R ;
  • A is selected from the group consisting of single covalent bond
  • W 7 7 selected from 0 through 1
  • pa is an integer selected from 0 through 6
  • W 7 7 is selected from the group consisting of O, S, C(O), C(0)N(R ), C(S)N(R ),
  • R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, and alkoxyalkyl;
  • R , R , R , and R are independently selected from the group consisting of hydrido, hydroxy, halo, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, and haloalkoxyalkyl;
  • R and R can be independently selected from the group consisting of aroyl and heteroaroyl
  • ⁇ is selected from the group consisting of NR , C(O), and S(O) 2 ;
  • R is selected from the group consisting of hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio, amino, aminoalkyl, alkylamino, amidino, guanidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, alkylthio, and phosphono;
  • Z is selected from the group consisting of covalent single bond
  • h are integers independently selected from 0 through 2 and W ⁇ is selected
  • R and R are independently selected from the group consisting of amidino, hydroxyamino, hydrido, hydroxy, amino, and alkyl:
  • D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more
  • R , R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • 4a 4b K is (CR R ) n wherein n is an integer selected from 1 through 2;
  • D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one is a covalent bond, K is C, no more than one of D , D , J , and J
  • Q is selected from the group consisting of NR R ,
  • R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, aminoalkylenyl, dialkylamino, alkylamino, and
  • R 23 24 26 of R , R , and R is hydroxy, alkylamino, amino, or dialkylamino when
  • Q is selected from the group consisting of a single covalent bond
  • W is selected from the group
  • W ⁇ is selected from the group
  • R and R are selected from other than halo and cyano when
  • 14 is selected from the group consisting of O, S, C(O), C(O)N(R ), 14 15 14 14 15 14 14
  • W ⁇ is selected from the group consisting of
  • Y° is optionally Q b -Q SSS wherein Q SSS is (C ⁇ R 38 )) ⁇ , r i s an
  • W W ⁇ iss selected from the group consisting of 1,1-cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2- cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-mo ⁇ holinyl, 2,4-mo ⁇ holinyl, 2,5-mo ⁇ holinyl, 2,6-mo ⁇ holinyl, 3,4- mo ⁇ holinyl, 3,5-mo ⁇ holinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4- piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 2,3-piperidinyl,
  • Y° is optionally Q b -Q SSSr wherein Q SSSr is (CH(R 38 )) r -W 4 , r is an
  • W is selected from the group consisting of 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2- cyclopentyl, 1,3-cyclopentyl, 2,3-mo ⁇ holinyl, 2,4-mo ⁇ holinyl, 2,5- mo ⁇ holinyl, 2,6-mo ⁇ holinyl, 3,4-mo ⁇ holinyl, 3,5-mo ⁇ holinyl, 1,2- piperazinyl, 1,3 -piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl, 2,5- piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 2,3- piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-pipe
  • Y° is optionally Q b -Q SSSS wherein Q SSSS is (CH(R 38 )) r -W 5 , r i s an
  • W ⁇ ⁇ is selected from the group consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzof uranyl, 2,5-benzofuranyl, 2,6-benzof uranyl, 2,7- benzof uranyl, 3, 4-benzof uranyl, 3, 5-benzof uranyl, 3, 6- benzof uranyl, 3, 7- benzof uranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
  • W is selected from the group consisting of
  • 1,4-indenyl 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzof uranyl, 2,6-benzofuranyl, 2,7- benzof uranyl, 3, 4-benzof uranyl, 3, 5-benzof uranyl, 3,6-benzofuranyl, 3, 7- benzof uranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophen
  • D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more
  • K must be a covalent bond when two of D , D , J , J and K are O and S,
  • T R, 9 «R 10 , n RH , TR, 12 , R r, 13 , R T, 32 , TR. 33 , TR, 34 , ⁇ R , and , rR, 36 are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino, alkoxyamino, nitro, lower alkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl, alkylsulfonyl, alkylsulf onylalkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsul
  • R , R , R , R , R , and R are independently optionally
  • B is optionally selected from the group consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the point of
  • B is optionally selected from the group consisting of C3-C12 cycloalkyl and C4-C9 saturated heterocyclyl, wherein each ring carbon may be
  • a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon atom at the point of attachment
  • 9 13 may be optionally substituted with R or R , a ring carbon or nitrogen
  • R 10 13 optionally substituted with R , a ring carbon or nitrogen adjacent to the R position and two atoms from the point of attachment is optionally substituted
