KR20010113969A - Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents - Google Patents

Abstract

The present invention provides substituted polycyclic aryl and heteroaryl uracil compounds useful as serine protease inhibitors of the coagulation cascade, and compounds, compositions and methods for anticoagulation therapy for the treatment and prevention of various thrombotic conditions including coronary and cerebrovascular diseases It is about.

Description

SUBSTITUTED POLYCYCLIC ARYL AND HETEROARYL URACILS AS ANTICOAGULATIVE AGENTS} Substituted polycyclic aryl and heteroaryl uracils as anticoagulants

In mammalian physiological systems, blood flow is regulated [Majerus, P. W. et al .: Anticoagulant, Thrombolytic, and Antiplatelet Drugs. Edited by Hardman, J. G. and Limbird, L. E. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th edition. New York, McGraw-Hill Book Co., 1996, pp. 1341-1343]. The blood must maintain fluidity in the vasculature, but it must be rapidly hemostatic in the damaged blood vessels to stop blood loss. Hemostasis or coagulation begins when platelets attach to macromolecules in the subcutaneous region of a primarily wounded and / or damaged blood vessel. These platelets aggregate to form primary hemostatic plugs and promote local activation of plasma coagulation factors, resulting in fibrin clots that strengthen aggregated platelets.

Plasma coagulation factors include factors II, V, VII, VIII, IX, X, XI and XII; these are also called protease enzyme sources. These coagulation factors or protease enzyme sources are activated by serine proteases, resulting in coagulation, called "coagulation cascades" or chain reactions [Handin, R. I .: Bleeding and Thrombosis. Wilson, J., et al .: Harrison's Principles of Internal Medicine. 12th Edition, New York, McGraw-Hill Book Co., 1991, p.350]. Coagulation or clotting occurs in two ways along different pathways. Endogenous or contact pathways result in a transition from XII to XIIa to XIa to IXa and from X to Xa. Xa, with the factor Va, converts prothrombin (II) to thrombin (IIa) to convert fibrinogen to fibrin. Fibrin polymerization results in fibrin clot. The exogenous pathway is initiated by the conversion of coagulation factor VII to VIIa by Xa. The presence of Tissue Factor and VIIa accelerates the formation of Xa in the presence of calcium ions and phospholipids. Formation of Xa produces thrombin, fibrin and fibrin clots as described above. The presence of one or more of these different coagulation factors and two different coagulation pathways may enable efficient and selective control and better understanding of the coagulation step portions.

Coagulation as a result of vascular damage is an important physiological step in mammals such as humans, but coagulation may also cause disease states. A pathological step called thrombus occurs when platelet aggregates and / or fibrin clots block (ie, occlude) blood vessels. Arterial thrombi can cause ischemic necrosis of the tissue that the artery supplied. If blood clots form in the coronary arteries, myocardial infarction or heart attack may occur. Blood clots generated in veins can cause swelling and inflammation in the tissues the veins have drained. Thrombosis of the deep veins can lead to complications with pulmonary embolism. Preventing or treating endovascular coagulation can be achieved by inhibition of blood platelet aggregation, inhibition of fibrin formation, inhibition of thrombus formation, inhibition of embolism, and unstable angina, refractory angina, myocardial infarction, transient ischemic attack, atrial It will be therapeutically useful to treat or prevent fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, intraocular fibrin accumulation, and reclosure or restenosis of reopened blood vessels.

There have been several reports of non-peptide and peptide-based uracil compounds that act as inhibitors of coagulation cascades or coagulation factors present in the coagulation process. US Pat. No. 5,656,645 (Tamura et al.) Discloses 4,5,6-substituted-3-aminopyridonyl-acetamide, 1,6-substituted-5, including amide substituents having formyl action and having activity on thrombin. -Aminouracinyl acetamide and 2,4-substituted-5-aminopyrimidinoyl-acetamide. US Pat. No. 5,658,930 (Tamura et al.) Again contains 4,5,6-substituted-3-aminopyridonyl-acetamide, 1,6-substituted-, including amide substituents having formyl action and having activity on thrombin. 5-aminouracinylacetamide and 2,4-substituted-5-aminopyrimidinoylacetamide are described. PCT patent applications 96/18644 and 97/46207, (Tamura et al.), Include 4,5,6-substituted-3-aminopyridonylacetamides, including amide substituents having formyl action and having activity on thrombin, Also described are 1,6-substituted-5-aminouracinyl-acetamide and 2,4-substituted-5-aminopyrimidinoyl acetamide.

[Overview of invention]

It is an object of the present invention to provide compounds which are beneficial for the treatment of anticoagulants and have the following structure:

It is another object of the present invention to provide a method for preventing and treating thrombotic conditions such as coronary artery disease, cerebrovascular disease and other coagulation related disorders. The thrombotic state is prevented and treated by administering an effective amount of a compound of formula I to a patient in need thereof.

Various other objects and advantages of the invention will become apparent from the following description of the invention.

The present invention belongs to the field of anticoagulant therapy and specifically relates to compounds, compositions and methods for the prevention and treatment of thrombotic conditions such as coronary artery disease and cerebrovascular disease. More specifically, the present invention relates to substituted polycyclic aryl and heteroaryl uracil compounds that inhibit the serine protease of the coagulation cascade.

The present invention provides a group of compounds comprising substituted polycyclic aryl and heteroaryl uracils represented by Formula I, useful for anticoagulant therapy for the treatment and prevention of various thrombotic conditions including coronary artery disease and cerebrovascular disease, or To pharmaceutically acceptable salts thereof:

[Formula I]

[Wherein;

J ^a and J ^b are independently selected from the group consisting of O and S;

J ^a is optionally selected from the group consisting of CH-R ⁶ and NR ⁶ (wherein R ⁶ is from the group consisting of R ^4a , R ^4b , R ¹⁴ , R ¹⁵ , R ³⁹ , R ⁴⁰ and R ⁵ ) A linear spacer moiety having from 1 to 4 adjacent atoms, connected to the point of attachment of the substituent selected to form a heterocyclyl ring having from 5 to 8 adjacent members;

J ^b is optionally selected from the group consisting of CH-R ⁶ and NR ⁶ , wherein R ⁶ is the point of attachment of a substituent selected from the group consisting of R ₁ , R ^4a , R ^4b , R ¹⁴ and R ¹⁵ A linear spacer moiety having from 1 to 4 adjacent atoms, connected to form a heterocyclyl ring having from 5 to 8 adjacent atoms;

J ^a and J ^b are optionally selected from the group consisting of CH-R ⁶ and NR ⁶ (wherein R ⁶ is connected to the bonding point of both R ^4a and R ^4b and has 5 to 8 adjacent circles) A linear spacer moiety having from 1 to 4 adjacent atoms, forming a heterocyclyl ring;

J ^a is optionally selected from the group consisting of CH-R ⁶ and NR ⁶ (wherein R ⁶ is heterocyclyl having 5 to 8 contiguous circles linked to the bond point of both R ³⁹ and R ⁴⁰ ) A linear spacer moiety having from 1 to 4 adjacent atoms, forming a ring;

B is of formula V:

Wherein D ¹ , D ² , J ¹ , J ² and K ¹ are independently selected from the group consisting of C, N, O, S and covalent bonds provided that at most one is a covalent bond and D ¹ , D ^{At least one of 2} , J ¹ , J ^2, and K ¹ is O, at most one of D ¹ , D ² , J ¹ , J ^2, and K ¹ is S, D ¹ , D ² , J ¹ , J ² and If two of K ¹ are O and S, then one of D ¹ , D ² , J ¹ , J ^2, and K ¹ must be covalent, and no more than four of D ¹ , D ² , J ¹ , J ^2, and K ¹ N, wherein R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently hydrido, acetami Diagram, haloacetamido, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy , Arloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl Aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N- Alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxy Kiel, haloalkoxyalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyl Oxy, halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl , Alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfon Ponylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfona Diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl , Alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroarkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, Cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, Alkylenylamino, hydroxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, Heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carbonalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carbon Boalkoxyalkyl, carboalkoxyalkenyl, carboxy, carboalkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, dialkoxyphosphono and diar Alkoxyphosphonoalkyl;

R ¹⁶ , R ¹⁹ , R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently and independently Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b simultaneously and Q ^b is Q ^be ;

Optionally, R ³² and R ³³ , R ³³ and R ³⁴ , R ³⁴ and R ³⁵ , and R ³⁵ and R ³⁶ are independently selected to form a spacer pair, wherein the spacer pairs together form a A group consisting of a cycloalkenyl ring having 5 to 8 contiguous members, a partially saturated heterocyclyl ring having 5 to 8 contiguous members, a heteroaryl ring having 5 to 6 contiguous members, and an aryl linking a point of attachment; To form a linear moiety having 3 to 6 adjacent atoms, forming a ring selected from: provided that the spacer pairs R ³² and R ³³ , R ³³ and R ³⁴ , R ³⁴ and R ³⁵ , and R ³⁵ and R ³⁶ In the group consisting of two or more are not used simultaneously);

Optionally R ⁹ and R ¹⁰ , R ¹⁰ and R ¹¹ , R ¹¹ and R ¹² and R ¹² and R ¹³ are independently selected to form a spacer pair (wherein the spacer pairs together form a A group consisting of a cycloalkenyl ring having 5 to 8 contiguous members, a partially saturated heterocyclyl ring having 5 to 8 contiguous members, a heteroaryl ring having 5 to 6 contiguous members, and an aryl linking a point of attachment; To form a linear moiety having 3 to 6 adjacent atoms, forming a ring selected from: provided that the spacer pairs R ⁹ and R ¹⁰ , R ¹⁰ and R ¹¹ , R ¹¹ and R ¹² , and R ¹² and R ¹³ In the group consisting of two or more are not used simultaneously);

B is optionally of formula VI:

Wherein D ³ , D ⁴ , J ³ and J ⁴ are independently selected from the group consisting of C, N, O and S, one or less of D ³ , D ⁴ , J ³ and J ⁴ is O, D ^{At least one of 3} , D ⁴ , J ^3, and J ⁴ is S, and at most three of D ¹ , D ² , J ^1, and J ² are N, wherein R ³² , R ³³ , R ^34, and R ³⁵ Are each independently selected to maintain the tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

B is optionally hydrido, trialkylsilyl, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkylenyl, C ₃ -C ₈ alkynyl, C ₂ -C ₈ halo Alkyl and C ₃ -C ₈ haloalkenyl (wherein each member of the group B is R ₃₂ , R ₃₃ , at any carbon atom up to six from the point of attachment of B to A, Optionally substituted with one or more of the group consisting of R ₃₄ , R ₃₅ and R ₃₆ ;

B is optionally selected from the group consisting of C ₃ -C ₁₅ cycloalkyl, C ₅ -C ₁₀ cycloalkenyl, C ₄ -C ₁₂ saturated heterocyclyl and C ₄ -C ₉ partially saturated heterocyclyl (wherein Each ring carbon is optionally substituted with R ³³ , except that the ring carbon except the ring carbon at the point of attachment of B to A is optionally substituted with oxo, provided that at least two ring carbons are not substituted at the same time with oxo, Ring carbon or nitrogen adjacent to the carbon atom is optionally substituted with R ⁹ or R ¹³ , and ring carbon or nitrogen adjacent to the R ⁹ position and two atoms away from the point of attachment is optionally substituted with R ¹⁰ , adjacent to and attached to the R ¹³ position Ring carbon or nitrogen two atoms away from the point is optionally substituted by R ¹² , and ring carbon or nitrogen adjacent to the R ¹⁰ position three atoms away from the point of attachment is optionally substituted by R ¹¹ , three atoms away from the point of attachment and R ¹² The ring carbon or nitrogen adjacent to the position is optionally substituted with R ³³ , four atoms away from the point of attachment and the ring carbon or nitrogen adjacent to the R ¹¹ and R ³³ positions is optionally substituted with R ³⁴ );

A is selected from the group consisting of a single covalent bond, (W ⁷ ) _rr- (CH (R ¹⁵ )) _pa and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr , wherein rr is 0 to 1 Is an integer selected from, pa is an integer selected from 0 to 6, W ⁷ is O, S, C (O), C (S), C (O) S, C (S) O, C (O) N (R ⁷ ), C (S) N (R ⁷ ), (R ⁷ ) NC (O), (R ⁷ ) NC (S), S (O), S (0) ₂ , S (0) ₂ N (R ⁷ ), (R ⁷ ) NS (0) ₂ , Se (O), Se (O) ₂ , Se (O) ₂ N (R ⁷ ), (R ⁷ ) NSe (O) ₂ , P ( O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), C (NR ⁷ ) N (R ⁷ ), (R ⁷ ) NC (NR ⁷ ), (R ⁷ ) NC (NR ⁷ ) NR ⁷ and N (R ⁷ ), provided that at least two in the group consisting of rr and pa are not zero at the same time;

R ⁷ and R ⁸ are independently 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, alkylsul Ponyalkyl, heteroaryl, heteroaryloxy, heteroarylamino, heteroaralkyl, heteroaralkyloxy, heteroaralkylamino and heteroaryloxyalkyl;

R ¹⁴ , R ¹⁵ , R ³⁷ , R ³⁸ , R ³⁹ , R ⁴⁰ , R ⁴¹ and R ⁴² are independently amidino, hydroxyamino, hydrido, hydroxy, halo, cyano, aryloxy, amino, Alkylamino, dialkylamino, hydroxyalkyl, aminoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alky Aryl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, Alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxy Alkyl, haloalkenyloxyalkyl, halocyclo Cooxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dica Leboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl , Arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsulfonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, hetero Arylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboalalcock Is selected from the group consisting of trialkylsilyl, dialkoxyphosphono, dialkoxyphosphono, dialkoxyphosphonoalkyl and dialkoxyphosphonoalkyl, provided that R ³⁷ and R ³⁸ are independently other than formyl Selected from one;

When R ¹⁴ and R ¹⁴ are bonded to different carbons, they are optionally taken together to form a covalent bond, alkylene, haloalkylene, and a cycloalkyl ring having 5 to 8 contiguous members, a cycloal having 5 to 8 contiguous members. To form a group selected from the group consisting of a kenyl ring and a linear partial spacer selected from the group consisting of heterocyclyl having 5 to 8 contiguous members;

When R ¹⁴ and R ¹⁵ are bonded to different carbons, they are optionally taken together to form a covalent bond, alkylene, haloalkylene, and a cycloalkyl ring having 5 to 8 contiguous members, a cycloal having 5 to 8 contiguous members To form a group selected from the group consisting of a kenyl ring and a linear partial spacer selected to form a ring selected from the group consisting of heterocyclyl having 5 to 8 adjacent members;

When R ¹⁵ and R ¹⁵ are bonded to different carbons, they are optionally taken together to form a covalent bond, alkylene, haloalkylene, and a cycloalkyl ring having 5 to 8 contiguous members, a cycloal having 5 to 8 contiguous members To form a group selected from the group consisting of a kenyl ring and a linear partial spacer selected from the group consisting of heterocyclyl having 5 to 8 contiguous members;

ψ is represented by NR ⁵ , O, C (O), C (S), S, S (O), S (O) ₂ , ON (R ⁵ ), P (O) (R ⁸ ) and CR ³⁹ R ⁴⁰ Selected from the group consisting of;

R ⁵ is hydrido, hydroxy, amino, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxy, alkoxy, alkoxy, alkenyloxy, alkylthio, arylthio, alkoxyalkyl, heteroaralkoxy Alkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyl Alkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, Heteroaryl, Heteroarylalkyl, Monocarboalkoxyalkyl, Monocarboalkoxy, Dicarboalkoxyalkyl, Monocarboxamido, Monocyanoalkyl, Dicyanoalkyl, Carboalkoxycyanoalkyl, Acyl, Ac Days, heterocyclic aroyl, heteroaryl is selected from the aryloxyalkyl and dialkoxy phosphine phono group consisting of alkyl;

When R ³⁹ and R ⁴⁰ are bonded to the same carbon, they are optionally taken together to form oxo, thiono, R ⁵ -N, alkylene, haloalkylene, and a cycloalkyl ring having 3 to 8 contiguous members, 3 to 8 Selected from the group consisting of a cycloalkenyl ring having 2 contiguous members, and a linear partial spacer having 2 to 7 contiguous atoms forming a ring selected from the group consisting of heterocyclyl rings having 3 to 8 contiguous members To form a group;

M is selected from the group consisting of N and R ¹ -C;

R ² and R ¹ are independently selected from the group consisting of Z ⁰ -Q, hydrido, alkyl, alkenyl and halo;

R ¹ is optionally amino, aminoalkyl, alkylamino, amidino, guanidino, hydroxy, hydroxyamido, alkoxy, hydroxyalkyl, alkoxyamino, thiol, alkylthio, dialkylsulfonium, trialkyl Phosphonium, dialkylsulfoniumalkyl, heteroarylamino, nitro, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxy Haloalkyl, cyano and phosphono;

R ² is optionally amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino, arylamino, aralkylamino, alkanoyl, Alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroarkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano and phosphono;

Optionally, R ² and R ^4a , R ² and R ^4b , R ² and R ¹⁴ , and R ² and R ¹⁵ are independently selected to form a spacer pair (wherein the spacer pair together form the spacer pair circle Linkages of to form a linear moiety having from 2 to 5 adjacent atoms to form a heterocyclyl ring having from 5 to 8 adjacent members, provided that R ² and R ^4a , R ² and R ^4b , R ^Two or more in the group of spacer pairs consisting of ² and R ¹⁴ , and R ² and R ¹⁵ are not used simultaneously);

Optionally R ² is independently selected to form a linear moiety having from 2 to 5 adjacent atoms connected to the bond point of both R ^4a and R ^4b to form a heterocyclyl ring having from 5 to 8 adjacent members Become;