  • R 10 11 and adjacent to the R position is optionally substituted with R , a ring carbon or nitrogen three atoms from the point of attachment and adjacent to the
  • R position is optionally substituted with R , and a ring carbon or nitrogen
  • A is selected from the group consisting of single covalent bond
  • 7 7 is selected from the group consisting of O, S, C(O), (R )NC(O), (R )NC(S), 7 and N(R ) with the proviso that no more than one of the group consisting of rr and pa is 0 at the same time;
  • R is selected from the group consisting of hydrido, hydroxy, and alkyl
  • R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl;
  • ⁇ is selected from the group consisting of NH and NOH;
  • M is selected from the group consisting of N and R -C;
  • R is selected from the group consisting of hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;
  • R 2 is Z°-Q
  • Z is selected from the group consisting of covalent single bond
  • W ⁇ is selected from
  • CR CR , 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2- cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3- mo ⁇ holinyl, 2,4-mo ⁇ holinyl, 2,6-mo ⁇ holinyl, 3,4-mo ⁇ holinyl, 3,5- mo ⁇ holinyl, 1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl, 2,6- piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl, 3, 4- piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3- pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,
  • R and R are independently selected from the group consisting of amidino, hydroxyamino, hydrido, hydroxy, amino, and alkyl;
  • Q is selected from the group consisting of hydrido, with the proviso that Z is other than a covalent single bond, and the formula (II):
  • D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more
  • R , R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • 4a 4b K is (CR R ) n wherein n is an integer selected from 1 through 2;
  • R and R are independently selected from the group consisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl; E is E , when K is (CR II ) n , wherein E is selected from the
  • D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one is a covalent bond, K is C, no more than one of D , D , J , and J
  • R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • R 23 24 more than one of R and R is hydroxy, amino, alkylamino, or dialkylamino at the same time;
  • R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, aminoalkylenyl, amino, dialkylamino, alkylamino, and hydroxyalkyl; s Q is selected from the group consisting of a single covalent bond,
  • W is selected from 1 through 3 and W is selected from the group consisting of
  • R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;
  • R is optionally selected from the group consisting of aroyl and heteroaroyl; Y° is optionally Q b -Q SS wherein Q SS is (CH(R 14 )) e -W 2 -(CH(R 15 )) h ,
  • e and h are integers independently selected from 1 through 2 and w 2
  • Y is optionally selected from the group consisting of Q -Q and Q -
  • Q SSSS1* wherein Q SSSS is (CH R ⁇ -W 5 and Q SSSsr is (CH(R 38 )) r -W 6 , r is an
  • W and W are independently selected from the group consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7- indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5- indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5 ⁇ benzofuranyl, 2,6- benzofuranyl, 2,7-benzof uranyl, 3, 4-benzof uranyl, 3, 5-benzof uranyl, 3,6- benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothio ⁇ henyl, 3,4-benzothiophenyl, 3,5- benzothiophenyl, 3,6-
  • W is optionally substituted with one or more of the group consisting of
  • J and J are each O;
  • B is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment is optionally substituted
  • R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino, alkoxyamino, alkanoyl, haloalkanoyl, nitro, lower alkylamino, alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulf onamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, alkyl enyl amino, carb
  • B is optionally selected from the group consisting of C3-C12 cycloalkyl and C4-C9 saturated heterocyclyl, wherein each ring carbon is
  • a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon atom at the point of
  • R 10 13 optionally substituted with R , a ring carbon or nitrogen adjacent to the R position and two atoms from the point of attachment is optionally substituted
  • R 10 11 and adjacent to the R position is optionally substituted with R , a ring carbon or nitrogen three atoms from the point of attachment and adjacent to the
  • R position is optionally substituted with R , and a ring carbon or nitrogen
  • R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino, alkyl enedi oxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulf onyl, alkylsulf onamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxyalkyl, carboxy, carboxamido, and cyano;
  • A is selected from the group consisting of single covalent bond and
  • W is selected from the group
  • R is selected from the group consisting of hydrido, hydroxy and alkyl