Z ⁰ is a covalent single bond, (CR ⁴¹ R ⁴² ) _q (where q is an integer selected from 1 to 6), (CH (R ⁴¹ )) _g -W ^0- (CH (R ⁴² )) _p ( Wherein g and p are independently selected from ^0-3 , W ⁰ is O, S, C (O), C (S), C (O) O, C (S) O, C (O) S , C (S) S, C (O) N (R ⁴¹ ), (R ⁴¹ ) NC (O), C (S) N (R ⁴¹ ), (R ⁴¹ ) NC (S), OC (O) N (R ⁴¹ ), (R ⁴¹ ) NC (O) O, SC (S) N (R ⁴¹ ), (R ⁴¹ ) NC (S) S, SC (O) N (R ⁴¹ ), (R ⁴¹ ) NC (O) S, OC (S) N (R ⁴¹ ), (R ⁴¹ ) NC (S) O, N (R ⁴² ) C (O) N (R ⁴¹ ), (R ⁴¹ ) NC (O) N ( R ⁴² ), N (R ⁴² ) C (S) N (R ⁴¹ ), (R ⁴¹ ) NC (S) N (R ⁴² ), S (O), S (O) ₂ , S (O) ₂ N (R ⁴¹ ), N (R ⁴¹ ) S (O) ₂ , Se, Se (O), Se (O) ₂ , Se (O) ₂ N (R ⁴¹ ), N (R ⁴¹ ) Se (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ⁴¹ ), ON (R ⁴¹ ) and SiR ²⁸ R ²⁹ ) and (CH (R ⁴¹ )) _e -W ^22- (CH (R ⁴² )) _h (wherein e and h are independently selected from 0 to 2, and W ²² is ^{CR 41 = CR 42, CR 41} R 42 = C; vinylidene), ethynyl alkylpiperidinyl (C≡C; 1,2-ethynyl), 1,2-cyclopropene , 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholi Nilyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 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- Pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydrofuranyl, provided that R ⁴¹ And R ⁴² when directly bonded to N is selected from halo and other than cyano), and Z ⁰ directly bonds to the uracil ring;

R ²⁸ and R ²⁹ are independently hydrido, hydroxyalkyl, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, acyl, aroyl, aralkanoyl, heteroaroyl, alkoxyalkyl, Alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cyclo Alkyl alkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocyclo Alkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl, dicyanoalkyl, carbox Midoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyl, carboalkoxyalkyl, dicarboalkoxyalkyl, cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl, dicarboxamidocycloalkyl, carbo Alkoxycyanocycloalkyl, carboalkoxycycloalkyl, dicarboalkoxycycloalkyl, formylalkyl, acylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, aralkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl Alkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, dialkoxyphosphono, dialkoxyphosphono, dialkoxyphosphonoalkyl and dialkoxyphosphono Selected from the group consisting of alkyl;

R ²⁸ and R ²⁹ are optionally taken together such that a cycloalkyl ring having 2 to 7 contiguous atoms and having 3 to 8 contiguous members, a cycloalkenyl ring having 3 to 8 contiguous members, and 3 to 8 contiguous members To form a linear partial spacer forming a ring selected from the group consisting of a heterocyclyl ring having a circle;

Q is of formula II:

Wherein D ¹ , D ² , J ¹ , J ² and K ¹ are independently selected from the group consisting of C, N, O, S and covalent bonds, provided that one or less may be a covalent bond, and D ¹ And one or less of D ² , J ¹ , J ² and K ¹ may be O, one or less of D ¹ , D ² , J ¹ , J ² and K ¹ may be S, and D ¹ , D ² , If two of J ¹ , J ^2, and K ¹ are O and S, one of D ¹ , D ² , J ¹ , J ^2, and K ¹ must be a covalent bond, and D ¹ , D ² , J ¹ , J ^2, and Up to 4 of K ¹ may be N, wherein R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are each independently tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and oxygen 2 is chosen to maintain its properties;

Q is optionally selected from formula III:

Wherein D ³ , D ⁴ , J ³ and J ⁴ are independently selected from the group consisting of C, N, O and S, one or less of D ³ , D ⁴ , J ³ and J ⁴ is O, D ^{At least one of 3} , D ⁴ , J ^3, and J ⁴ is S, and at most three of D ¹ , D ² , J ^1, and J ² are N, wherein R ⁹ , R ¹⁰ , R ^11, and R ¹² are Each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

Q is optionally hydrido, alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl, partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cyclo Alkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halo Cycloalkoxyalkyl and halocycloalkenyloxyalkyl, provided that Z ⁰ is selected from other than a single covalent bond when Q is hydrido;

K is (CR ^4a R ^4b ) _n (wherein n is an integer selected from 1 to 4);

R ^4a and R ^4b are independently 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, alkylsulfonylalkyl, haloalkylsulfinyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl and aralkylsul is selected from the group consisting of alkyl sulfonyl, it provided that halo, hydroxy, cyano if play exists at the same time bonded to different carbon, R ^4a and R ^4b is the case that bonded to the carbon directly bonded to the uracil nitrogen hydroxyl Or cyano would outside the furnace;

R ^4a and R ^4b are optionally taken together when bonded to the same carbon, oxo, thiono, and a cycloalkyl ring having 3 to 8 contiguous members, a cycloalkenyl ring having 5 to 8 contiguous members, and 5 To form a group selected from the group consisting of linear spacer moieties having from 2 to 7 adjacent atoms to form a ring selected from the group consisting of heterocyclyl rings having from 8 to adjacent members, provided that common carbon is present in the uracil nitrogen R ^4a and R ^4b taken together when directly bonded are other than oxo or thiono;

E ⁰ is E ¹ when K is (CR ^4a R ^4b ) _n (wherein E ¹ is 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 ⁷ ), (R ⁷ ) NC (O), C (S) N (R ⁷ ), (R ⁷ ) NC (S), OC (O) N (R ⁷ ), (R ⁷ ) NC (O) O, SC (S) N (R ⁷ ), (R ⁷ ) NC (S) S, SC (O) N ( R ⁷ ), (R ⁷ ) NC (O) S, OC (S) N (R ⁷ ), (R ⁷ ) NC (S) O, N (R ⁸ ) C (O) N (R ⁷ ), ( R ⁷ ) NC (O) N (R ⁸ ), N (R ⁸ ) C (S) N (R ⁷ ), (R ⁷ ) NC (S) N (R ⁸ ), S (O), S (O ) ₂ , S (O) ₂ N (R ⁷ ), N (R ⁷ ) S (O) ₂ , S (O) ₂ N (R ⁷ ) C (O), C (O) N (R ⁷ ) S (O) ₂ , Se, Se (O), Se (O) ₂ , Se (O) ₂ N (R ⁷ ), N (R ⁷ ) Se (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ⁷ ), ON (R ⁷ ), SiR ²⁸ R ²⁹ , CR ^4a = R ^4b , Ethynylidene (C≡C; 1,2-ethynyl) and C═CR ^4a R ^4b );

K is optionally selected to be (CH (R ¹⁴ )) _j -T (wherein j is selected from an integer of 0 to 3, T is composed of a single covalent bond, O, S and N (R ⁷ ) Selected from the group wherein R ¹⁴ is other than hydroxy, cyano, halo, amino, alkylamino, dialkylamino and sulfhydryl when j is 1, and (CH (R ¹⁴ )) _j is a uracil ring Bound to);

E⁰Where K is (CH (R¹⁴))_j-T if optional²And (wherein E²Is a covalent single bond, C (O), C (S), C (O) O, C (S) O, C (O) S, C (S) S, C (O) N (R⁷), (R⁷NC (O), C (S) N (R⁷), (R⁷) NC (S), (R⁷) NC (O) O, (R⁷) NC (S) S, (R⁷NC (O) S, (R⁷NC (S) O, N (R⁸) C (O) N (R⁷), (R⁷NC (O) N (R⁸), N (R⁸C (S) N (R⁷), (R⁷NC (S) N (R⁸), S (O), S (O)₂, S (O)₂N (R⁷), N (R⁷S (O)₂, S (O)₂N (H) C (O), C (O) N (H) S (O)₂, Se (O), Se (O)₂, Se (O)₂N (R⁷), N (R⁷Se (O)₂, P (O) (R⁸), N (R⁷) P (O) (R⁸), P (O) (R⁸) N (R⁷) And N (R⁷) Selected from the group consisting of;

K is optionally selected to be G- (CH (R ¹⁵ )) _k (wherein _k is selected from integers from 1 to 3, G is selected from the group consisting of O, S and N (R ⁷ )) Provided that R ¹⁵ is other than hydroxy, cyano, halo, amino, alkylamino, dialkylamino and sulfhydryl when k is 1);

E ⁰ is optionally E ³ when K is G- (CH (R ¹⁵ )) _k (wherein E ³ is 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 ⁷ ), (R ⁷ ) NC (O), C (S) N (R ⁷ ) , (R ⁷ ) NC (S), OC (O) N (R ⁷ ), (R ⁷ ) NC (O) O, SC (S) N (R ⁷ ), (R ⁷ ) NC (S) S, SC (O) N (R ⁷ ), (R ⁷ ) NC (O) S, OC (S) N (R ⁷ ), (R ⁷ ) NC (S) O, N (R ⁸ ) C (O) N (R ⁷ ), (R ⁷ ) NC (O) N (R ⁸ ), N (R ⁸ ) C (S) N (R ⁷ ), (R ⁷ ) NC (S) N (R ⁸ ), S ( O), S (O) ₂ , S (O) ₂ N (R ⁷ ), N (R ⁷ ) S (O) ₂ , Se, Se (O), Se (O) ₂ , Se (O) ₂ N (R ⁷ ), N (R ⁷ ) Se (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ⁷ ), ON (R ⁷ ), SiR ²⁸ R ²⁹ , CR ^4a = CR ^4b , ethynylidene (C≡C; 1,2-ethynyl) and C = CR ^4a R ^4b Selected from the group);

Y ⁰ is of formula IV:

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond and K ² is independently C and Is selected from the group consisting of N ⁺ , at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S, D ⁵ , D ⁶ If two of, J ⁵ and J ⁶ are O and S, then one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be covalent, and if K ² is N ⁺ , D ⁵ , D ⁶ , J ⁵ and J ^When three or less of ⁶ are N and K ² is carbon, four or less of D ⁵ , D ⁶ , J ⁵ and J ⁶ are N, wherein R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are each independently And to maintain the tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

R ¹⁶ and R ¹⁷ are independently taken together optionally, a cycloalkenyl ring having 5 to 8 contiguous members, a partially saturated heterocyclyl ring having 5 to 8 contiguous members, a hetero having 5 to 6 contiguous members To form a linear partial spacer having 3 to 6 adjacent atoms connected to form a ring selected from the group consisting of aryl and aryl;

R ¹⁸ and R ¹⁹ are independently taken together optionally, a cycloalkenyl ring having 5 to 8 contiguous members, a partially saturated heterocyclyl ring having 5 to 8 contiguous members, hetero having 5 to 6 contiguous members To form a linear partial spacer having 3 to 6 adjacent atoms connected to form a ring selected from the group consisting of aryl and aryl;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , ⁺ NR ²⁰ R ²¹ R ²² , oxy, alkyl, aminoalkylenyl, alkylamino, dialkylamino, dialkylsulfoniumalkyl, acylamino and Q ^be Wherein Q ^be is hydrido and R ²⁰ , R ²¹ and R ²² are independently a group consisting of hydrido, amino, alkyl, hydroxy, alkoxy, aminoalkylenyl, alkylamino, dialkylamino and hydroxyalkyl Provided that at least two of R ²⁰ , R ²¹ and R ²² are not hydroxy, alkoxy, alkylamino, amino and dialkylamino at the same time and R ²⁰ , R ²¹ and R when K ² is N ^{+ 22} must be other than hydroxy, alkoxy, alkylamino, amino and dialkylamino);

Optionally, R ²⁰ and R ²¹ , R ²⁰ and R ²² , and R ²¹ and R ²² are independently selected to form a spacer pair (wherein the spacer pair together joins the joining points of the spacer pair circles) Forming a linear moiety having 4 to 7 contiguous atoms to form a heterocyclyl ring having 5 to 8 contiguous members, provided that the spacer pairs R ²⁰ and R ²¹ , R ²⁰ and R ²² , and R ²¹ and R Two or more in the group consisting of ²² are not used simultaneously);

Q ^b is optionally N (R ²⁶ ) SO ₂ N (R ²³ ) (R ²⁴ ), N (R ²⁶ ) C (O) OR ⁵ , N (R ²⁶ ) C (O) SR ⁵ , N (R ²⁶ ) C (S) OR ⁵ and N (R ²⁶ ) C (S) SR ⁵ , provided that two in the group consisting of R ²³ , R ²⁴ and R ²⁶ are bonded to the same atom, R One or less of ²³ , R ^24, and R ²⁶ may be hydroxy, alkoxy, alkyleneamino, alkylamino, amino, or dialkylamino);

Q^bIs optionally dialkylsulfonium, trialkylphosphonium, C (NR²⁵) NR²³R²⁴, N (R²⁶) C (NR²⁵) N (R²³) (R²⁴), N (R²⁶) C (O) N (R²³) (R²⁴), N (R²⁶C (S) N (R²³) (R²⁴), C (NR²⁵) OR⁵, C (O) N (R²⁶) C (NR²⁵) N (R²³) (R²⁴), C (S) N (R²⁶) C (NR²⁵) N (R²³) (R²⁴), N (R²⁶) N (R²⁶) C (NR²⁵) N (R²³) (R²⁴), ON (R²⁶) C (NR²⁵) N (R²³) (R²⁴), N (R²⁶) N (R²⁶SO₂N (R²³) (R²⁴), C (NR²⁵SR⁵, C (O) NR²³R²⁴And C (O) NR²³R²⁴R is selected from the group consisting of²³, R²⁴And R²⁶When any two of the group consisting of the same atom are attached²³, R²⁴And R²⁶At most one of which may be hydroxy, alkoxy, alkylamino, amino, or dialkylamino, wherein Q^bGroup directly bonds to a carbon atom);

R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkyleneamino, amino, alkylamino, dialkylamino and hydroxyalkyl;

R ²³ and R ²⁴ are optionally taken together to form a linear spacer moiety having 4 to 7 contiguous atoms connected to an attachment point forming a heterocyclyl ring having 5 to 8 contiguous circles;

Optionally, R ²³ and R ²⁵ , R ²⁴ and R ²⁵ , R ²⁵ and R ²⁶ , R ²⁴ and R ²⁶ , and R ²³ and R ²⁶ are independently selected to form a spacer pair (wherein the spacer pair is Together, taken at the point of attachment of the selected spacer pair to form an LUV group (wherein L, U and V are independently O, S, C (O), C (S), C (J _H ) ₂ S ( O), SO ₂ , OP (OR ³¹ ) R ³⁰ , P (O) R ³⁰ , P (S) R ³⁰ , C (R ³⁰ ) R ³¹ , C = C (R ³⁰ ) R ³¹ , (O) ₂ POP (O) ₂ , R ³⁰ (O) POP (O) R ³⁰ , Si (R ²⁹ ) R ²⁸ , Si (R ²⁹ ) R ²⁸ Si (R ²⁹ ) R ²⁸ , Si (R ²⁹ ) R ²⁸ OSi ( R ²⁹ ) R ²⁸ , (R ²⁸ ) R ²⁹ COC (R ²⁸ ) R ²⁹ , (R ²⁸ ) R ²⁹ CSC (R ²⁸ ) R ²⁹ , C (O) C (R ³⁰ ) = C (R ³¹ ), C (S) C (R ³⁰ ) = C (R ³¹ ), S (O) C (R ³⁰ ) = C (R ³¹ ), SO ₂ C (R ³⁰ ) = C (R ³¹ ), PR ³⁰ C ( R ³⁰ ) = C (R ³¹ ), P (O) R ³⁰ C (R ³⁰ ) = C (R ³¹ ), P (S) R ³⁰ C (R ³⁰ ) = C (R ³¹ ), DC (R ³⁰ ) (R ³¹ ) D, OP (OR ³¹ ) R ³⁰ , P (O) R ³⁰ , P (S) R ³⁰ , Si (R ²⁸ ) R ²⁹ and N (R ³⁰ ) and covalent bonds Provided that any two or less of L, U and V are simultaneously A bond, L, heterocyclyl consisting of U and V, having 5 to 10 contiguous circles));

D is selected from the group consisting of oxygen, C═O, C═S, S (O) _m (wherein m is an integer selected from 0 to 2);

J _H is independently selected from the group consisting of OR ²⁷ , SR ²⁷ and N (R ²⁰ ) R ²¹ ;

R ²⁷ is hydrido, alkyl, alkenyl, alkynyl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, Heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, Halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl , Arylsulfinylalkyl, arylsulfonylalkyl, cycloalkylsulfinylalkyl, cycloalkylsulfonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl and aralkylsulfonyl Selected from the group consisting of alkyl;

R ³⁰ and R ³¹ are independently hydrido, hydroxy, thiol, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, heteroaryloxyalkyl, alkoxy, alkylthio, arylthio, alkyl, alkenyl , Alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl , Alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, haloaralkylsulfinylalkyl, aralkylsulfonylalkyl, Cyanoalkyl, dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyl, carboalkoxyalkyl, dicarboalkoxyalkyl, cyanocycloalkyl, dicyanocycloalkyl, carboxamido Roalkyl, dicarboxamidocycloalkyl, carboalkoxycyanocycloalkyl, carboalkoxycycloalkyl, dicaralkoxycycloalkyl, formylalkyl, acylalkyl, dialkoxyphosphonoalkyl, dialkoxyphosphonoalkyl, Phosphonoalkyl, dialkoxyphosphonoalkoxy, dialkoxyphosphonoalkoxy, phosphonoalkoxy, dialkoxyphosphonoalkylamino, dialkoxyphosphonoalkylamino, phosphonoalkylamino, dialkoxyphosphonoalkyl, dialkoxy Phosphonoalkyl, Sulfonylalkyl, Alkoxysulfonylalkyl, Aralkoxysulfonylalkyl, Alkoxysulfonylalkoxy, Aralkoxysulfonylalkoxy, Sulfonylalkoxy, Alkoxysulfonylalkylamino, Aralkoxysulfonylalkylamino and Sulfonylalkyl Selected from the group consisting of amino;

R ³⁰ and R ³¹ are optionally taken together to form a cycloalkyl ring having 3 to 8 contiguous members, a cycloalkenyl ring having 3 to 8 contiguous members, and a heterocyclyl ring having 3 to 8 contiguous members To form a linear partial spacer having from 2 to 7 adjacent atoms forming a ring selected from the group consisting of:

Optionally, R ²³ and R ²⁵ , R ²⁴ and R ²⁵ , R ²⁵ and R ²⁶ , R ²⁴ and R ²⁶ , and R ²³ and R ²⁶ are independently selected to form a spacer pair (wherein the spacer pair is Together, taken at the point of attachment of the selected spacer pair to form an LUV group, wherein L, U and V are independently selected from the group of 1,2-disubstituted radicals consisting of a cycloalkyl radical, a cycloalkenyl radical, , Cycloalkyl and cycloalkenyl radicals are substituted with one or more groups selected from R ³⁰ and R ³¹ , aryl radicals, heteroaryl radicals, saturated heterocyclic radicals and partially saturated heterocyclic radicals, wherein 1,2 Substituents are independently C = O, C = S, C (R ²⁸ ) R ³² , S (O), S (O) ₂ , OP (OR ³¹ ) R ³⁰ , P (O) R ³⁰ , P (S ) R ³⁰ and Si (R ²⁸ ) R ²⁹ selected)));