  • R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; ⁇ is NH;
  • M is selected from the group consisting of N and R -C;
  • R is selected from the group consisting of hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;
  • R 2 is Z°-Q
  • Z is selected from the group consisting of covalent single bond and
  • W ⁇ is selected from the group consisting of
  • CR CR , 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3- cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-mo ⁇ holinyl, 2,4- mo ⁇ holinyl, 2,6-mo ⁇ holinyl, 3,4-mo ⁇ holinyl, 3,5-mo ⁇ holinyl, 1,2- piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 13-piperidinyl, 2,3-piperidinyl, 2,4- piperidinyl, 2,6-piperidinyl, 3,4- piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 23-pyrrolidinyl, 2,4- pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrol
  • R and R are independently selected from the group consisting of hydrido, hydroxy, and amino;
  • Q is selected from the group consisting of hydrido, with the proviso that Z is other than a covalent single bond, aryl, and heteroaryl, wherein a carbon adjacent to the carbon at the point of attachment is optionally substituted
  • K is CHR wherein R is selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl; E is selected from the group consisting of a covalent single bond, C(O)N(H), (H)NC(O), (R ? )NS(O) 2 , and S(O) 2 N(R 7 );
  • D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more
  • K is C, no more than one of D , D , J , and J
  • 5 6 5 6 5 6 5 6 5 6 5 6 is O, no more than one of D , D , J , and J is S, one of D , D , J , and J
  • R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl, alkyl sulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;
  • R and R are optionally Q with the proviso that no more than one
  • Q is selected from the group consisting of NR R , Q wherein Q is
  • R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino;
  • Q is selected from the group consisting of a single covalent bond,
  • W is selected from 1 through 3 and W is selected from the group consisting of
  • R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;
  • R and R are independently selected from the group consisting of hydrido, alkyl, and haloalkyl;
  • 38 R is optionally selected from the group consisting of aroyl and heteroaroyl; ss ss . ,. 14. 15.
  • Y° is optionally Q " -Q " wherein Q M is (CH(R ' " )) e - -wW 2"* --(CH(R )) h ,
  • e and h are integers independently selected from 1 through 2 and w 2
  • B is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment is optionally substituted 32 by R , the other carbon adjacent to the carbon at the point of attachment is
  • R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;
  • A is selected from the group consisting of single covalent bond and
  • W is selected from the group
  • R is selected from the group consisting of hydrido, hydroxy and alkyl
  • R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl; ⁇ is NH;
  • M is selected from the group consisting of N and R -C;
  • R is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo;
  • R 2 is Z°-Q;
  • Z is selected from the group consisting of a covalent single bond, O,
  • Q is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment is optionally substituted
  • R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulf onyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;
  • R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl, and cyano;
  • K is CH 2 ;
  • E° is C(O)N(H); Y° is formula (IV):
  • D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one is a covalent bond, K is C, no more than one of D , D , J , and J
  • 5 6 5 6 is optionally O, no more than one of D , D , J , and J is optionally S, one of
  • D , D , J , and J must be a covalent bond when two of D , D , J , and J
  • R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulf onyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;
  • R and R are optionally Q with the proviso that no more than one of
  • R and R is Q at the same time and that Q is Q ;
  • 21 23 24 and R is hydroxy at the same time and that no more than one of R and R is hydroxy at the same time;
  • R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy; s Q is selected from the group consisting of a single covalent bond,
  • a b J and J are each O;
  • B is optionally selected from the group consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group r 32 33 34 35 , 36 consisting of R , R , R , R , and R ;
  • R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;
  • A is selected from the group consisting of single covalent bond and
  • W is selected from the group
  • R is selected from the group consisting of hydrido, hydroxy and alkyl
  • R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;
  • R is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo;
  • R 2 is Z°-Q
  • Z is selected from the group consisting of a covalent single bond, O, S, NH, and CH 2 ;