Optionally, R ²³ and R ²⁵ , R ²⁴ and R ²⁵ , R ²⁵ and R ²⁶ , R ²⁴ and R ²⁶ , and R ²³ and R ²⁶ are independently selected to form a spacer pair (wherein the spacer pair is Together, taken at the point of attachment of the selected spacer pair to form an LUV group, wherein L, U and V are independently selected from the group consisting of 1,2-disubstituted alkylene radicals and 1,2-disubstituted alkenylene radicals Wherein the 1,2-substituents are independently C═O, C═S, C (R ²⁸ ) R ²⁹ , S (O), S (O) ₂ , OP (OR ³¹ ) R ³⁰ , P ( O) R ³⁰ , P (S) R ³⁰ and Si (R ²⁸ ) R ²⁹ wherein said alkylene and alkenylene radicals are substituted with one or more R ³⁰ or R ³¹ substituents)));

Q ^S is a single covalent bond, (CR ³⁷ R ³⁸ ) _b- (W ⁰ ) _az (wherein az is an integer selected from 0 to 1, b is an integer selected from 1 to 4, and W ⁰ is 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), OC (O) N (R ¹⁴ ), SC (S) N (R ¹⁴ ), SC (O) N (R ¹⁴ ), OC (S) N (R ¹⁴ ), N (R ¹⁵ ) C (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) N (R ¹⁵ ), N (R ¹⁵ ) C (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) N (R ¹⁵ ), S (O), S (O) ₂ , S (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) S (O) ₂ , Se, Se (O), Se (O) ₂ , Se (O) ₂ N (R ¹⁷ ), N (R ¹⁴ ) Se (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ¹⁴ ), ON (R ¹⁴ ) and SiR ²⁸ R ²⁹ ) , (CH (R ¹⁴ )) _c -W ^1- (CH (R ¹⁵ )) _d (wherein c and d are integers independently selected from 1 to 4, and W ¹ is 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), OC (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) O, SC (S) N (R ¹⁴ ), ( R ¹⁴ ) NC (S) S, SC (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) S, OC (S) N (R ^{1 4} ), (R ¹⁴ ) NC (S) O, N (R ¹⁵ ) C (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) N (R ¹⁵ ), N (R ¹⁵ ) C (S N (R ¹⁴ ), (R ¹⁴ ) NC (S) N (R ¹⁵ ), S (O), S (O) ₂ , S (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) S ( O) ₂ , Se, Se (O), Se (O) ₂ , Se (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) Se (O) ₂ , P (O) (R ⁸ ), N ( R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ¹⁴ ), ON (R ¹⁴ ), SiR ²⁸ R ²⁹ ) and ( CH (R ¹⁴ )) _e -W ^22- (CH (R ¹⁵ )) _h (wherein e and h are integers independently selected from 0 to 2, and W ²² is CR ⁴¹ = CR ⁴² , CR ⁴¹ R ⁴² = 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-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholi Neyl, 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-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2, Selected from the group consisting of 5-tetrahydrofuranyl and 3,4-tetrahydrofuranyl, provided that R ¹⁴ and R ¹⁵ are selected from other than halo and cyano when directly attached to N (CR ³⁷ R ³⁸ ) _b , (CH (R ¹⁴ )) _c , (CH (R ¹⁴ )) _e directly bonds to E ⁰ ;

R ³⁷ and R ³⁷ , when bonded to different carbons, are optionally taken together to form a cycloalkyl ring having 3 to 8 contiguous members, a cycloalkenyl ring having 3 to 8 contiguous members, and 3 to 8 contiguous members To form a linear partial spacer having 1 to 7 adjacent atoms to form a ring selected from the group consisting of heterocyclyl rings having:

R ³⁷ and R ³⁸ , when bonded to different carbons, are optionally taken together to form a cycloalkyl ring having 3 to 8 contiguous members, a cycloalkenyl ring having 3 to 8 contiguous members, and 3 to 8 contiguous members To form a linear partial spacer having 1 to 7 contiguous atoms to form a ring selected from the group consisting of heterocyclyl rings having:

R ³⁸ and R ³⁸ , when bonded to different carbons, are optionally taken together to form a cycloalkyl ring having 3 to 8 contiguous members, a cycloalkenyl ring having 3 to 8 contiguous members, and 3 to 8 contiguous members To form a linear partial spacer having 1 to 7 adjacent atoms to form a ring selected from the group consisting of heterocyclyl rings having:

R ³⁷ and R ³⁸ , when bonded to the same carbon, are optionally taken together to form oxo, thiono, alkylene, haloalkylene, and a cycloalkyl ring having 3 to 8 contiguous members, 3 to 8 contiguous circles; To form a group selected from the group consisting of a cycloalkenyl ring having and a linear partial spacer having from 2 to 7 adjacent atoms forming a ring selected from the group consisting of a heterocyclyl ring having from 3 to 8 adjacent members;

Y ⁰ is optionally Q ^b -Q ^ss (wherein Q ^ss is (CR ³⁷ R ³⁸ ) _f (where f is an integer selected from 1 to 6), (CH (R ¹⁴ )) _c- W ^1- (CH (R ¹⁵ )) _d (wherein c and d are integers independently selected from 1 to 4, and W ¹ is 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), OC (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) O, SC (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) S, SC (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) S, OC (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) O, N (R ¹⁵ ) C (O) N ( R ¹⁴ ), (R ¹⁴ ) NC (O) N (R ¹⁵ ), N (R ¹⁵ ) C (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) N (R ¹⁵ ), S (O ), S (O) ₂ , S (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) S (O) ₂ , Se, Se (O), Se (O) ₂ , Se (O) ₂ N ( R ¹⁴ ), N (R ¹⁴ ) Se (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ¹⁴ ), ON (R ¹⁴ ), SiR ²⁸ R ²⁹ ) and (CH (R ¹⁴ )) _e -W ^2- (CH (R ¹⁵ )) _h (wherein And h is an integer independently selected from 0 to 2, W ² is CR ^4a = CR ^4b , ethynylidene (C≡C; 1,2-ethynyl) And C = CR ^4a R ^4b , provided that R ¹⁴ and R ¹⁵ are selected from groups other than halo and cyano when directly bonded to N, and (CR ³⁷ R ³⁸ ) _f , (CH (R ¹⁵ )) _c and (CH (R ¹⁵ )) _e are directly bonded to E ⁰ , and when Q ^ss is (CR ³⁷ R ³⁸ ) _f (where f is other than integer 1) ), Q ^b is other than N (R ²⁶ ) N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) or ON (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) Selected from of;

Y ⁰ is optionally Q ^b -Q ^sss (wherein Q ^sss is (CH (R ³⁸ )) _r -W ³ , r is an integer selected from 1 to 3, and W ³ is 1,1- Cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclo Pentyl, 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, 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-pipe Ridinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl , 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl , 2H-2,5-pyranyl, 4H-2,3 -Pyranyl, 4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl, 4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl and 3,5-tetra Each carbon and hydrido-containing nitrogen source of the W ³ ring, which is selected from the group consisting of hydropyranyl and is other than the point of attachment, is optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , Provided that (CH (R ³⁸ )) _r binds to E ⁰ and Q ^b binds to the lowest number of substituent positions for each W ³ );

Y ⁰ is optionally Q ^b -Q ^sssr (wherein Q ^sssr is (CH (R ³⁸ )) _r -W ⁴ , r is an integer selected from 1 to 3, and W ⁴ is 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-pipera Genyl, 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, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5- Pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H- 2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4 -Yl, 2H-pyran-2-one-4,5-yl, 4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2 , 5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydro Each carbon and hydrido containing nitrogen source of the W ⁴ ring selected from the group consisting of pyranyl, 3,4-tetrahydropyranyl and 3,5-tetrahydropyranyl and having a point other than the point of attachment is R ⁹ , R ¹⁰ , Optionally substituted with one or more of the group consisting of R ¹¹ and R ¹² , provided that (CH (R ³⁸ )) _r binds to E ⁰ and Q ^b binds to the highest number of substituent positions for each W ⁴ );

Y ⁰ is optionally Q ^b -Q ^ssss (where Q ^ssss is (CH (R ³⁸ )) _r -W ⁵ , r is an integer selected from 1 to 3, and W ⁵ is 1,4- Indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4- Neyl, 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-benzothio Phenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-imidazo (1,2-a) pyridinyl, 2,5-imidazo (1,2-a) pyridinyl, 2,6-imidazo (1,2 -a) pyridinyl, 2,7-imidazo (1,2-a) pyridinyl, 3,4-imidazo (1,2-a) pyridinyl, 3,5-imidazo (1,2-a ) Pyridinyl, 3,6-imidazo (1,2-a) pyridinyl, 3,7-imidazo (1,2-a) pyridinyl, 2,4- Doryl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl , 1,4-isoindoleyl, 1,5-isoindoleyl, 1,6-isoindoleyl, 2,4-isoindoleyl, 2,5-isoindoleyl, 2,6-isoindoleyl, 2 , 7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl , 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3 , 7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2 , 5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl , 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3 , 8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1, 5-isoquinolinyl, 1,6 Isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl , 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- Isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cin Each carbon and hydrido-containing nitrogen source of the W ⁵ ring selected from the group consisting of nolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl and having a point other than the point of attachment Is optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , provided that Q ^b binds to the lowest number of substituent positions in each W ⁵ (CH (R ³⁸ )) _r is E Bound to ⁰ );

Y ⁰ is optionally Q ^b -Q ^ssssr (wherein Q ^ssssr is (CH (R ³⁸ )) _r -W ⁶ , r is an integer selected from 1 to 3, and W ⁶ is 1,4- Indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4- Neyl, 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-benzothio Phenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-imidazo (1,2-a) pyridinyl, 2,5-imidazo (1,2-a) pyridinyl, 2,6-imidazo (1,2 -a) pyridinyl, 2,7-imidazo (1,2-a) pyridinyl, 3,4-imidazo (1,2-a) pyridinyl, 3,5-imidazo (1,2-a ) Pyridinyl, 3,6-imidazo (1,2-a) pyridinyl, 3,7-imidazo (1,2-a) pyridinyl, 2,4- Doryl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl , 1,4-isoindoleyl, 1,5-isoindoleyl, 1,6-isoindoleyl, 2,4-isoindoleyl, 2,5-isoindoleyl, 2,6-isoindoleyl, 2 , 7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl , 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3 , 7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2 , 5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl , 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3 , 8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1, 5-isoquinolinyl, 1,6- Isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-iso Quinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnoly Each carbon and hydrido-containing nitrogen source of the W ⁶ ring, selected from the group consisting of nil, 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl, other than the point of attachment is Optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , provided that Q ^b binds to the highest number of substituent position in each W ⁶ (CH (R ³⁸ )) _r is E ⁰ Combined)].

In an embodiment of a compound of Formula (I) or a pharmaceutically acceptable salt thereof,

J ^a and J ^b are selected from the group consisting of O and S;

B is of formula V:

[Formula V]

Wherein D ¹ , D ² , J ¹ , J ² and K ¹ are independently selected from the group consisting of C, N, O, S and covalent bonds provided that at most one is a covalent bond and D ¹ , D ^{At least one of 2} , J ¹ , J ^2, and K ¹ is O, at most one of D ¹ , D ² , J ¹ , J ^2, and K ¹ is S, D ¹ , D ² , J ¹ , J ² and If two of K ¹ are O and S, then one of D ¹ , D ² , J ¹ , J ^2, and K ¹ must be covalent, and no more than four of D ¹ , D ² , J ¹ , J ^2, and K ¹ N, wherein R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen; ;

R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently hydrido, acetami Diagram, haloacetamido, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy , Arloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl Aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N- Alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxy Kiel, haloalkoxyalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyl Oxy, halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl , Alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfon Ponylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfona Diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl , Alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroarkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalkyl, alkylenedioxy, haloalkylenedioxy, Cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, Alkylenylamino, hydroxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, Heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carbonalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carbon Boalkoxyalkyl, carboalkoxyalkenyl, carboxy, carboalkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, dialkoxyphosphono and diar Alkoxyphosphonoalkyl;

R ¹⁶ , R ¹⁹ , R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently and independently Q ^b , provided that two R ¹⁶ and R ¹⁹ are not simultaneously Q ^b , and Q ^b is Q ^be ego;

Optionally, R ³² and R ³³ , R ³³ and R ³⁴ , R ³⁴ and R ³⁵ , and R ³⁵ and R ³⁶ are independently selected to form a spacer pair, wherein the spacer pairs together form a A group consisting of a cycloalkenyl ring having 5 to 8 contiguous members, a partially saturated heterocyclyl ring having 5 to 8 contiguous members, a heteroaryl ring having 5 to 6 contiguous members, and an aryl linking a bond point of To form a linear moiety having 3 to 6 adjacent atoms, forming a ring selected from: provided that the spacer pairs R ³² and R ³³ , R ³³ and R ³⁴ , R ³⁴ and R ³⁵ , and R ³⁵ and R ³⁶ In the group consisting of two or more may not be used simultaneously);

Optionally, R ⁹ and R ¹⁰ , R ¹⁰ and R ¹¹ , R ¹¹ and R ¹² , and R ¹² and R ¹³ are independently selected to form a spacer pair, wherein the spacer pairs together form the spacer pair A cycloalkenyl ring having 5 to 8 contiguous circles, a partially saturated heterocyclyl ring having 5 to 8 contiguous circles, a heteroaryl ring having 5 to 6 contiguous circles, and aryl Forming a linear moiety having 3 to 6 adjacent atoms, forming a ring selected from the group, provided that the spacer pairs R ⁹ and R ¹⁰ , R ¹⁰ and R ¹¹ , R ¹¹ and R ¹² , and R ¹² and R Two or more in the group consisting of ¹³ may not be used simultaneously);

B is optionally hydrido, trialkylsilyl, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkylenyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl, C ₂ -C ₈ halo Is selected from the group consisting of alkyl and C ₃ -C ₈ haloalkenyl, wherein each member of the group B is R ³² , R ³³ , Optionally substituted with one or more of the group consisting of R ³⁴ , R ³⁵ and R ³⁶ ;

B is optionally selected from the group consisting of C ₃ -C ₁₅ cycloalkyl, C ₅ -C ₁₀ cycloalkenyl, C ₄ -C ₁₂ saturated heterocyclyl and C ₄ -C ₉ partially saturated heterocyclyl, wherein And each ring carbon is optionally substituted with R ³³ , and the ring carbon except for the ring carbon at the point of attachment of B to A is optionally substituted with oxo, provided that two or more ring carbons are not simultaneously substituted with oxo, Ring carbon and nitrogen adjacent to the carbon atom of is optionally substituted with R ⁹ or R ¹³ , and ring carbon or nitrogen adjacent to the R ⁹ position and two atoms away from the point of attachment is optionally substituted with R ¹⁰ and adjacent to the R ¹³ position two atoms away from a ring carbon or nitrogen from the point of attachment is optionally substituted by R ^12, dropping three atoms from the point of attachment ring carbon or nitrogen adjacent to the R ¹⁰ position is optionally substituted with R ^11, dropping three atoms from the point of attachment R ¹² Optionally substituted at any, point of attachment is substituted with a ring carbon or nitrogen adjacent to the R ³³ value of four atoms falling R ¹¹ and R ³⁴ is a ring carbon or nitrogen adjacent to the R ³³ position);

A is selected from the group consisting of a single covalent bond, (W ⁷ ) _rr- (CH (R ¹⁵ )) _pa and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr , wherein rr is 0 to 1 Is an integer selected from, pa is an integer selected from 0 to 6, W ⁷ is O, S, C (O), C (S), C (O) S, C (S) O, C (O) N (R ⁷ ), C (S) N (R ⁷ ), (R ⁷ ) NC (O), (R ⁷ ) NC (S), S (O), S (0) ₂ , S (0) ₂ N (R ⁷ ), (R ⁷ ) NS (0) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), C (NR ⁷ ) N (R ⁷ ), (R ⁷ ) NC (NR ⁷ ), (R ⁷ ) NC (NR ⁷ ) NR ⁷ and N (R ⁷ ), provided that at least two of the group consisting of rr and pa are not zero at the same time);

R ⁷ and R ⁸ are independently selected from the group consisting of hydrido, hydroxy, alkyl, acyl, aroyl, heteroaroyl and alkoxyalkyl;

R ¹⁴ , R ¹⁵ , R ³⁷ and R ³⁸ are independently hydrido, hydroxy, halo, cyano, hydroxyalkyl, alkoxy, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloal Kenylalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxa Mead and carboxamidoalkyl;

R ¹⁴ and R ³⁸ can be independently selected from the group consisting of acyl, aroyl and heteroaroyl, provided that acyl is selected from something other than formyl;

ψ is represented by NR ⁵ , O, C (O), C (S), S, S (O), S (O) ₂ , ON (R ⁵ ), P (O) (R ⁸ ) and CR ³⁹ R ⁴⁰ Selected from the group consisting of;

R ⁵ is selected from the group consisting of hydrido, hydroxy, amino, alkyl, alkoxy, alkoxyalkyl, haloalkyl, acyl, aroyl and heteroaroyl;

R ³⁹ and R ⁴⁰ are independently hydrido, hydroxy, halo, cyano, hydroxyalkyl, acyl, aroyl, heteroaroyl, acylamido, alkoxy, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, Haloalkoxyalkyl, alkylsulfonyl, haloalkylsulfonyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide and carboxamidoalkyl;

M is selected from the group consisting of N and R ¹ -C;

R ² and R ¹ are independently selected from the group consisting of Z ⁰ -Q, hydrido, alkyl, alkenyl and halo;

R ¹ is optionally amino, aminoalkyl, alkylamino, amidino, guanidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, alkylthio, dialkylsulfonium, trialkylphosph Phonium, dialkylsulfoniumalkyl, heteroarylamino, nitro, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroarkanoyl, haloalkanoyl, hydroxyhalo Roalkyl, cyano and phosphono;

Z ⁰ is a covalent single bond, (CR ⁴¹ R ⁴² ) _q (where q is an integer selected from 1 to 6), (CH (R ⁴¹ )) _g -W ^0- (CH (R ⁴² )) _p ( Wherein g and p are integers independently selected from 0 to 3, and W ⁰ is O, S, C (O), C (S), C (O) O, C (S) O, C (O S, C (S) S, C (O) N (R ⁴¹ ), (R ⁴¹ ) NC (O), C (S) N (R ⁴¹ ), (R ⁴¹ ) NC (S), OC (O N (R ⁴¹ ), (R ⁴¹ ) NC (O) O, SC (S) N (R ⁴¹ ), (R ⁴¹ ) NC (S) S, SC (O) N (R ⁴¹ ), (R ⁴¹ NC (O) S, OC (S) N (R ⁴¹ ), (R ⁴¹ ) NC (S) O, N (R ⁴² ) C (O) N (R ⁴¹ ), (R ⁴¹ ) NC (O) N (R ⁴² ), N (R ⁴² ) C (S) N (R ⁴¹ ), (R ⁴¹ ) NC (S) N (R ⁴² ), S (O), S (O) ₂ , S (O) ₂ N (R ⁴¹ ), N (R ⁴¹ ) S (O) ₂ , Se, Se (O), Se (O) ₂ , Se (O) ₂ N (R ⁴¹ ), N (R ⁴¹ ) Se (O ) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ⁴¹ ), ON (R ⁴¹ ) And SiR ²⁸ R ²⁹ ) and (CH (R ⁴¹ )) _e -W ^22- (CH (R ⁴² )) _h (wherein e and h are integers independently selected from 0 to 2) And W ²² is CR ⁴¹ = CR ⁴² , CR ⁴¹ R ⁴² = C; vinylidene), ethynylidene (C≡C; 1,2-ethy Yl), 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-mor Polyyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 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 -Consisting of pyrrolidinyl, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydrofuranyl Selected from the group wherein R ⁴¹ and R ⁴² are selected from those other than halo and cyano when directly bonded to N, and Z ⁰ directly bonds to the uracil ring;

R ⁴¹ and R ⁴² are independently 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, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl, partially saturated hetero Cyclyl, heteroaryl, heteroaralkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfonyl, c Selected from roal kilsul sulfonyl, cycloalkyl-sulfonyl-alkyl, heteroaryl, alkyl sulfonyl, heteroaryl sulfonyl and aralkyl sulfonyl group consisting of alkyl and;

Q is of formula II:

[Formula II]

Wherein D ¹ , D ² , J ¹ , J ² and K ¹ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond and D ¹ , D ^{At least one of 2} , J ¹ , J ^2, and K ¹ is O, at most one of D ¹ , D ² , J ¹ , J ^2, and K ¹ is S, D ¹ , D ² , J ¹ , J ² and If two of K ¹ are O and S, one of D ¹ , D ² , J ¹ , J ^2, and K ¹ must be covalent, and no more than four of D ¹ , D ² , J ¹ , J ^2, and K ¹ Is N, wherein R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen Become;

Q is optionally selected from formula III:

[Formula III]

Wherein D ³ , D ⁴ , J ³ and J ⁴ are independently selected from the group consisting of C, N, O and S, one or less of D ³ , D ⁴ , J ³ and J ⁴ is O, D ^{At least one of 3} , D ⁴ , J ^3, and J ⁴ is S, and at most three of D ¹ , D ² , J ^1, and J ² are N, wherein R ⁹ , R ¹⁰ , R ^11, and R ¹² are Each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

Q is optionally hydrido, alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl, partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cyclo Alkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halo Cycloalkoxyalkyl and halocycloalkenyloxyalkyl, wherein Z ⁰ is selected from other than a single covalent bond when Q is hydrido;

K is (CR ^4a R ^4b ) _n (wherein n is an integer selected from 1 to 2);

R ^4a and R ^4b are independently halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl, alkoxyalkyl, aralkyl, heteroaralkyl, alkylthioalkyl, haloalkyl, haloalkenyl and Cyanoalkyl;

E ⁰ is E ¹ when K is (CR ^4a R ^4b ) _n (wherein E ¹ is 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 ⁷ ), (R ⁷ ) NC (O), C (S) N (R ⁷ ), (R ⁷ ) NC (S), OC (O) N (R ⁷ ), (R ⁷ ) NC (O) O, SC (S) N (R ⁷ ), (R ⁷ ) NC (S) S, SC (O) N ( R ⁷ ), (R ⁷ ) NC (O) S, OC (S) N (R ⁷ ), (R ⁷ ) NC (S) O, N (R ⁸ ) C (O) N (R ⁷ ), ( R ⁷ ) NC (O) N (R ⁸ ), N (R ⁸ ) C (S) N (R ⁷ ), (R ⁷ ) NC (S) N (R ⁸ ), S (O), S (O ) ₂ , S (O) ₂ N (R ⁷ ), N (R ⁷ ) S (O) ₂ , S (O) ₂ N (R ⁷ ) C (O), C (O) N (R ⁷ ) S (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ⁷ ), ON ( R ⁷ ), CR ^4a = R ^4b , ethynylidene (C≡C; 1,2-ethynyl) and C = CR ^4a R ^4b );

K is optionally (CH (R ¹⁴ )) _j -T (wherein j is selected from integers from 0 to 2, T is from a group consisting of a single covalent bond, O, S and N (R ⁷ )) (CH (R ¹⁴ )) _j is bonded to the uracil ring);

E⁰Where K is (CH (R¹⁴))_jE for -T²And (wherein E²Is a covalent single bond, C (O), C (S), C (O) O, C (S) O, C (O) S, C (S) S, C (O) N (R⁷), (R⁷NC (O), C (S) N (R⁷), (R⁷) NC (S), (R⁷) NC (O) O, (R⁷) NC (S) S, (R⁷NC (O) S, (R⁷NC (S) O, N (R⁸) C (O) N (R⁷), (R⁷NC (O) N (R⁸), N (R⁸C (S) N (R⁷), (R⁷NC (S) N (R⁸), S (O), S (O)₂, S (O)₂N (R⁷), N (R⁷S (O)₂, S (O)₂N (H) C (O), C (O) N (H) S (O)₂, P (O) (R⁸), N (R⁷) P (O) (R⁸), P (O) (R⁸) N (R⁷) And N (R⁷) Selected from the group consisting of;

K is optionally G- (CH (R ¹⁵ )) _k (wherein k is selected from integers from 1 to 2, G is selected from the group consisting of O, S and N (R ⁷ ), provided that R ¹⁵ is other than hydroxy, cyano, halo, amino, alkylamino, dialkylamino and sulfhydryl when k is 1);

E ⁰ is E ³ when K is G- (CH (R ¹⁵ )) _k (wherein E ³ is 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 ⁷ ), (R ⁷ ) NC (O), C (S) N (R ⁷ ), (R ⁷ ) NC (S), OC (O) N (R ⁷ ), (R ⁷ ) NC (O) O, SC (S) N (R ⁷ ), (R ⁷ ) NC (S) S, SC (O ) N (R ⁷ ), (R ⁷ ) NC (O) S, OC (S) N (R ⁷ ), (R ⁷ ) NC (S) O, N (R ⁸ ) C (O) N (R ⁷ ), (R ⁷ ) NC (O) N (R ⁸ ), N (R ⁸ ) C (S) N (R ⁷ ), (R ⁷ ) NC (S) N (R ⁸ ), S (O), S (O) ₂ , S (O) ₂ N (R ⁷ ), N (R ⁷ ) S (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ) , P (O) (R ⁸ ) N (R ⁷ ), N (R ⁷ ), ON (R ⁷ ), CR ^4a = CR ^4b , ethynylidene (C≡C; 1,2-ethynyl) and C = CR ^4a R ^4b );

Y ⁰ is of formula IV:

[Formula IV]

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond and K ² is independently C and Is selected from the group consisting of N ⁺ , at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S, D ⁵ , D ⁶ , in the case of J ⁵ and J ⁶ 2 dog O and S of D ^5, D ^6, J ⁵ and J ⁶ one must be a covalent bond when K ² is an N ⁺ D ^5, D ^6, J ^5, and J of ^When three or less of ⁶ are N and K ² is carbon, four or less of D ⁵ , D ⁶ , J ⁵ and J ⁶ are N, wherein R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are each independently And to maintain the tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

R ¹⁶ and R ¹⁷ are independently taken together optionally, a cycloalkenyl ring having 5 to 8 contiguous members, a partially saturated heterocyclyl ring having 5 to 8 contiguous members, a hetero having 5 to 6 contiguous members To form a linear partial spacer having 3 to 6 adjacent atoms, connected to a ring selected from the group consisting of aryl and aryl;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , ⁺ NR ²⁰ R ²¹ R ²² , oxy, alkyl, aminoalkylenyl, alkylamino, dialkylamino, dialkylsulfoniumalkyl, acylamino and Q ^be Wherein Q ^be is hydrido and R ²⁰ , R ²¹ and R ²² are independently from the group consisting of hydrido, amino, alkyl, hydroxy, alkoxy, aminoalkylenyl, alkylamino, dialkylamino and hydroxyalkyl Provided that at least two of R ²⁰ , R ²¹ and R ²² are not hydroxy, alkoxy, alkylamino, amino and dialkylamino at the same time and R ²⁰ , R ²¹ and R ²² when K ² is N ⁺ Must be other than hydroxy, alkoxy, alkylamino, amino and dialkylamino);

Optionally, R ²⁰ and R ²¹ , R ²⁰ and R ²² , and R ²¹ and R ²² are independently selected to form a spacer pair (wherein the spacer pair together joins the joining points of the spacer pair circles) Forming a linear moiety having 4 to 7 contiguous atoms to form a heterocyclyl ring having 5 to 8 contiguous members, provided that the spacer pairs R ²⁰ and R ²¹ , R ²⁰ and R ²² , and R ²¹ and R Two or more in the group consisting of ²² are not used simultaneously);

Q ^b is optionally N (R ²⁶ ) SO ₂ N (R ²³ ) (R ²⁴ ), N (R ²⁶ ) C (O) OR ⁵ , N (R ²⁶ ) C (O) SR ⁵ , N (R ²⁶ ) C (S) OR ⁵ and N (R ²⁶ ) C (S) SR ⁵ , provided that two of the groups consisting of R ²³ , R ²⁴ and R ²⁶ are bonded to the same atom, R ^At least one of ²³ , R ²⁴ and R ²⁶ is hydroxy, alkoxy, alkylamino, amino and dialkylamino);

Q^bIs optionally dialkylsulfonium, trialkylphosphonium, C (NR²⁵) NR²³R²⁴, N (R²⁶) C (NR²⁵) N (R²³) (R²⁴), N (R²⁶) C (O) N (R²³) (R²⁴), N (R²⁶C (S) N (R²³) (R²⁴), C (NR²⁵) OR⁵, C (O) N (R²⁶) C (NR²⁵) N (R²³) (R²⁴), C (S) N (R²⁶) C (NR²⁵) N (R²³) (R²⁴), N (R²⁶) N (R²⁶) C (NR²⁵) N (R²³) (R²⁴), ON (R²⁶) C (NR²⁵) N (R²³) (R²⁴), N (R²⁶) N (R²⁶SO₂N (R²³) (R²⁴), C (NR²⁵SR⁵, C (O) NR²³R²⁴And C (O) NR²³R²⁴R is selected from the group consisting of²³, R²⁴And R²⁶When two groups of the group are bonded to the same atom, R²³, R²⁴And R²⁶At most one of which may be hydroxy, alkoxy, alkylaminol, amino, or dialkylamino, wherein Q^bGroup directly bonds to a carbon atom);

R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, aminoalkylenyl, alkylamino, dialkylamino, amino and hydroxyalkyl;

R ²³ and R ²⁴ are optionally taken together to form a linear spacer moiety having from 4 to 7 adjacent atoms, connected to a point of attachment forming a heterocyclyl ring having from 5 to 8 adjacent members;

Q ^S is a single covalent bond, (CR ³⁷ R ³⁸ ) _b- (W ⁰ ) _az (wherein az is an integer selected from 0 to 1, b is an integer selected from 1 to 4, and W ⁰ is 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), OC (O) N (R ¹⁴ ), SC (S) N (R ¹⁴ ), SC (O) N (R ¹⁴ ), OC (S) N (R ¹⁴ ), N (R ¹⁵ ) C (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) N (R ¹⁵ ), N (R ¹⁵ ) C (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) N (R ¹⁵ ), S (O), S (O) ₂ , S (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) S (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ¹⁴ ), ON (R ¹⁴ )), (CH (R ¹⁴ )) _c -W ^1- (CH (R ¹⁵ )) _d (wherein c and d are independently integers selected from 1 to 4, W ¹ is 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), OC (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) O, SC (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) S, SC (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) S, OC (S) N (R ¹⁴ ), ( R ¹⁴ ) NC (S) O, N (R ¹⁵ ) C (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) N (R ¹⁵ ), N (R ¹⁵ ) C (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) N (R ¹⁵ ), S (O), S (O) ₂ , S (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) S (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ¹⁴ ), ON (R ¹⁴ )) and (CH (R ¹⁴ )) _e -W ^22- (CH (R ¹⁵ )) _h , wherein e and h are independently selected from 0 to 2, and W ²² is CR ⁴¹ = CR ⁴² , CR ⁴¹ R ⁴² = 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-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholi Neyl, 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-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2, Selected from the group consisting of 5-tetrahydrofuranyl and 3,4-tetrahydrofuranyl, provided that R ¹⁴ and R ¹⁵ are selected from other than halo and cyano when directly attached to N (CR ³⁷ R ³⁸ ) _b , (CH (R ¹⁴ )) _c , (CH (R ¹⁴ )) _e binds to E ⁰ ;

Y ⁰ is optionally Q ^b -Q ^ss (wherein Q ^ss is (CR ³⁷ R ³⁸ ) _f (where f is an integer selected from 1 to 6), (CH (R ¹⁴ )) _c- W ^1- (CH (R ¹⁵ )) _d (wherein c and d are integers independently selected from 1 to 4, and W ¹ is 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), OC (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) O, SC (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) S, SC (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) S, OC (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) O, N (R ¹⁵ ) C (O) N ( R ¹⁴ ), (R ¹⁴ ) NC (O) N (R ¹⁵ ), N (R ¹⁵ ) C (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) N (R ¹⁵ ), S (O ), S (O) ₂ , S (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) S (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ¹⁴ ), ON (R ¹⁴ )) and (CH (R ¹⁴ )) _e -W ^2- (CH ( R ¹⁵ )) _h (wherein e and h are integers independently selected from 0 to 2, W ² is CR ^4a = CR ^4b , ethynylidene (C≡C; 1,2-ethynyl) and C = CR ^4a is selected from the group consisting of R ^4b , provided that R ¹⁴ and R ¹⁵ are selected from the group other than halo and cyano when directly bonded to N, and (CR ³⁷ R ³⁸ ) _f , (CH (R ¹⁴ )) _c and (CH (R ¹⁴ ) _e is bound to E ⁰ );

Y ⁰ is optionally Q ^b -Q ^sss (wherein Q ^sss is (CH (R ³⁸ )) _r -W ³ , r is an integer selected from 1 to 3, and W ³ is 1,1- Cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclo Pentyl, 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, 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-pipe Ridinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl , 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl , 2H-2,5-pyranyl, 4H-2,3 -Pyranyl, 4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl, 4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl and 3,5-tetra Each carbon and hydrido-containing nitrogen source of the W ³ ring, which is selected from the group consisting of hydropyranyl and is other than the point of attachment, is optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , Provided that (CH (R ³⁸ )) _r binds to E ⁰ and Q ^b binds to the lowest number of substituent positions for each W ³ );

Y ⁰ is optionally Q ^b -Q ^sssr (wherein Q ^sssr is (CH (R ³⁸ )) _r -W ⁴ , r is an integer selected from 1 to 3, and W ⁴ is 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-pipera Genyl, 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, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5- Pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H- 2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4 -Yl, 2H-pyran-2-one-4,5-yl, 4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2 , 5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydro Each carbon and hydrido containing nitrogen source of the W ⁴ ring selected from the group consisting of pyranyl, 3,4-tetrahydropyranyl and 3,5-tetrahydropyranyl and having a point other than the point of attachment is R ⁹ , R ¹⁰ , Optionally substituted with one or more of the group consisting of R ¹¹ and R ¹² , provided that (CH (R ³⁸ )) _r binds to E ⁰ and Q ^b binds to the highest number of substituent positions for each W ⁴ );

Y ⁰ is optionally Q ^b -Q ^ssss (where Q ^ssss is (CH (R ³⁸ )) _r -W ⁵ , r is an integer selected from 1 to 3, and W ⁵ is 1,4- Indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4- Neyl, 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-benzothio Phenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,7-imidazo (1,2-a) pyridinyl, 3,4-imidazo (1,2-a) pyridinyl, 3,5-imidazo (1,2 -a) pyridinyl, 3,6-imidazo (1,2-a) pyridinyl, 3,7-imidazo (1,2-a) pyridinyl, 2,4-indolyl, 2,5-indole Reel, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indole , 1,4-isoindoleyl, 1,5-isoindoleyl, 1,6-isoindoleyl, 2,4-isoindoleyl, 2,5-isoindoleyl, 2,6-isoindoleyl, 2 , 7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl , 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3 , 7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2 , 5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl , 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3 , 8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1, 5-isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5-isoquinol Neyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7 Isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8 -W ⁵ ring selected from the group consisting of cinnaolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl, other than the point of attachment Each carbon and hydrido containing nitrogen source of is optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , provided that Q ^b is bonded to the lowest number of substituent positions of each W ⁵ , (CH (R ³⁸ )) _r binds to E ⁰ );

Y ⁰ is optionally Q ^b -Q ^ssssr (wherein Q ^ssssr is (CH (R ³⁸ )) _r -W ⁶ , r is an integer selected from 1 to 3, and W ⁶ is 1,4- Indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4- Neyl, 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-benzothio Phenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,7-imidazo (1,2-a) pyridinyl, 3,4-imidazo (1,2-a) pyridinyl, 3,5-imidazo (1,2 -a) pyridinyl, 3,6-imidazo (1,2-a) pyridinyl, 3,7-imidazo (1,2-a) pyridinyl, 2,4-indolyl, 2,5-indole Reel, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-phosphoryl Reel, 1,4-isoindoleyl, 1,5-isoindoleyl, 1,6-isoindoleyl, 2,4-isoindoleyl, 2,5-isoindoleyl, 2,6-isoindoleyl, 2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxa Zolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinoli Nilyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1 , 5-isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5-isoquinol Linyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7 Isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8 A W ⁶ ring selected from the group consisting of cinnaolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl, other than the point of attachment Each carbon and hydrido containing nitrogen source of is optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , provided that Q ^b is bonded to the highest number of substituent positions of each W ⁶ , (CH (R ²³⁸ )) _r binds to E ⁰ ).