  • Q is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment is optionally substituted
  • R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulf onyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;
  • R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, alkylenylamino, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl, and cyano; K is CH 2 ;
  • E° is C(O)N(H); Y° is formula (IV):
  • K is C, no more than one of D , D , J , and J
  • 5 6 5 6 5 6 5 6 5 6 5 6 is O, no more than one of D , D , J , and J is S, one of D , D , J , and J
  • R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulf onyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkylenylamino, and cyano;
  • R and R are optionally Q with the proviso that no more than one
  • R and R is Q at the same time and that Q is Q ;
  • Q is selected from the group consisting of NR R , Q wherein
  • R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy; Q is selected from the group consisting of a single covalent bond,
  • J and J are each O;
  • B is optionally selected from the group consisting of C3-C7 cycloalkyl and C4-C6 saturated heterocyclyl, wherein each ring carbon is optionally
  • a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon atom at the point of attachment are optionally
  • R 33 optionally substituted with R , and a ring carbon or nitrogen four atoms from
  • R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulf onyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;
  • R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, alkylenylamino, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl, and cyano;
  • R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy. hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;
  • A is selected from the group consisting of single covalent bond and
  • W is selected from the group
  • R is selected from the group consisting of hydrido, hydroxy and alkyl
  • R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;
  • R is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo;
  • R 2 is Z°-Q
  • Z is selected from the group consisting of a covalent single bond, O, S, NH, and CH 2 ;
  • Q is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment is optionally substituted
  • D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one is a covalent bond
  • K is C, no more than one of D , D , J , and J 5 6 5 6 .
  • . 5 6 5 6 is O, no more than one of D , D , J , and J is S, one of D , D , J , and J
  • R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;
  • R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulf onyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkylenylamino, and cyano;
  • R and R are optionally Q with the proviso that no more than one of
  • R and R is Q at the same time and that Q is Q ;
  • 21 23 24 and R is hydroxy at the same time and that no more than one of R and R is hydroxy at the same time;
  • R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy; g Q is selected from the group consisting of a single covalent bond,
  • J and J are each O;
  • B is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment is optionally substituted 32 by R , the other carbon adjacent to the carbon at the point of attachment is
  • R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;
  • A is selected from the group consisting of single covalent bond and
  • W is N(R );
  • R is selected from the group consisting of hydrido and alkyl
  • R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;
  • R is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo;
  • R 2 is Z°-Q;
  • Z is a covalent single bond;
  • Q is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment is optionally substituted
  • R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulf onyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;
  • 10 12 R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxyamido, and cyano;
  • K is CH 2 ;
  • E° is C(O)N(H);
  • D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one is a covalent bond, K is C, no more than one of D , D , J , and J
  • 5 6 5 6 5 6 5 6 5 6 5 6 is O, no more than one of D , D , J , and J is S, one of D , D , J , and J
  • R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulf onyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;
  • R and R are optionally Q with the proviso that no more than one of
  • R and R is Q at the same time and that Q is Q ;
  • Q is selected from the group consisting of NR R , Q wherein Q is
  • R , R , R , R , and R are independently selected from the group consisting of hydrido and alkyl;
  • Q s is CH 2 .
  • a b J and J are each O;
  • B is optionally selected from the group consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including
  • R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;
  • A is selected from the group consisting of single covalent bond and

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Abstract

L'invention concerne des composés d'uracyle d'hétéroaryle et d'aryle polycyclique substitués, utilisés en tant qu'inhibiteurs des sérines protéases de la coagulation en cascade, et des composés, des compositions et des méthodes d'anticoagulothérapie destinés au traitement et à la prévention d'une variété d'états thrombotiques notamment des maladies cérébrovasculaires et des artères coronaires.
PCT/US2000/008226 1999-05-19 2000-05-18 Anticoagulants a base d'uracils d'aryle polycycliques et d'heteroaryles WO2000069833A1 (fr)

Priority Applications (9)

Application Number Priority Date Filing Date Title
CA002373610A CA2373610A1 (fr) 1999-05-19 2000-05-18 Anticoagulants a base d'uracils d'aryle polycycliques et d'heteroaryles
MXPA01011806A MXPA01011806A (es) 1999-05-19 2000-05-18 Aril y heteroaril uracilos policiclicos sustituidos como agentes anticoagulantes.
BR0011273-9A BR0011273A (pt) 1999-05-19 2000-05-18 Uracilas de heteroarila e arila policìclica substituìdas como agentes anti-coagulantes
EP00931917A EP1178971A1 (fr) 1999-05-19 2000-05-18 Anticoagulants a base d'uracils d'aryle polycycliques et d'heteroaryles
AU49724/00A AU771740B2 (en) 1999-05-19 2000-05-18 Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents
NZ514877A NZ514877A (en) 1999-05-19 2000-05-18 Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents
US09/979,542 US6716838B1 (en) 1999-05-19 2000-05-18 Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents
JP2000618250A JP2002544263A (ja) 1999-05-19 2000-05-18 抗凝血剤としての置換多環式アリールおよびヘテロアリールウラシル
KR1020017014750A KR20010113969A (ko) 1999-05-19 2000-05-18 항응고제로서의 치환된 폴리시클릭 아릴 및 헤테로아릴우라실

Applications Claiming Priority (2)

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US13495799P 1999-05-19 1999-05-19
US60/134,957 1999-05-19

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WO2000069833A1 true WO2000069833A1 (fr) 2000-11-23

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PCT/US2000/008226 WO2000069833A1 (fr) 1999-05-19 2000-05-18 Anticoagulants a base d'uracils d'aryle polycycliques et d'heteroaryles

Country Status (14)

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EP (1) EP1178971A1 (fr)
JP (1) JP2002544263A (fr)
KR (1) KR20010113969A (fr)
CN (1) CN1152023C (fr)
AR (1) AR043677A1 (fr)
AU (1) AU771740B2 (fr)
BR (1) BR0011273A (fr)
CA (1) CA2373610A1 (fr)
MX (1) MXPA01011806A (fr)
NZ (1) NZ514877A (fr)
PE (1) PE20010217A1 (fr)
UY (1) UY26157A1 (fr)
WO (1) WO2000069833A1 (fr)
ZA (2) ZA200109338B (fr)