In another embodiment of a compound of Formula (I) or a pharmaceutically acceptable salt thereof,

J ^a and J ^b are independently selected from the group consisting of O and S;

B is of formula V:

[Formula V]

Wherein D ¹ , D ² , J ¹ , J ² and K ¹ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, D ¹ , D ² At least one of J ¹ , J ² and K ¹ is O, at most one of D ¹ , D ² , J ¹ , J ² and K ¹ is S, and D ¹ , D ² , J ¹ , J ² and K ^If two of ¹ are O and S, one of D ¹ , D ² , J ¹ , J ^2, and K ¹ must be covalent, and no more than four of D ¹ , D ² , J ¹ , J ^2, and K ¹ Is N;

R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, Haloacetamido, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryl Roylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, ar Alkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino , Heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloal Cooxyalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halo Cycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsul Finyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, Alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diaryl Midosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, Aroyl, heteroaroyl, aralkanoyl, heteroarkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalkyl, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cyclo Alkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, alkylenylamino, Hydroxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryl Oxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carbonalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carbonalkoxy Alkyl, carboalkoxyalkenyl, carboxy, carboalkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, dialkoxyphosphono and diaalkoxyphosph Independently selected from the group consisting of phonoalkyl;

R ¹⁶ , R ¹⁹ , R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently and independently Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b simultaneously and Q ^b is Q ^be ;

B is optionally hydrido, trialkylsilyl, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkylenyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl, C ₂ -C ₈ halo Is selected from the group consisting of alkyl and C ₃ -C ₈ haloalkenyl, wherein each member of group B is selected for A with one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ Optionally substituted at most 6 carbon atoms from the point of attachment of B;

B is optionally selected from the group consisting of C ₃ -C ₁₂ cycloalkyl, C ₅ -C ₁₀ cycloalkenyl and C ₄ -C ₉ saturated heterocyclyl, wherein each ring carbon is optionally substituted with R ³³ , Ring carbons other than the ring carbon at the point of attachment of B to A are optionally substituted with oxo, provided that at least two ring carbons are not substituted at the same time with oxo, and that ring carbon and nitrogen adjacent to the carbon atom at the point of attachment are R Ring carbon or nitrogen optionally substituted with ⁹ or R ¹³ and adjacent to R ⁹ and 2 atoms away from the point of attachment ring carbon or nitrogen optionally substituted with R ¹⁰ and adjacent with R ¹³ and 2 atoms away from the point of attachment nitrogen being optionally substituted with R ^12, falling to three atoms from the point of attachment ring carbon or nitrogen adjacent to the R ¹⁰ position is optionally substituted with R ^11, falling to three atoms from the point of attachment ¹² where R Adjacent ring carbon or nitrogen, optionally substituted with R ^33, dropping to four atoms from the point of attachment ring carbon or nitrogen adjacent to the R ¹¹ and R ³³ position is optionally substituted with R ^34;

A is a single covalent bond, (W ⁷ ) _rr- (CH (R ¹⁵ )) _pa and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (where rr is an integer selected from 0 to 1, pa is an integer selected from 0 to 6, and W ⁷ is 0, S, C (O), C (O) N (R ⁷ ), C (S) N (R ⁷ ), (R ⁷ ) NC (O ), (R ⁷ ) NC (S) and N (R ⁷ ), provided that at least two of the groups consisting of rr and pa cannot be 0 at the same time;

R ⁷ and R ⁸ are independently selected from the group consisting of hydrido, hydroxy, alkyl and alkoxyalkyl;

R ¹⁴ , R ¹⁵ , R ³⁷ and R ³⁸ are independently selected from the group consisting of hydrido, hydroxy, halo, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy and haloalkoxyalkyl;

R ¹⁴ and R ³⁸ are independently selected from the group consisting of aroyl and heteroaroyl;

Ψ is selected from the group consisting of NR ⁵ , C (O) and S (O) ₂ ;

R ⁵ is selected from the group consisting of hydrido, hydroxy, alkyl and alkoxy;

R ³⁹ and R ⁴⁰ are independently selected from the group consisting of hydrido, hydroxy, halo, hydroxyalkyl, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy and haloalkoxyalkyl;

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio, amino, aminoalkyl, alkylamino, amidino, guanidino, hydroxy, hydroxyamino, alkoxy , Hydroxyalkyl, alkoxyamino, thiol, alkylthio and phosphono;

R ² is Z ⁰ -Q;

Z ⁰ is a covalent single bond, (CR ⁴¹ R ⁴² ) _q (where q is an integer selected from 1 to 3), (CH (R ⁴¹ )) _g -W ^0- (CH (R ⁴² )) _p ( Wherein g and p are integers independently selected from 0 to 3, and W ⁰ is 0, S, C (O), S (O), S (O) ₂ , N (R ⁴¹ ) and ON (R ⁴¹ ) and (CH (R ⁴¹ )) _e -W ^22- (CH (R ⁴² )) _h (wherein e and h are integers independently selected from 0 to 2, and W ²² CR ⁴¹ = CR ⁴² , 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2 , 3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3 -Piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-pipe Ridinyl, 2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-py Ridinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4- Selected from the group consisting of tetrahydrofuranyl), provided Z ⁰ is directly bonded to the uracil ring;

R ⁴¹ and R ⁴² are independently selected from the group consisting of amidino, hydroxyamino, hydrido, hydroxy, amino and alkyl;

Q is hydrido (Z ⁰ excluding covalent single bond), and is selected from the group consisting of Formula II:

[Formula II]

Wherein D ¹ , D ² , J ¹ , J ² and K ¹ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, D ¹ , D ² At least one of J ¹ , J ² and K ¹ is O, at most one of D ¹ , D ² , J ¹ , J ² and K ¹ is S, and D ¹ , D ² , J ¹ , J ² and K ^If two of ¹ are O and S, one of D ¹ , D ² , J ¹ , J ^2, and K ¹ must be covalent, and no more than four of D ¹ , D ² , J ¹ , J ^2, and K ¹ Is N, provided that R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen, ;

K is (CR ^4a R ^4b ) _n (wherein n is an integer selected from 1 to 2);

R ^4a and R ^4b are independently selected from the group consisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl and haloalkyl;

E ⁰ is a covalent single bond, C (O), C (S), C (O) N (R ⁷ ), (R ⁷ ) NC (O), S (O) ₂ , (R ⁷ ) NS (O) ₂ and S (O) ₂ N (R ⁷ );

Y ⁰ is formula IV:

[Formula IV]

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, K ² is C, D ⁵ At least one of D ⁶ , J ⁵ and J ⁶ is O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S, two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and For S one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be a covalent bond, and if K ² is carbon, up to 4 of D ⁵ , D ⁶ , J ⁵ and J ⁶ are N, provided that ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

Q ^b is NR ²⁰ R ²¹ , ⁺ NR ²⁰ R ²¹ R ²² , aminoalkylenyl and Q ^be (wherein Q ^be is hydrido and R ²⁰ , R ²¹ and R ²² are hydrido, alkyl, hydroxy , Amino, aminoalkylenyl, dialkylamino, alkylamino and hydroxyalkyl, provided that two R ²⁰ and R ²¹ are not hydroxy, amino, alkylamino or dialkylamino at the same time). Selected from the group consisting of;

Q ^b is optionally C (NR ²⁵ ) NR ²³ R ²⁴ , N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ), C (O) N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ), N (R ²⁶ ) N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) and ON (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴⁾ is selected from the group consisting of, with the proviso that R ^23, R ²⁴ and, if R ^26, two of the groups attached to the same atom consisting of, R ^23, R ²⁴ and R a or less of the ²⁶ is hydroxy, alkylamino , Amino or dialkylamino;

R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, alkylenylamino, dialkylamino, alkylamino and hydroxyalkyl;

Q ^s is a single covalent bond, (CR ³⁷ R ³⁸ ) _b- (W ⁰ ) _az (where az is an integer selected from 0 to 1, b is an integer selected from 1 to 5, and W ⁰ is 0 , C (O), S (O), S (O) ₂ , S (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) S (O) ₂ and N (R ¹⁴ ) , (CH (R ¹⁴ )) _c -W ^1- (CH (R ¹⁵ )) _d (wherein c and d are integers independently selected from 1 to 4, and W ¹ is 0, 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), OC (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) O, SC (S) N (R ¹⁴ ), ( R ¹⁴ ) NC (S) S, SC (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) S, OC (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S) O, N (R ¹⁵ ) C (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) N (R ¹⁵ ), N (R ¹⁵ ) C (S) N (R ¹⁴ ), (R ¹⁴ ) NC (S N (R ¹⁵ ), S (O), S (O) ₂ , S (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) S (O) ₂ , P (O) (R ⁸ ), N (R ⁷ ) P (O) (R ⁸ ), P (O) (R ⁸ ) N (R ⁷ ), N (R ¹⁴ ), ON (R ¹⁴ ) selected from the group consisting of) and (CH (R ¹⁴ )) _e -W ^22- (CH (R ¹⁵ )) _h (wherein e and h are independently selected from 0 to 2) Is an integer selected, W ²² is CR ⁴¹ = CR ⁴² , CR ⁴¹ R ⁴² = 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-morpholinyl, 2 , 6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 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-pipe Ridinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl , 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydrofuranyl, provided that when directly attached to N R ¹⁴ and R ¹⁵ are selected from other than halo and cyano, (CR ³⁷ R ³⁸ ) _b , ( CH (R ¹⁴ )) _c and (CH (R ¹⁴ )) _e is bonded to E ⁰ );

Y ⁰ is optionally Q ^b -Q ^ss (where Q ^ss is (CR ³⁷ R ³⁸ ) _f (where f is an integer selected from 1 to 4), (CH (R ¹⁴ )) _c -W ^1- (CH (R ¹⁵ )) _d (wherein c and d are integers independently selected from 1 to 2, and W ¹ is 0, S, C (O), C (O) N (R ¹⁴ ) , (R ¹⁴ ) NC (O), N (R ¹⁵ ) C (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O) N (R ¹⁵ ), N (R ¹⁴ ), ON (R ¹⁴ ) Selected from the group consisting of (CH (R ¹⁴ )) _e -W ^2- (CH (R ¹⁵ )) _h (wherein e and h are integers independently selected from 0 to 2, and W ² is CR) ^4a = CR ^4b , ethynylidene (C≡C; 1,2-ethynyl) and C = CR ^4a R ^4b , provided that when bonded directly to N, R ¹⁴ and R ¹⁵ are other than halo Selected from the group consisting of (CR ³⁷ R ³⁸ ) _f , (CH (R ¹⁴ )) _c and (CH (R ¹⁴ )) _e is bonded to E ⁰ );

Y ⁰ is optionally Q ^b -Q ^sss (wherein, Q ^sss is (CH (R ³⁸ )) _r -W ³ (r is an integer selected from 1 to 2, W ³ is 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, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-pipe Ferrazinyl, 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, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2 , 3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H -2,5-pyranyl, 4H-2,3-pyranyl, 4H-2, 4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl, 4H-pyran-4-one- 2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl , 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl and 3,5-tetrahydropyranyl And each carbon and hydrido-containing nitrogen source of the ring of W ³ other than the point of attachment is optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , provided that (CH (R ³⁸ )) _r is bonded to E ⁰ and Q ^b is bonded to the lowest number of substituent positions in each W ³ );

Y ⁰ is optionally Q ^b -Q ^{sssr wherein} Q ^sssr is (CH (R ³⁸ )) _r -W ⁴ (r is an integer selected from 1 to 2, and W ⁴ is 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, 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-piperidin Nilyl, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4- Pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2 -One-4,5-yl, 4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetra Selected from the group consisting of hydropyranyl and 3,5-tetrahydropyranyl, and each carbon and hydrido containing nitrogen source of the ring of W ⁴ other than the point of attachment is R ⁹ , R ¹⁰ , R ¹¹ and R ¹² Optionally substituted with one or more of the group consisting of (CH (R ³⁸ )) _r is bonded to E ⁰ , and Q ^b is bonded to the highest number of substituent positions of each W ⁴ );

Y ⁰ is optionally Q ^b -Q ^ssss (where Q ^ssss is (CH (R ³⁸ )) _r -W ⁵ (r is an integer selected from 1 to 2, and W ⁵ is 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-benzofura Nilyl, 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, 2,7-imidazo (1,2-a) pyridinyl, 3,4-imidazo (1,2-a) pyridinyl, 3,5-imidazo (1,2-a ) Pyridinyl, 3,6-imidazo (1,2-a) pyridinyl, 3,7-imidazo (1,2-a) pyridinyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoin Doryl, 1,5-isoindoleyl, 1,6-isoindoleyl, 2,4-isoindoleyl, 2,5-isoindoleyl, 2,6-isoindoleyl, 2,7-isoindoleyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzone company Zolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2 , 6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolin Nilyl, 2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-iso Nolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4, 8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5 Each carbon and hydride of a ring of W ⁵ selected from the group consisting of cinnaolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl, other than the point of attachment The degree-containing nitrogen source is optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , provided that Q ^b is bonded to the lowest number of substituent positions of each W ⁵ , and (CH (R ³⁸ )) _r is bound to E ⁰ );

Y ⁰ is optionally Q ^b -Q ^ssssr (wherein Q ^ssssr is (CH (R ³⁸ )) _r -W ⁶ (r is an integer selected from 1 to 2, and W ⁶ is 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-benzofura Nilyl, 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, 2,7-imidazo (1,2-a) pyridinyl, 3,4-imidazo (1,2-a) pyridinyl, 3,5-imidazo (1,2-a ) Pyridinyl, 3,6-imidazo (1,2-a) pyridinyl, 3,7-imidazo (1,2-a) pyridinyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-iso Doryl, 1,5-isoindoleyl, 1,6-isoindoleyl, 2,4-isoindoleyl, 2,5-isoindoleyl, 2,6-isoindoleyl, 2,7-isoindoleyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzone company Zolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2 , 6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolin Nilyl, 2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl. 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-iso Quinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7.-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4 Each carbon of the W ⁶ ring other than the point of attachment selected from the group consisting of, 5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl; and The hydrido containing nitrogen source is optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , provided that Q ^b is bonded to the highest number of substituent positions of each W ⁶ , and (CH (R ³⁸ )) _r is bound to E ⁰ ).

In a preferred embodiment of the compound of formula (I) or a pharmaceutically acceptable salt thereof,

J ^a and J ^b are each O;

B is of formula V:

[Formula V]

Wherein D ¹ , D ² , J ¹ , J ² and K ¹ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, D ¹ , D ² At least one of J ¹ , J ² and K ¹ is O, at most one of D ¹ , D ² , J ¹ , J ² and K ¹ is S, and D ¹ , D ² , J ¹ , J ² and K ^If two of ¹ are O and S, one of D ¹ , D ² , J ¹ , J ^2, and K ¹ must be covalent, and no more than four of D ¹ , D ² , J ¹ , J ^2, and K ¹ Is N;

R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, Alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxyalkyl, hydroxy, amino, alkoxyamino, nitro, lower alkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl, alkylsulfonyl, Alkylsulfonylalkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, Alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy, carboxy, Consisting of carboxamido, carboxamidoalkyl and cyano Independently selected from the group;

R ¹⁶ , R ¹⁹ , R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently and independently Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b simultaneously and Q ^b is Q ^be ;

B is optionally hydrido, trialkylsilyl, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkylenyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl and C ₂ -C ₈ halo Selected from the group consisting of alkyl, wherein each member of group B is up to 6 from the point of attachment of B to A with one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ Optionally substituted at any carbon atom of;

B is optionally C₃-C₁₂Cycloalkyl and C₄-C₉Saturated heterocyclyl, wherein each ring carbon is R³³Ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo, provided that at least two ring carbons are not substituted at the same time with oxo and are adjacent to the carbon atom at the point of attachment Carbon and Nitrogen R⁹Or R¹³Optionally substituted with R⁹The ring carbon or nitrogen adjacent to the position and two atoms from the point of attachment is R¹⁰Optionally substituted with R¹³The ring carbon or nitrogen adjacent to the position and two atoms from the point of attachment is R¹²Replacement of rome and three from the point of attachment Atom Dropping R¹⁰Adjacent ring carbon or nitrogen is R¹¹Is optionally substituted with 3 atoms away from the point of attachment and R¹²Adjacent ring carbon or nitrogen is R³³Is optionally substituted with 4 atoms away from the point of attachment and R¹¹And R³³Adjacent ring carbon or nitrogen is R³⁴Optionally substituted with;

A is a single covalent bond, (W ⁷ ) _rr- (CH (R ¹⁵ )) _pa and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (where rr is an integer selected from 0 to 1, pa is an integer selected from 0 to 6, and W ⁷ is from the group consisting of 0, S, C (O), (R ⁷ ) NC (O), (R ⁷ ) NC (S) and N (R ⁷ ) And at least two of the group consisting of rr and pa cannot be 0 at the same time;

R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl;

R ¹⁵ is selected from the group consisting of hydrido, hydroxy, halo, alkyl and haloalkyl;

Ψ is selected from the group consisting of NH and NOH;

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl , Alkoxyamino, thiol and alkylthio;

R ² is Z ⁰ -Q;

Z ⁰ is a covalent single bond, (CR ⁴¹ R ⁴² ) _q (where q is an integer selected from 1 to 3), (CH (R ⁴¹ )) _g -W ^0- (CH (R ⁴² )) _p ( Wherein g and p are integers independently selected from 0 to 3, and W ⁰ is from the group consisting of 0, S, C (O), S (O), N (R ⁴¹ ) and ON (R ⁴¹ ) Selected) and (CH (R ⁴¹ )) _e -W ^22- (CH (R ⁴² )) _h (wherein e and h are integers independently selected from 0 to 1, and W ²² is CR ⁴¹ = CR ⁴² , 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl , 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 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-pyrrolidi , 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydro Selected from the group consisting of furanyl), provided that Z ⁰ is directly bonded to the uracil ring;

R ⁴¹ and R ⁴² are independently selected from the group consisting of amidino, hydroxyamino, hydrido, hydroxy, amino and alkyl;

Q is hydrido (Z ⁰ excluding covalent single bond), and is selected from the group consisting of Formula II:

[Formula II]

Wherein D ¹ , D ² , J ¹ , J ² and K ¹ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, D ¹ , D ² At least one of J ¹ , J ² and K ¹ is O, at most one of D ¹ , D ² , J ¹ , J ² and K ¹ is S, and D ¹ , D ² , J ¹ , J ² and K ^If two of ¹ are O and S, one of D ¹ , D ² , J ¹ , J ^2, and K ¹ must be covalent, and no more than four of D ¹ , D ² , J ¹ , J ^2, and K ¹ Is N, provided that R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen, ;

K is (CR ^4a R ^4b ) _n (wherein n is an integer selected from 1 to 2);

R ^4a and R ^4b are independently selected from the group consisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl and haloalkyl;

E ⁰ is E ¹ when K is (CR ^4a R ^4b ) _n , where E ¹ is a covalent single bond, C (O), C (S), C (O) N (R ⁷ ), (R ⁷ ) NC (O), S (O) ₂ , (R ⁷ ) NS (O) ₂ and S (O) ₂ N (R ⁷ );

Y ⁰ is formula IV:

[Formula IV]

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, K ² is C, D ⁵ At least one of D ⁶ , J ⁵ and J ⁶ is O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S, two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and If S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and up to four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N, provided that R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ represent hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, nitro, alkoxyamino, lower alkylamino, alkylthio, alkylsul Independently selected from the group consisting of finyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkylenylamino, haloalkoxyalkyl, carboalkoxy and cyano Become;

Q ^b is NR ²⁰ R ²¹ , aminoalkylenyl, Q ^be (wherein Q ^be is hydrido), N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) and C (NR ²⁵⁾ Is selected from the group consisting of NR ²³ R ²⁴ , provided that two R ²⁰ and R ²¹ are not hydroxy, amino, alkylamino or dialkylamino at the same time and two R ²³ and R ²⁴ are simultaneously hydroxy, amino, alkylamino Or not dialkylamino;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl, hydroxy, aminoalkylenyl, amino, dialkylamino, alkylamino and hydroxyalkyl Become;

Q ^s is a single covalent bond, (CR ³⁷ R ³⁸ ) _b (where b is an integer selected from 1 to 4) and (CH (R ¹⁴ )) _c -W ^1- (CH (R ¹⁵ )) _d ( Wherein c and d are integers independently selected from 1 to 3, and W ¹ is C (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O), S (O), S (O) ₂ , S (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) S (O) ₂ and N (R ¹⁴ ), provided that when bonded directly to N, R ¹⁴ is from other than halo. It is selected from the group consisting of (CR ³⁷ R ³⁸ ) _b and (CH (R ¹⁴ )) _c is bonded to E ⁰ ;

R ¹⁴ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl;

R ³⁷ and R ³⁸ are independently selected from the group consisting of hydrido, alkyl and haloalkyl;

R ³⁸ is optionally selected from the group consisting of aroyl and heteroaroyl;

Y ⁰ is optionally Q ^b -Q ^ss (where Q ^ss is optionally (CH (R ¹⁴ )) _e -W ^2- (CH (R ¹⁵ )) _h (where e and h are 1 Is an integer independently selected from 2, and W ² is CR ^4a = CR ^4b , provided that (CH (R ¹⁴ )) _e is bonded to E ⁰ );

Y ⁰ is Q ^b -Q ^ssss and Q ^b -Q ^ssssr (where Q ^ssss is (CH (R ³⁸ )) _r -W ⁵ and Q ^ssssr is (CH (R ³⁸ )) _r -W ⁶ (r Is an integer selected from 1 to 2, W ⁵ and W ⁶ are 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, 2,7-imidazo (1,2-a) pyridinyl, 3,4-imidazo (1,2-a) pyridinyl, 3,5-imidazo (1,2-a) pyridinyl, 3,6-imidazo (1,2-a) pyridinyl, 3,7-imidazo (1 , 2-a) pyridinyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl , 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindoleyl. Isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5 -Benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1 , 8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2 , 5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6 -Quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-qui Nolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3, 4-isoqui Linyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6 Isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3, Selected from the group consisting of 7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl and, the W ⁵ and one or more of the group consisting of rings, each of carbon and Hi give also contain a nitrogen source other than the attachment point of W ⁶ W ⁵ rings and W ⁶ of the by R ^9, R ^10, R ¹¹ and R ¹² Optionally substituted, provided that Q ^b is bonded to the lowest number of substituent positions in each W ⁵ and Q ^b is optionally bonded to the highest number of substituent positions in each W ⁶ and (CH (R ³⁸ )) _r is bonded to E ⁰ )).

In a more preferred embodiment of the compound of formula (I) or a pharmaceutically acceptable salt thereof,

J ^a and J ^b are each O;

B is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³² , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³⁶ , Carbon adjacent to R ³² and two atoms away from carbon at the point of attachment is optionally substituted with R ³³ , carbon adjacent to R ³⁶ and two atoms away from carbon at the point of attachment is optionally substituted with R ³⁵ , and R ³³ And any carbon adjacent to both R ³⁵ is optionally substituted with R ³⁴ ;

R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydride Roxy, amino, alkoxyamino, alkanoyl, haloalkanoyl, nitro, lower alkylamino, alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, amidosulfonyl , Monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, alkenylamino, carboalkoxy, carboxy, carboxamido, cyano And Q ^b is independently selected from the group consisting of;

B is optionally hydrido, trialkylsilyl, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkylenyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl and C ₂ -C ₈ halo Selected from the group consisting of alkyl, wherein each member of group B is up to 6 from the point of attachment of B to A with one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ Optionally substituted at any carbon atom of;

B is optionally C₃-C₁₂Cycloalkyl and C₄-C₉Saturated heterocyclyl, wherein each ring carbon is R³³Ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo, provided that at least two ring carbons are not substituted at the same time with oxo and are adjacent to the carbon atom at the point of attachment Carbon and Nitrogen R⁹Or R¹³Optionally substituted with R⁹The ring carbon or nitrogen adjacent to the position and two atoms from the point of attachment is R¹⁰Optionally substituted with R¹³The ring carbon or nitrogen adjacent to the position and two atoms from the point of attachment is R¹²Optionally substituted by 3 from the point of attachment Atom Dropping R¹⁰Adjacent ring carbon or nitrogen is R¹¹Is optionally substituted with 3 atoms away from the point of attachment and R¹²Adjacent ring carbon or nitrogen is R³³Is optionally substituted with 4 atoms away from the point of attachment and R¹¹And R³³Adjacent ring carbon or nitrogen is R³⁴Optionally substituted with;

R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy, halo Alkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, Independently selected from the group consisting of haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxyalkyl, carboxy, carboxamido and cyano;

A is a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1, pa is an integer selected from 0 to 3, and W ⁷ is 0 , S, C (O), (R ⁷ ) NC (O), (R ⁷ ) NC (S) and N (R ⁷ );

R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl;

R ¹⁵ is selected from the group consisting of hydrido, hydroxy, halo, alkyl and haloalkyl;

Ψ is NH;

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, Thiol and alkylthio;

R ² is Z ⁰ -Q;

Z ⁰ is a covalent single bond and (CR ⁴¹ R ⁴² ) _q (where q is an integer selected from 1 to 2), (CH (R ⁴¹ )) _g -W ^0- (CH (R ⁴² )) _p ( Wherein g and p are integers independently selected from 0 to 3, W ⁰ is selected from the group consisting of 0, S and N (R ⁴¹ )) and (CH (R ⁴¹ )) _e -W ^22- ( CH (R ⁴² )) _h (wherein e and h are integers independently selected from 0 to 1, W ²² is CR ⁴¹ = CR ⁴² , 1,2-cyclopropyl, 1,2-cyclobutyl, 1 , 2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl , 3,4-morpholinyl, 3,5-morpholinyl, 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-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydrofuranyl) Z ⁰ is directly bonded to the uracil ring;

R ⁴¹ and R ⁴² are independently selected from the group consisting of hydrido, hydroxy and amino;

Q is selected from the group consisting of hydrido, except Z ⁰ except covalent single bond, aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , The other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , and the carbon adjacent to R ⁹ and two atoms away from the carbon at the point of attachment is optionally substituted with R ¹⁰ and adjacent to R ¹³ and at the point of attachment Carbon two atoms away from carbon is optionally substituted with R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ;

K is CHR ^4a , wherein R ^4a is independently selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl and haloalkyl;

E ⁰ is selected from the group consisting of a covalent single bond, C (O) N (H), (H) NC (O), (R ⁷ ) NS (O) ₂ and S (O) ₂ N (R ⁷ ) ;

Y ⁰ is formula IV:

[Formula IV]

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, K ² is C, D ⁵ At least one of D ⁶ , J ⁵ and J ⁶ is O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S, two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and If S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and up to four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N, provided that R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl, Independently selected from the group consisting of alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano;

R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ;

Q ^b is NR ²⁰ R ²¹ , Q ^{be wherein} Q ^be is hydrido, N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) and C (NR ²⁵ ) NR ²³ R Selected from the group consisting of ²⁴ provided that two R ²⁰ and R ²¹ are not hydroxy, amino, alkylamino or dialkylamino at the same time, and two R ²³ and R ²⁴ are simultaneously hydroxy, amino, alkylamino or dialkylamino Not;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino;

Q ^s is a single covalent bond, (CR ³⁷ R ³⁸ ) _b (where b is an integer selected from 1 to 4) and (CH (R ¹⁴ )) _c -W ^1- (CH (R ¹⁵ )) _d ( Wherein c and d are integers independently selected from 1 to 3, and W ¹ is C (O) N (R ¹⁴ ), (R ¹⁴ ) NC (O), S (O), S (O) ₂ , S (O) ₂ N (R ¹⁴ ), N (R ¹⁴ ) S (O) ₂ and N (R ¹⁴ ), provided that when bonded directly to N, R ¹⁴ is from other than halo. It is selected from the group consisting of (CR ³⁷ R ³⁸ ) _b and (CH (R ¹⁴ )) _c is bonded to E ⁰ ;

R ¹⁴ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl;

R ³⁷ and R ³⁸ are independently selected from the group consisting of hydrido, alkyl and haloalkyl;

R ³⁸ is optionally selected from the group consisting of aroyl and heteroaroyl;

Y ⁰ is optionally Q ^b -Q ^ss (where Q ^ss is optionally (CH (R ¹⁴ )) _e -W ^2- (CH (R ¹⁵ )) _h (where e and h are 1 Is an integer independently selected from 2 to 2, W ² is CR ^4a = CH, provided that (CH (R ¹⁴ )) _e is bonded to E ⁰ ).

In an even more preferred embodiment of the compound of formula (I) or a pharmaceutically acceptable salt thereof,

J ^a and J ^b are each O;

B is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³² , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³⁶ , Carbon adjacent to R ³² and two atoms away from carbon at the point of attachment is optionally substituted with R ³³ , carbon adjacent to R ³⁶ and two atoms away from carbon at the point of attachment is optionally substituted with R ³⁵ , and R ³³ And any carbon adjacent to both R ³⁵ is optionally substituted with R ³⁴ ;

R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkyl Group consisting of thio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently from;

A is a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1, pa is an integer selected from 0 to 3, and W ⁷ is ( R ⁷ ) selected from the group consisting of NC (O) and N (R ⁷ );

R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl;

R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl;

Ψ is NH;

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of;

R ² is Z ⁰ -Q;

Z ⁰ is selected from the group consisting of covalent single bonds, 0, S, NH and CH ₂ ;

Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , Carbon adjacent to R ⁹ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹⁰ , carbon adjacent to R ¹³ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹² , R ¹⁰ And any carbon adjacent to both R ¹² is optionally substituted with R ¹¹ ;

R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, mono Independently selected from the group consisting of alkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano;

R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl Independently monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl and cyano;

K is CH ₂ ;

E ⁰ is C (O) N (H);

Y ⁰ is formula IV:

[Formula IV]

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, K ² is C, D ⁵ At least one of D ⁶ , J ⁵ and J ⁶ is optionally O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is optionally S, D ⁵ , D ⁶ , J ⁵ and J ^When two of ⁶ are O and S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and no more than four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N;

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano;

R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , Q ^be (Q ^be is hydrido) and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that both R ²⁰ and R ²¹ are hydroxy No two R ²³ and R ²⁴ are simultaneously hydroxy;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, alkyl and hydroxy;

Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ .

In another even more preferred embodiment of the compound of formula (I) or a pharmaceutically acceptable salt thereof,

J ^a and J ^b are each O;

B is optionally selected from the group consisting of hydrido, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl and C ₂ -C ₈ haloalkyl, wherein the B group Each member of is optionally substituted with up to 6 carbon atoms from any point of attachment of B to A with one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ ;

R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkyl Group consisting of thio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently from;

A is a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1, pa is an integer selected from 0 to 3, and W ⁷ is ( R ⁷ ) selected from the group consisting of NC (O) and N (R ⁷ );

R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl;

R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl;

Ψ is NH;

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of;

R ² is Z ⁰ -Q;

Z ⁰ is selected from the group consisting of covalent single bonds, 0, S, NH and CH ₂ ;

Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , Carbon adjacent to R ⁹ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹⁰ , carbon adjacent to R ¹³ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹² , R ¹⁰ And any carbon adjacent to both R ¹² is optionally substituted with R ¹¹ ;

R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, mono Independently selected from the group consisting of alkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano;

R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl Independently monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, alkenylamino, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl and cyano;

K is CH ₂ ;

E ⁰ is C (O) N (H);

Y ⁰ is formula IV:

[Formula IV]

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, K ² is C, D ⁵ At least one of D ⁶ , J ⁵ and J ⁶ is O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S, two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and If S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and up to four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N, provided that R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl , Alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkenylamino and cyano;

R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ;

Q ^b is NR ²⁰ R ²¹ , Q ^{be wherein} Q ^be is hydrido, C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ Is selected from the group consisting of: provided that two R ²⁰ and R ²¹ are not hydroxy at the same time and two R ²³ and R ²⁴ are not hydroxy at the same time;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl and hydroxy;

Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ .

In another even more preferred embodiment of the compound of formula (I) or a pharmaceutically acceptable salt thereof,

J ^a and J ^b are each O;

B is optionally C₃-C₇Cycloalkyl and C₄-C₆Saturated heterocyclyl, wherein each ring carbon is R³³Ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo, provided that at least two ring carbons are not substituted at the same time with oxo and are adjacent to the carbon atom at the point of attachment Carbon and Nitrogen R⁹Or R¹³Optionally substituted with R⁹The ring carbon or nitrogen adjacent to the position and two atoms from the point of attachment is R¹⁰Optionally substituted with R¹³The ring carbon or nitrogen adjacent to the position and two atoms from the point of attachment is R¹²Optionally substituted by 3 from the point of attachment Atom Dropping R¹⁰Adjacent ring carbon or nitrogen is R¹¹Is optionally substituted with 3 atoms away from the point of attachment and R¹²Adjacent ring carbon or nitrogen is R³³Is optionally substituted with 4 atoms away from the point of attachment and R¹¹And R³³Adjacent ring carbon or nitrogen is R³⁴Optionally substituted with;

R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, mono Independently selected from the group consisting of alkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano;

R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl Independently monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, alkenylamino, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl and cyano;

R ³³ and R ³⁴ represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkyl ami Independently selected from the group consisting of dosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b ;

A is a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1, pa is an integer selected from 0 to 3, and W ⁷ is ( R ⁷ ) selected from the group consisting of NC (O) and N (R ⁷ );

R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl;

R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl;

Ψ is NH;

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of;

R ² is Z ⁰ -Q;

Z ⁰ is selected from the group consisting of covalent single bonds, 0, S, NH and CH ₂ ;

Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , Carbon adjacent to R ⁹ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹⁰ , carbon adjacent to R ¹³ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹² , R ¹⁰ And any carbon adjacent to both R ¹² is optionally substituted with R ¹¹ ;

K is CH ₂ ;

E ⁰ is C (O) N (H);

Y ⁰ is formula IV:

[Formula IV]

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, K ² is C, D ⁵ At least one of D ⁶ , J ⁵ and J ⁶ is O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S, two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and If S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and up to four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N, provided that R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkenylamino and cyano;

R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , Q ^be (Q ^be is hydrido) and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that both R ²⁰ and R ²¹ are hydroxy No two R ²³ and R ²⁴ are simultaneously hydroxy;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl and hydroxy;

Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ .

In the most preferred embodiment of the compound of formula (I) or a pharmaceutically acceptable salt thereof

J ^a and J ^b are each O;

B is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³² , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³⁶ , Carbon adjacent to R ³² and two atoms away from carbon at the point of attachment is optionally substituted with R ³³ , carbon adjacent to R ³⁶ and two atoms away from carbon at the point of attachment is optionally substituted with R ³⁵ , and R ³³ And any carbon adjacent to both R ³⁵ is optionally substituted with R ³⁴ ;

R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkyl Group consisting of thio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently from;

A is a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1, pa is an integer selected from 0 to 3, and W ⁷ is N (R ⁷ );

R ⁷ is selected from the group consisting of hydrido and alkyl;

R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl;

Ψ is NH;

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of;

R ² is Z ⁰ -Q;

Z ⁰ is a covalent single bond;

Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , Carbon adjacent to R ⁹ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹⁰ , carbon adjacent to R ¹³ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹² , R ¹⁰ And any carbon adjacent to both R ¹² is optionally substituted with R ¹¹ ;

R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkyl amidosul Independently selected from the group consisting of fonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano;

R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino, alkylsulfonamido, Independently selected from the group consisting of amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido and cyano ;

K is CH ₂ ;

E ⁰ is C (O) N (H);

Y ⁰ is formula IV:

[Formula IV]

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, K ² is C, D ⁵ At least one of D ⁶ , J ⁵ and J ⁶ is O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S, two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and If S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and no more than four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N;

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano;

R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , Q ^{be wherein} Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and alkyl;

Q ^s is CH ₂ .

In another most preferred embodiment of the compound of formula (I) or a pharmaceutically acceptable salt thereof

J ^a and J ^b are each O;

B is optionally selected from the group consisting of hydrido, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl and C ₂ -C ₈ haloalkyl, wherein the B group Each member of is optionally substituted with up to 6 carbon atoms from any point of attachment of B to A with one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ ;

R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkyl Group consisting of thio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently from;

A is a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1, pa is an integer selected from 0 to 3, and W ⁷ is N (R ⁷ );

R ⁷ is selected from the group consisting of hydrido and alkyl;

R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl;

Ψ is NH;

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of;

R ² is Z ⁰ -Q;

Z ⁰ is a covalent single bond;

Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , Carbon adjacent to R ⁹ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹⁰ , carbon adjacent to R ¹³ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹² and R ¹⁰ And any carbon adjacent to both R ¹² is optionally substituted with R ¹¹ ;

R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkyl amidosul Independently selected from the group consisting of fonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano;

R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino, alkylsulfonamido, Independently selected from the group consisting of amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido and cyano ;

K is CH ₂ ;

E ⁰ is C (O) N (H);

Y ⁰ is formula IV:

[Formula IV]

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, K ² is C, D ⁵ At least one of D ⁶ , J ⁵ and J ⁶ is O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S, two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and If S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and up to four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N, provided that R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano;

R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ;

Q ^b is NR ²⁰ R ²¹ , Q ^{be wherein} Q ^be is hydrido, N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) and C (NR ²⁵ ) NR ²³ R ²⁴ is selected from the group consisting of;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido and alkyl;

Q ^s is CH ₂ .