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WO2001087852A1 (fr) * 2000-05-18 2001-11-22 Pharmacia Corporation Uracils d'heteroaryle et d'aryle polycycliques substitues utiles pour l'inhibition selective de la cascade de coagulation
WO2001055119A3 (fr) * 2000-01-25 2002-02-14 Neurocrine Biosciences Inc Antagonistes du recepteur de la gonadoliberine et methodes associees
US6624180B2 (en) 2000-11-20 2003-09-23 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyridines useful for selective inhibition of the coagulation cascade
US6653316B1 (en) 1999-05-19 2003-11-25 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade
US6660885B2 (en) 2000-03-13 2003-12-09 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted benzenes useful for selective inhibition of the coagulation cascade
US6664255B1 (en) 1999-05-19 2003-12-16 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade
US6686484B2 (en) 2000-04-17 2004-02-03 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted 1,4-quinones useful for selective inhibition of the coagulation cascade
US6693121B2 (en) 2000-04-05 2004-02-17 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted 4-pyridones useful for selective inhibition of the coagulation cascade
US6710058B2 (en) 2000-11-06 2004-03-23 Bristol-Myers Squibb Pharma Company Monocyclic or bicyclic carbocycles and heterocycles as factor Xa inhibitors
US6716838B1 (en) 1999-05-19 2004-04-06 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents
US6750342B1 (en) 1999-05-19 2004-06-15 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade
US6867217B1 (en) 1999-05-19 2005-03-15 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade
US6875791B2 (en) 2000-04-05 2005-04-05 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted 4-pyrones useful for selective inhibition of the coagulation cascade
US6969715B2 (en) 2001-10-03 2005-11-29 Pharmacia Corporation 6-membered heterocyclic compounds useful for selective inhibition of the coagulation cascade
US7015230B1 (en) 1999-05-19 2006-03-21 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade
US7015223B1 (en) 2000-11-20 2006-03-21 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl 1,2,4-triazinones useful for selective inhibition of the coagulation cascade
US7105559B2 (en) 2001-10-03 2006-09-12 Pharmacia Corporation Substituted 5-membered polycyclic compounds useful for selective inhibition of the coagulation cascade
US7119094B1 (en) 2000-11-20 2006-10-10 Warner-Lambert Company Substituted polycyclic aryl and heteroarpyl pyrazinones useful for selective inhibition of the coagulation cascade
US7157470B2 (en) 2002-05-06 2007-01-02 Bristol-Myers Squibb Company Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors
US9522892B2 (en) 2011-11-29 2016-12-20 Perosphere Inc. Anticoagulant reversal agents

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AU2004200664B2 (en) * 2000-01-25 2007-08-16 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
GB0622472D0 (en) * 2006-11-10 2006-12-20 Addex Pharmaceuticals Sa Novel heterocyclic derivatives
CN116410143A (zh) * 2021-12-29 2023-07-11 杭州奥默医药股份有限公司 一种多取代脲嘧啶衍生物及其制备方法和应用

Citations (1)

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WO1996018644A1 (fr) * 1994-12-13 1996-06-20 Corvas International, Inc. Derives aromatiques heterocycliques utilisables comme inhibiteurs d'enzymes

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MXPA01011804A (es) * 1999-05-19 2003-09-04 Pharmacia Corp Aril y heteroaril pirimidinonas policiclicas sustituidas utiles como anticoagulantes.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996018644A1 (fr) * 1994-12-13 1996-06-20 Corvas International, Inc. Derives aromatiques heterocycliques utilisables comme inhibiteurs d'enzymes

Cited By (33)

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Publication number Priority date Publication date Assignee Title
US6716838B1 (en) 1999-05-19 2004-04-06 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents
US6870056B1 (en) 1999-05-19 2005-03-22 Pharmacia Corporation Substitituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade
US6458952B1 (en) 1999-05-19 2002-10-01 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade
US6867217B1 (en) 1999-05-19 2005-03-15 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade
US7015230B1 (en) 1999-05-19 2006-03-21 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade
US6653316B1 (en) 1999-05-19 2003-11-25 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade
US6750342B1 (en) 1999-05-19 2004-06-15 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade
US6664255B1 (en) 1999-05-19 2003-12-16 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade
US7462625B2 (en) 2000-01-25 2008-12-09 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
US7179815B2 (en) 2000-01-25 2007-02-20 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
KR100814269B1 (ko) * 2000-01-25 2008-03-18 뉴로크린 바이오사이언시즈 인코퍼레이티드 고나도트로핀-분비 호르몬 수용체 길항제 및 이를 포함하는 약제학적 조성물
US6608197B2 (en) 2000-01-25 2003-08-19 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
WO2001055119A3 (fr) * 2000-01-25 2002-02-14 Neurocrine Biosciences Inc Antagonistes du recepteur de la gonadoliberine et methodes associees
US6872728B2 (en) 2000-01-25 2005-03-29 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
US6660885B2 (en) 2000-03-13 2003-12-09 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted benzenes useful for selective inhibition of the coagulation cascade
US6852761B2 (en) 2000-03-13 2005-02-08 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted benzenes useful for selective inhibition of the coagulation cascade
US6693121B2 (en) 2000-04-05 2004-02-17 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted 4-pyridones useful for selective inhibition of the coagulation cascade
US6916847B2 (en) 2000-04-05 2005-07-12 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted 4-pyrones useful for selective inhibition of the coagulation cascade
US6875791B2 (en) 2000-04-05 2005-04-05 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted 4-pyrones useful for selective inhibition of the coagulation cascade
US6686484B2 (en) 2000-04-17 2004-02-03 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted 1,4-quinones useful for selective inhibition of the coagulation cascade
WO2001087852A1 (fr) * 2000-05-18 2001-11-22 Pharmacia Corporation Uracils d'heteroaryle et d'aryle polycycliques substitues utiles pour l'inhibition selective de la cascade de coagulation
US6710058B2 (en) 2000-11-06 2004-03-23 Bristol-Myers Squibb Pharma Company Monocyclic or bicyclic carbocycles and heterocycles as factor Xa inhibitors
US6951872B2 (en) 2000-11-06 2005-10-04 Bristol-Myers Squibb Pharma Company Monocyclic or bicyclic carbocycles and heterocycles as factor Xa inhibitors
US6624180B2 (en) 2000-11-20 2003-09-23 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyridines useful for selective inhibition of the coagulation cascade
US7119094B1 (en) 2000-11-20 2006-10-10 Warner-Lambert Company Substituted polycyclic aryl and heteroarpyl pyrazinones useful for selective inhibition of the coagulation cascade
US7015223B1 (en) 2000-11-20 2006-03-21 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl 1,2,4-triazinones useful for selective inhibition of the coagulation cascade
US6828338B2 (en) 2000-11-20 2004-12-07 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyridines useful for selective inhibition of the coagulation cascade
US7105559B2 (en) 2001-10-03 2006-09-12 Pharmacia Corporation Substituted 5-membered polycyclic compounds useful for selective inhibition of the coagulation cascade
US6969715B2 (en) 2001-10-03 2005-11-29 Pharmacia Corporation 6-membered heterocyclic compounds useful for selective inhibition of the coagulation cascade
US7157470B2 (en) 2002-05-06 2007-01-02 Bristol-Myers Squibb Company Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors
US7524863B2 (en) 2002-05-06 2009-04-28 Bristol-Myers Squibb Company Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors
US9522892B2 (en) 2011-11-29 2016-12-20 Perosphere Inc. Anticoagulant reversal agents
US9877961B2 (en) 2011-11-29 2018-01-30 Perosphere Inc. Anticoagulant reversal agents

Also Published As

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CN1152023C (zh) 2004-06-02
JP2002544263A (ja) 2002-12-24
AR043677A1 (es) 2005-08-10
AU4972400A (en) 2000-12-05
PE20010217A1 (es) 2001-03-07
AU771740B2 (en) 2004-04-01
ZA200400450B (en) 2004-09-29
KR20010113969A (ko) 2001-12-28
CA2373610A1 (fr) 2000-11-23
CN1351594A (zh) 2002-05-29
EP1178971A1 (fr) 2002-02-13
MXPA01011806A (es) 2003-09-04
ZA200109338B (en) 2004-05-26
UY26157A1 (es) 2000-12-29
BR0011273A (pt) 2002-06-18
NZ514877A (en) 2004-10-29

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