In another most preferred embodiment of the compound of formula (I) or a pharmaceutically acceptable salt thereof

J ^a and J ^b are each O;

B is optionally C₃-C₇Cycloalkyl and C₄-C₆Saturated heterocyclyl, wherein each ring carbon is R³³Ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo, provided that at least two ring carbons are not substituted at the same time with oxo and are adjacent to the carbon atom at the point of attachment Carbon and Nitrogen R⁹Or R¹³Optionally substituted with R⁹The ring carbon or nitrogen adjacent to the position and two atoms from the point of attachment is R¹⁰Optionally substituted with R¹³The ring carbon or nitrogen adjacent to the position and two atoms from the point of attachment is R¹²Optionally substituted by 3 from the point of attachment Atom Dropping R¹⁰Adjacent ring carbon or nitrogen is R¹¹Is optionally substituted with 3 atoms away from the point of attachment and R¹²Adjacent ring carbon or nitrogen is R³³Is optionally substituted with 4 atoms away from the point of attachment and R¹¹And R³³Adjacent ring carbon or nitrogen is R³⁴Optionally substituted with;

R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkyl amidosul Independently selected from the group consisting of fonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano;

R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino, alkylsulfonamido, Independently selected from the group consisting of amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido and cyano ;

R ³³ and R ³⁴ are hydrido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, Independently selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido and cyano;

R ³³ is optionally Q ^b ;

A is a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1, pa is an integer selected from 0 to 3, and W ⁷ is N (R ⁷ );

R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl;

R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl;

Ψ is NH;

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of;

R ² is Z ⁰ -Q;

Z ⁰ is a covalent single bond;

Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , Carbon adjacent to R ⁹ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹⁰ , carbon adjacent to R ¹³ and two atoms away from carbon at the point of attachment is optionally substituted with R ¹² , R ¹⁰ And any carbon adjacent to both R ¹² is optionally substituted with R ¹¹ ;

K is CH ₂ ;

E ⁰ is C (O) N (H);

Y ⁰ is formula IV:

[Formula IV]

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and covalent bonds, at most one of which is covalent bond, K ² is C, D ⁵ At least one of D ⁶ , J ⁵ and J ⁶ is O, at most one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S, two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and If S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and up to four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N, provided that R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen;

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkenylamino and cyano;

R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , Q ^{be wherein} Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and alkyl;

Q ^s is CH ₂ .

In certain preferred embodiments of formula I, the compound has formula I-S or a pharmaceutically acceptable salt thereof:

[In the meal,

B is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4 -Pyrazolyl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4- Oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiazolyl, 5-isothiazolyl, 2- Oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidy Yl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2, From the group consisting of 4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,3-triazin-4-yl and 1,2,3-triazin-5-yl selected, and wherein one of the carbon adjacent to the carbon at the point of attachment is optionally substituted by R ^32, another carbon adjacent to the carbon at the point of attachment is optionally substituted with R ^36, R ³² and adjacent to Two atoms away from the carbon from the carbon at the point of attachment is optionally substituted with R ^33, adjacent to R ³⁶ and two atoms away from the carbon from the carbon at the point of attachment is optionally substituted by R ^35, in all of R ³³ and R ³⁵ Any adjacent carbon is optionally substituted with R ³⁴ ;

R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, amidino, guanidino, carboxy, methyl, ethyl, isopropyl, propyl, methoxy, ethoxy, isopropoxy, propoxy, Hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethyl Amino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-penta Fluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl , Acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2- Lifluoro-1-hydroxyethyl, 2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl , N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, cyano and Q ^b are independently selected from the group consisting of;

B is hydrido, trimethylsilyl, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl , Isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-part Tenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl 3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hex Cenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1 -Methyl-4-pentenyl, 1-ethyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1- Propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptinyl, 3-heptinyl, 4-heptinyl, 5-heptinyl, 2- Butyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-5-hexenyl. 1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1 -Ethyl-4-pentenyl, 1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 1-octyl, 2-octenyl, 3-octenyl, 4 -Octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 2-octinyl, 3-octinyl, 4-octinyl, 5-octinyl, 6-octinyl, 2-octyl, 1- Methyl-2-heptenyl, 1-methyl-3-heptenyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-hep Tinyl, 1-methyl-3-heptinyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptenyl, 1-methyl -3-heptinyl, 1-methyl-4-heptinyl, 1-methyl-5-heptinyl, 3-octyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl- 4-hexenyl, 1-ethyl-2-hexynyl, 1-ethyl-3-hexynyl, 1-ethyl-4-hexynyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-propyl-2-penty , 1-propyl-3-pentynyl, 1-butyl-2-butynyl, 1-butyl-3-butenyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl, 4- Trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl and 3,3,3-trifluoropropyl Selected from the group consisting of: wherein each circle of group B is any of up to 5 from the point of attachment of B to A with one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ Optionally substituted at a carbon atom of;

B is optionally cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaethan-2 -Yl, thiaethan-3-yl, cyclopentyl, cyclohexyl, adamantyl, norbornyl, 3-trifluoromethylnorbornyl, 7-oxabicyclo [2.2.l] heptan-2-yl, Bicyclo [3.1.0] hexane-6-yl, cycloheptyl, cyclooctyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1 -Piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 4H-2 -Pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3 From the group consisting of tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl and 3-tetrahydrothienyl Selected, and wherein each ring carbon is optionally substituted with R ^33, 2 a ring carbon or nitrogen adjacent to the carbon atom is optionally substituted with R ⁹ or R ^13, adjacent to the R ⁹ position and from the point of attachment at an attachment point one Ring carbon or nitrogen which is atom-atom is optionally substituted with R ^10, and ring carbon or nitrogen which is adjacent to R ¹³ and two atoms away from the point of attachment is optionally substituted with R ¹² ;

R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, isopropyl, propyl, methoxy, ethoxy, isopropoxy, Propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3, 3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1-hydrate Cyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, 2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl Independently methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and cyano;

A is a single covalent bond, 0, S, NH, N (CH ₃ ), N (OH), C (O), CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), N (CH ₃ ) C (O), C (O) NH, C (O) N (CH ₃ ), CF ₃ CC (O), C (O) CCH ₃ , C (O) CCF ₃ , CH ₂ C (O), (O ) CCH ₂ , CH ₂ CH ₂ , CH ₂ CH ₂ CH ₂ , CH ₃ CHCH ₂ , CF ₃ CHCH ₂ , CH ₃ CC (O) CH ₂ , CF ₃ CC (O) CH ₂ , CH ₂ C (O) CCH ₃ , CH ₂ C (O) CCF ₃ , CH ₂ CH ₂ C (O) and CH ₂ (O) CCH ₂ ;

A is optionally selected from the group consisting of CH ₂ N (CH ₃ ), CH ₂ N (CH ₂ CH ₃ ), CH ₂ CH ₂ N (CH ₃ ) and CH ₂ CH ₂ N (CH ₂ CH ₃ ) With the proviso that B is hydrido;

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, hydroxy, amino, thiol, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, isopropyl, Propyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, methoxy, ethoxy, propoxy, hydroxymethyl , 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, ethoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro And bromo;

R ² is Z ⁰ -Q;

Z ⁰ is a covalent single bond, 0, S, NH, CH ₂ , CH ₂ CH ₂ , CH (OH), CH (NH ₂ ), CH ₂ CH (OH), CH ₂ CHNH ₂ , CH (OH) CH ₂ And CH (NH ₂ ) CH ₂ ;

Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4 -Pyrazolyl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4- Oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiazolyl, 5-isothiazolyl, 2- Oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidy Yl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2, From the group consisting of 4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,3-triazin-4-yl and 1,2,3-triazin-5-yl Wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ and adjacent to R ⁹ Two atoms away from the carbon from the carbon at the point of attachment is optionally substituted with R ^10, adjacent to R ¹³ and two atoms away from the carbon from the carbon at the point of attachment is optionally substituted by R ^12, in all of R ¹⁰ and R ¹² Any adjacent carbon is optionally substituted with R ¹¹ ;

K is CHR ^4a (wherein R ^4a is methyl, ethyl, propyl, isopropyl, hydroxymethyl, 1-hydroxyethyl, methoxymethyl, trifluoromethyl, pentafluoroethyl, 2,2,2- Independently selected from the group consisting of trifluoromethyl, methylthiomethyl and hydrido);

E ⁰ is selected from the group consisting of covalent single bonds, C (O) N (H), (H) NC (O) and S (O) ₂ NH;

Y ⁰ is selected from the group of the formula consisting of:

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, isopropyl, propyl, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, Amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, NN-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl Thio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, fluoromethyl, perfluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoro Ropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, Acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro 1-hydroxyethyl, and cyano are independently selected from the group consisting of;

R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ;

Q ^b is NR ²⁰ R ²¹ , Q ^{be wherein} Q ^be is hydrido, C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ Is selected from the group consisting of: provided that two R ²⁰ and R ²¹ are not simultaneously hydroxy, N-methylamino and N, N-dimethylamino, and two R ²³ and R ²⁴ are simultaneously hydroxy, N-methylamino and Not N, N-dimethylamino;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are hydrido, methyl, ethyl, propyl, butyl, isopropyl, hydroxy, 2-aminoethyl, 2- (N-methylamino) ethyl And 2- (N, N-dimethylamino) ethyl;

Q ^s is a single covalent bond, CH ₂ , CH ₂ CH ₂ , CH ₃ CH, CF ₃ CH, CH ₃ CHCH ₂ , CF ₃ CHCH ₂ , CH ₂ (CH ₃ ) CH, CH = CH, CF = CH, C (CH ₃ ) = CH, CH = CHCH ₂ , CF = CHCH ₂ , C (CH ₃ ) = CHCH ₂ , CH ₂ CH = CH, CH ₂ CF = CH, CH ₂ C (CH ₃ ) = CH, CH ₂ CH = CHCH ₂ , CH ₂ CF = CHCH ₂ , CH ₂ C (CH ₃ ) = CHCH ₂ , CHCH = CHCH ₂ CH ₂ , CH ₂ CF = CHCHCH and CH ₂ C (CH ₃ ) = CHCH ₂ CH ₂ Selected from the group.

In a more preferred specific embodiment of formula I, the compound has formula I-MPS wherein B is aromatic or a pharmaceutically acceptable salt thereof:

In a more preferred specific embodiment of formula I, the compound has formula I-MPS or a pharmaceutically acceptable salt thereof, wherein B is aromatic:

(I-MPS where B is aromatic)

Wherein B is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3- Pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl , 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl and 1,3,5-triazin-2-yl, wherein the carbon at the point of attachment adjacent one carbon is substituted with R ^32, and another carbon adjacent to the carbon of attachment points is optionally substituted by R ^36, dropping the two atoms from the carbon of attachment point on the carbon adjacent to R ³² is optionally substituted with R ^33, attached to dropping two atoms from the point of the carbon-carbon adjacent to R ³⁶ is optionally substituted by R ^35, any carbon adjacent to both R ³³ and R ³⁵ is optionally substituted with R ^34;

R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, Ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2, 2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo , Amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxy independent of the hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amido carbonyl, N- methyl amido-carbonyl, N, N- dimethyl-amido-carbonyl, cyano, and the group consisting of Q ^b Is selected;

A is a single covalent bond, NH, N (CH ₃ ), N (OH), CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), N (CH ₃ ) C (O), C (O) NH , C (O) N (CH ₃ ), CH ₂ CH ₂ , CH ₂ CH ₂ CH ₂ , CH ₃ CHCH ₂ and CF ₃ CHCH ₂ ;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that both R ²⁰ and R ²¹ are hydroxy No two R ²³ and R ²⁴ are simultaneously hydroxy);

R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl and hydroxy;

Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ ).

In another more preferred specific embodiment of Formula (I), the compound has Formula (I-MPS) or a pharmaceutically acceptable salt thereof, wherein B is a non-cyclic substituent:

[Formula I-MPS]

(I-MPS, where B is a non-cyclic substituent)

Wherein B is hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert- Butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2- Butenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2- Methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3- Hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1 -Propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptinyl , 3-heptinyl, 4-heptinyl, 5-heptinyl, 2-heptyl, 1- Tyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-5-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexyl Neyl, 1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl , 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5, 5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein Each circle of group B is optionally substituted with one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ at any up to 5 carbon atoms from the point of attachment of B to A;

R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, Ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2, 2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo , Amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxy independent of the hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amido carbonyl, N- methyl amido-carbonyl, N, N- dimethyl-amido-carbonyl, cyano, and the group consisting of Q ^b Is selected;

A is a single covalent bond, NH, N (CH ₃ ), N (OH), CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), N (CH ₃ ) C (O), C (O) NH , C (O) N (CH ₃ ), CH ₂ CH ₂ , CH ₂ CH ₂ CH ₂ , CH ₃ CHCH ₂ and CF ₃ CHCH ₂ ;

A is optionally selected from the group consisting of CH ₂ N (CH ₃ ), CH ₂ N (CH ₂ CH ₃ ), CH ₂ CH ₂ N (CH ₃ ) and CH ₂ CH ₂ N (CH ₂ CH ₃ ) With the proviso that B is hydrido;

Q ^b is NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido, C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) Selected from the group consisting of: provided that two R ²⁰ and R ²¹ are not hydroxy at the same time and two R ²³ and R ²⁴ are not hydroxy at the same time;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl and hydroxy;

Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ ).

In another more preferred embodiment of Formula I, the compound has Formula I-MPS or a pharmaceutically acceptable salt thereof, wherein B is a non-aromatic cyclic substituent:

[Formula I-MPS]

(I-MPS, where B is a non-aromatic cyclic substituent)

Wherein B is optionally cyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaethan-3-yl, Cyclopentyl, cyclohexyl, norbornyl, 7-oxabicyclo [2.2.1] heptan-2-yl, bicyclo [3.1.0] hexane-6-yl, cycloheptyl, 2-morpholinyl, 3- Morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrroli Diyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2 -Yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydro thienyl, and 3-tetrahydro-thienyl is selected from the group consisting of carbonyl, in which each ring carbon is optionally substituted with R ^33, the carbon of attachment points Ring carbons and a nitrogen adjacent to the character is R ⁹ or optionally substituted with R ^13, dropping the two atoms from the point of attachment R ring carbon or nitrogen adjacent to the ^9-position is optionally substituted with R ^10, dropping the two atoms from the point of attachment on R ¹³ Adjacent ring carbon or nitrogen is optionally substituted with R ¹² ;

A is a single covalent bond, NH, N (CH ₃ ), N (OH), CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), N (CH ₃ ) C (O), C (O) NH , C (O) N (CH ₃ ), CH ₂ CH ₂ , CH ₂ CH ₂ CH ₂ , CH ₃ CHCH ₂ and CF ₃ CHCH ₂ ;

R ³³ represents hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacet Amido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2 , 3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl Independently, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, cyano and Q ^b ;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that both R ²⁰ and R ²¹ are hydroxy No two R ²³ and R ²⁴ are simultaneously hydroxy;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl and hydroxy;

Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ ).

More preferred specific embodiment (I-MPS) compounds of the present invention having the formula: or pharmaceutically acceptable salts thereof have common structural units:

(In the meal,

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2 , 2-tetrafluoroethoxy, fluoro, chloro and bromo;

R ² is Z ⁰ -Q;

Z ⁰ is selected from the group consisting of covalent single bonds, O, S, NH and CH ₂ ;

Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4 -Pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyri Midinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl and 1,3,5-triazin-2-yl, wherein one carbon adjacent the carbon at the point of attachment Or nitrogen is optionally substituted with R ⁹ , another carbon or nitrogen adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , two atoms away from carbon at the point of attachment and carbon or nitrogen adjacent to R ⁹ is optionally substituted with R ¹⁰ , Two atoms away from the carbon at the point of attachment, the carbon adjacent to R ¹³ is optionally substituted with R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ;

R ⁹ , R ¹¹ and R ¹³ are hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N -Methylamino, N, N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2 , 3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N- Methyl amidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl , N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and cyano are independently selected from the group consisting of;

R ¹⁰ and R ¹² represent hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, meth Methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amido Dosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl Independently selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro, chloro, bromo and cyano Become;

Y ⁰ is selected from the group of formula consisting of:

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, Amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsul Finyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy , 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydride Independently selected from the group consisting of hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl and cyano;

R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ).

In a most preferred specific embodiment of formula I, the compound has formula I-EMPS or a pharmaceutically acceptable salt thereof, wherein B is aromatic:

(I-EMPS where B is aromatic)

Wherein B is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3- Selected from the group consisting of pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl and 5-isoxazolyl, one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³² , the point of attachment of, and the other carbon adjacent to the carbon is optionally the R ³⁶ substituted, dropping two atoms from the carbon of the point of attachment is optionally substituted by R ³² carbon is R ³³ is adjacent to, falling two atoms from the carbon of attachment point on the carbon adjacent to R ³⁶ are R Optionally substituted with ³⁵ and any carbon adjacent to both R ³³ and R ³⁵ is optionally substituted with R ³⁴ ;

R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methyl Thio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amido Independently selected from the group consisting of docarbonyl, carboxy, cyano and Q ^b ;

A is selected from the group consisting of a single covalent bond, NH, N (CH ₃ ), CH ₂ , CH ₃ CH and CH ₂ CH ₂ ;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that the Q ^b group is directly bonded to a carbon atom;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, methyl and ethyl;

Q ^s is CH ₂ ).

In another most preferred embodiment of formula I, the compound has formula I-EMPS or a pharmaceutically acceptable salt thereof, wherein B is a non-cyclic substituent:

[Formula I-EMPS]

(I-EMPS, where B is a non-cyclic substituent)

Wherein B is hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-part Tenyl, 3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2- Butenyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptinyl, 3-heptinyl, 4-heptinyl, 5-heptinyl, 2-heptyl , 1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl- 4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2 -Trifluoroethyl, 2,2-difluoropropyl, 4-triflu Romethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl and 3,3,3-trifluoropropyl Wherein each circle of the group B is one of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ at any up to 5 carbon atoms from the point of attachment of B to A Optionally substituted as above;

R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methyl Thio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amido Independently selected from the group consisting of docarbonyl, carboxy, cyano and Q ^b ;

A is selected from the group consisting of a single covalent bond, NH, N (CH ₃ ), CH ₂ , CH ₃ CH and CH ₂ CH ₂ ;

A is optionally selected from the group consisting of CH ₂ N (CH ₃ ), CH ₂ N (CH ₂ CH ₃ ), CH ₂ CH ₂ N (CH ₃ ) and CH ₂ CH ₂ N (CH ₂ CH ₃ ) With the proviso that B is hydrido;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ), provided that the Q ^b group is carbon Is directly bonded to an atom;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, methyl and ethyl;

Q ^s is CH ₂ ).

In another most preferred specific embodiment of formula I, the compound has formula I-EMPS or a pharmaceutically acceptable salt thereof, wherein B is a non-aromatic cyclic substituent:

[Formula I-EMPS]

(I-EMPS, where B is a non-aromatic cyclic substituent)

Wherein B is optionally cyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-3-yl, thiaethan-3-yl, cyclopentyl, cyclohexyl, 1-pyrrolidinyl, 2- Pyrrolidinyl, 3-pyrrolidinyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl and 3-tetrahydrothienyl, wherein each ring carbon is R is optionally substituted with ^33, ring carbons and a nitrogen adjacent to the carbon of attachment points being optionally substituted with R ⁹ or R ^13, dropping the two atoms from the point of attachment ring carbon or nitrogen adjacent to the R ⁹ position is optionally substituted by R ^10, A ring carbon or nitrogen two atoms away from the point of attachment and adjacent to the R ¹³ position is optionally substituted with R ¹² ;

R ³³ represents hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, carboxy, amino, N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethyl, Pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, cyano and Q ^b Independently selected from the group consisting of;

A is selected from the group consisting of a single covalent bond, NH, N (CH ₃ ), CH ₂ , CH ₃ CH and CH ₂ CH ₂ ;

Q ^b is selected from the group consisting of NR ²⁰ R ²¹ and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that the Q ^b group is bonded directly to a carbon atom;

R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, methyl and ethyl;

Q ^s is CH ₂ ).

Most preferred specific embodiment (I-EMPS) compounds of the present invention having the formula: or pharmaceutically acceptable salts thereof have common structural units:

(In the meal,

M is selected from the group consisting of N and R ¹ -C;

R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylamino, methyl Thio, trifluoromethoxy, fluoro and chloro;

R ² is Z ⁰ -Q;

Z ⁰ is a covalent single bond;

Q is selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl and 3-pyridyl Where one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ⁹ is Optionally substituted with R ¹⁰ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ¹³ is optionally substituted with R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ;

R ⁹ , R ¹¹ and R ¹³ are hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N, N-dimethylamino, methylthio, trifluoromethyl, pentafluoro Roethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxy Independently selected from the group consisting of ethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy and cyano;

R ¹⁰ and R ¹² represent hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxy Hydroxyethyl, 2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl Independently selected from the group consisting of, N-methylamino, dimethylamino, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo and cyano Become;

Y ⁰ is selected from the group of formula consisting of:

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N- Methylamino, dimethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluorome Independently selected from the group consisting of methoxy, fluoro, chloro, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, carboxy and cyano).

The compounds of the present invention can be used in anticoagulant therapy for the treatment and prevention of various thrombotic symptoms including coronary and cerebrovascular diseases. The compounds of the present invention can be used to inhibit serine proteases and factors II, VI, VI, IV, VI, VI or VI associated with a coagulation cascade. The compounds of the present invention can inhibit platelet aggregate formation, fibrin formation, thrombus formation and embolism formation in mammals, blood, blood products and mammalian organs. In addition, the compounds may be used in mammals with unstable angina, refractory angina, myocardial infarction, transient ischemic attack, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, intraocular fibrin accumulation, and re It can be used to treat or prevent reclosure or restenosis of communicating blood vessels. In addition, the compounds may be used for prophylactic treatment of subjects at risk of developing such diseases. The compound can be used to lower the risk of atherosclerosis. The compounds of formula I will also be used for the prevention of cerebrovascular accidents (CVAs) or strokes.

These compounds are not only useful for treating humans, but also for veterinary treatment of farm animals, exotic animals, and companion animals, including mammals, rodents, and the like. More preferred animals include horses, dogs, and cats.

In another embodiment of the invention, the novel compounds are selected from the compounds listed in Examples 1-7 below.

For clarity, the use of generic terms in the description of compounds is defined herein.

Standard single character element symbols are used to represent atoms of a particular type unless otherwise indicated. The symbol "C" represents a carbon atom. The symbol "O" represents an oxygen atom. The symbol "N" represents a nitrogen atom. The symbol "P" represents a phosphorus atom. The symbol "S" represents a sulfur atom. The symbol "H" represents a hydrido atom. The double letter element symbol is used to define the elements of the periodic table (ie Cl stands for chlorine, Se stands for selenium, etc.).

As used herein, the term "alkyl", alone or in other terms such as "haloalkyl" and "alkylthio", has from 1 to about 10, preferably from 3 to about 8, more preferably Preferably an acyclic alkyl radical that is 3 to about 6. The alkyl radical may be optionally substituted with groups as defined below. Examples of such radicals are methyl, ethyl, chloroethyl, hydroxyethyl, n-propyl, oxopropyl, isopropyl, n-butyl, cyanobutyl, isobutyl, sec-butyl, tert-butyl, pentyl, aminopentyl, Iso-amyl, hexyl, octyl and the like.

The term "alkenyl" refers to an unsaturated, acyclic hydrocarbon radical comprising at least one double bond therein. Such alkenyl radicals have about 2 to about 10 carbon atoms, preferably about 3 to about 8 carbon atoms, more preferably 3 to about 6 carbon atoms. The alkenyl radicals may be optionally substituted with groups as defined below. Examples of suitable alkenyl radicals are propenyl, 2-chloropropenyl, buten-1-yl, isobutenyl, penten-1-yl, 2-methylbuten-1-yl, 3-methylbuten-1-yl, hexene -1-yl, 3-hydroxyhexen-1-yl, hepten-1-yl, octen-1-yl and the like.

The term “alkynyl” is an unsaturated, non-cyclic hydrocarbon radical comprising at least one triple bond therein, wherein the carbon number is from about 2 to about 10, preferably from about 3 to about 8, more preferably from 3 to about 6 It means phosphorus radicals. The alkynyl radical may be optionally substituted with groups as defined below. Examples of suitable alkynyl radicals are ethynyl, propynyl, hydroxypropynyl, butyn-1-yl, butyn-2-yl, fentin-1-yl, pentyn-2-yl, 4-methoxypentin-2- 1, 3-methylbutyn-1-yl, hexyn-1-yl, hexyn-2-yl, hexyn-3-yl, 3,3-dimethylbutyn-1-yl radicals and the like.

The term "hydrido" refers to a single hydrogen atom (H). This hydrido radical may, for example, attach to an oxygen atom to form a "hydroxy" radical, and one hydrido radical may attach to a carbon atom to form a "methine" radical -CH =, Two hydrido radicals may be attached to a carbon atom to form a "methylene" (-CH _2- ) radical.

The term "carbon" radical refers to a carbon atom without any covalent bonds, capable of forming four covalent bonds.

The term "cyano" radical refers to a carbon radical in which three of the four covalent bonds share one nitrogen atom.

The term "hydroxyalkyl" means a radical in which any one or more alkyl carbon atoms are substituted with hydroxyl as defined above. Specifically included are monohydroxyalkyl, dihydroxyalkyl and polyhydroxyalkyl radicals.

The term "alkanoyl" means a radical in which one or more terminal alkyl carbon atoms are replaced with one or more carbonyl radicals as defined below. Specifically included are monocarbonylalkyl and dicarbonylalkyl radicals. Examples of monocarbonylalkyl radicals include formyl, acetyl and pentanoyl. Examples of dicarbonylalkyl radicals include oxalyl, malonyl and succinyl.

The term "alkylene" radical refers to a linear or branched radical having 1 to about 10 carbon atoms and having an attachment point for two or more covalent bonds. Examples of such radicals are methylene, ethylene, methylethylene and isopropylidene.

The term "alkenylene" radical refers to a linear or branched radical having 2 to about 10 carbon atoms, having at least one double bond, and having an attachment point for at least two covalent bonds. Examples of such radicals are 1,1-vinylidene (CH ₂ = C), 1,2-vinylidene (-CH = CH-) and 1,4-butadienyl (-CH = CH-CH = CH-) There is this.

The term "halo" means a halogen such as a fluorine, chlorine, bromine or iodine atom.

The term "haloalkyl" means a radical in which any one or more alkyl carbon atoms are substituted with halo as defined above. Specifically included are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. For example, monohaloalkylradicals may have one of the bromo, chloro or fluoro atoms in the radical. Dihalo radicals may have two or more of the same halo atoms or a combination of different halo radicals, and polyhaloalkyl radicals may have more than two of the same halo atoms or a combination of different halo radicals. More preferred haloalkyl radicals are "lower haloalkyl" radicals having 1 to about 6 carbon atoms. Examples of such haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trifluoroethyl, pentafluoroethyl, heptafluoropropyl, difluorochloro Methyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl.

The term "hydroxyhaloalkyl" means a radical wherein any one or more haloalkyl carbon atoms are substituted with hydroxy as defined above. Examples of “hydroxyhaloalkyl” radicals include hexafluorohydroxypropyl.

The term "haloalkylene radical" refers to an alkylene radical wherein any one or more alkylene carbon atoms are substituted with halo as defined above. Dihalo alkylene radicals may have two or more of the same halo atoms or a combination of different halo radicals, and polyhaloalkylene radicals may have more than two of the same halo atoms or a combination of different halo radicals. More preferred haloalkylene radicals are "lower haloalkylene" radicals having 1 to about 6 carbon atoms. Examples of "haloalkylene" radicals include difluoromethylene, tetrafluoroethylene, tetrachloroethylene, alkyl substituted monofluoromethylene and aryl substituted trifluoromethylene.

The term "haloalkenyl" refers to a linear or branched radical having 1 to about 10 carbon atoms and having at least one double bond, wherein any one or more alkenyl carbon atoms are substituted with halo as defined above. Dihaloalkenyl radicals can have two or more of the same halo atoms or a combination of different halo radicals, and polyhaloalkenyl radicals can have more than two of the same halo atoms or a combination of different halo radicals.

The terms "alkoxy" and "alkoxyalkyl" refer to linear or branched oxy containing radicals having alkyl moieties each having 1 to about 10 carbon atoms, such as methoxy radicals. The term "alkoxyalkyl" also refers to alkyl radicals in which at least one alkoxy radical is attached to an alkyl radical, that is to say a monoalkoxyalkyl and dialkoxyalkyl radical. More preferred alkoxy radicals are "lower alkoxy" radicals having 1 to 6 carbon atoms. Examples of such radicals include methoxy, ethoxy, propoxy, butoxy, isopropoxy and tert-butoxy alkyl. "Alkoxy" radicals may be further substituted with one or more halo atoms such as fluoro, chloro or bromo to provide "haloalkoxy" and "haloalkoxyalkyl" radicals. Examples of the haloalkoxy radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy, difluoromethoxy, trifluoroethoxy, fluoroethoxy, tetrafluoroethoxy, pentafluoroethoxy and fluoro Propoxy. Examples of such haloalkoxyalkyl radicals include fluoromethoxymethyl, chloromethoxyethyl, trifluoromethoxymethyl, difluoromethoxyethyl and trifluoroethoxymethyl.

The terms "alkenyloxy" and "alkenyloxyalkyl" refer to linear or branched oxy containing radicals having alkenyl moieties having 2 to about 10 carbon atoms each, such as ethenyloxy or propenyloxy radicals. The term "alkenyloxyalkyl" also refers to alkenyl radicals in which one or more alkenyloxy radicals are attached to an alkyl radical, that is to say a monoalkenyloxyalkyl and a dialkyloxyalkyl radical. More preferred alkenyloxy radicals are "lower alkenyloxy" radicals having 2 to 6 carbon atoms. Examples of such radicals include ethenyloxy, propenyloxy, butenyloxy and isopropenyloxy alkyl. An "alkenyloxy" radical may be further substituted with one or more halo atoms such as fluoro, chloro or bromo to provide a "haloalkenyloxy" radical. Examples of such radicals include trifluoroethenyloxy, fluoroethenyloxy, difluoroethenyloxy and fluoropropenyloxy.

The term "haloalkoxyalkyl" also means an alkyl radical wherein at least one haloalkoxy radical is attached to an alkyl radical, that is to say an alkyl radical which forms a monohaloalkoxyalkyl and a dihaloalkoxyalkyl radical. The term "haloalkenyloxy" also refers to an oxygen radical wherein at least one haloalkenyloxy radical is attached to an oxygen radical, that is to say a monohaloalkenyloxy and dihaloalkenyloxy radical. Further, the term "haloalkenyloxyalkyl" means an alkyl radical wherein at least one haloalkenyloxy radical is attached to an alkyl radical, that is to say an alkyl radical which forms a monohaloalkenyloxyalkyl and a dihaloalkenyloxyalkyl radical. do.

The term "alkylenedioxy" radical refers to an alkylene radical in which two or more oxygens are bonded to a single alkylene group. Examples of "alkylenedioxy" radicals include methylenedioxy, ethylenedioxy, alkyl substituted methylenedioxy and aryl substituted methylenedioxy. The term "haloalkylenedioxy" radical refers to a haloalkylene radical in which two or more oxy groups are bonded to a single haloalkyl group. Examples of “haloalkylenedioxy” radicals include difluoromethylenedioxy, tetrafluoroethylenedioxy, tetrachloroethylenedioxy, alkyl substituted monofluoromethylenedioxy and aryl substituted monofluoromethylenedioxy. Included.

The term "aryl", used alone or in combination, is a carbocyclic aromatic system comprising one, two or three rings, meaning that the rings can be attached or fused together in a pendant manner. do. The term "fusion" means that the second ring is present (ie attached or formed) by having two adjacent atoms in common (ie, shared) with the first ring. The term "fusion" is equivalent to the term "condensation". The term "aryl" refers to aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl.

The term "perhaloaryl" refers to an aromatic radical such as phenyl, naphthyl, tetrahydronaphthyl, indan and biphenyl, in which the aryl radical is substituted with three or more halo radicals as defined below.

The term “heterocyclyl” includes saturated and partially saturated heteroatoms having 4 to 15 ring members selected from carbon, nitrogen, sulfur and oxygen, referred to herein as “C _{4 to} C ₁₅ heterocyclyl”. By cyclic radical, it is meant that at least one ring atom is a heteroatom. Heterocyclyl radicals may include one, two or three rings that may be attached or fused in a pendant manner. Examples of saturated heterocyclic radicals include saturated 3-6 membered heteromonocyclic groups having 1 to 4 nitrogen atoms (eg, pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, and the like); Saturated 3-6 membered heteromonocyclic groups having 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [eg, morpholinyl, etc.]; Saturated 3 to 6 membered heteromocyclic groups (eg, thiazolidinyl, etc.) having 1 to 2 sulfur and 1 to 3 nitrogen atoms are included. Examples of partially saturated heterocyclyl radicals include dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole. Non-limiting examples of heterocyclic radicals include 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidinyl, 1,3-dioxolanyl, 2H-pyranyl, 4H-pyranyl, piperidinyl, 1,4 Dioxanyl, morpholinyl, 1,4-ditianyl, thiomorpholinyl and the like.

The term “heteroaryl” is a fully unsaturated heteroatom containing cyclic aromatic radical having 5 to 15 ring members selected from carbon, nitrogen, sulfur and oxygen, meaning that at least one ring atom is a heteroatom. Heteroaryl radicals may include one, two or three rings that may be attached or fused in a pendant manner. Examples of “heteroaryl” radicals include: unsaturated 5-6 membered heteromonocyclyl groups having 1 to 4 nitrogen atoms, such as pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, 2-pyridyl , 3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl [eg 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H- 1,2,3-triazolyl and the like], tetrazolyl [eg, 1H-tetrazolyl, 2H-tetrazolyl and the like] and the like; Unsaturated condensed heterocyclic groups having 1 to 5 nitrogen atoms, for example indolyl, isoindoleyl, indolinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyrida Genyl [eg, tetrazolo [1,5-b] pyridazinyl, etc.]; Unsaturated 3-6 membered heteromonocyclic groups containing oxygen atoms such as pyranyl, 2-furyl, 3-furyl and the like; Unsaturated 5-6 membered heteromonocyclic groups containing a sulfur atom such as 2-thienyl, 3-thienyl and the like; Unsaturated 5-6 membered heteromonocyclic groups having 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms such as oxazolyl, isoxazolyl, oxadiazolyl [e.g. 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl and the like]; Unsaturated condensed heterocyclic groups having 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [eg, benzoxazolyl, benzoxadiazolyl and the like]; Unsaturated 5-6 membered heteromonocyclic groups having 1 to 2 sulfur and 1 to 3 nitrogen, such as thiazolyl, thiadiazolyl [eg 1,2,4-thiadiazolyl, 1,3,4 -Thiadiazolyl, 1,2,5-thiadiazolyl and the like]; Unsaturated condensed heterocyclic groups having 1 to 2 sulfur and 1 to 3 nitrogen, such as benzothiazolyl, benzothiadiazolyl and the like. The term also refers to radicals in which heterocyclic radicals are fused with aryl radicals. Examples of such fused bicyclic radicals include benzofuran, benzothiophene and the like. The "heterocyclyl" group may have 1 to 3 substituents as defined below. Preferred heterocyclic radicals include 5-12 membered fused or unfused radicals. Non-limiting examples of heteroaryl radicals include pyrrolyl, pyridinyl, pyridyloxy, pyrazolyl, triazolyl, pyrimidinyl, pyridazinyl, oxazolyl, thiazolyl, imidazolyl, indolyl, thiophenyl, furanyl , Tetrazolyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,3- Triazolyl, 1,3,4-thiadiazolyl, pyrazinyl, piperazinyl, 1,3,5-triazinyl, 1,3,5-tritianyl, benzo (b) thiophenyl, benzimidazolyl , Quinolinyl, tetraazolyl and the like.

The term "sulfonyl", each used alone or in connection with another term such as alkylsulfonyl, refers to a _divalent radical -SO _2- , respectively. "Alkylsulfonyl" means an alkyl radical attached to a sulfonyl radical, wherein alkyl is as defined above. "Alkylsulfonylalkyl" means an alkylsulfonyl radical attached to an alkyl radical, wherein alkyl is as defined above. "Haloalkylsulfonyl" means a haloalkyl radical attached to a sulfonyl radical, where haloalkyl is as defined above. "Haloalkylsulfonylalkyl" means a haloalkylsulfonyl radical, where alkyl is as defined above, attached to an alkyl radical. The term "aminosulfonyl" refers to an amino radical attached to a sulfonyl radical.

The term "sulfinyl", when used alone or in connection with other terms such as alkylsulfinyl, refers to a divalent radical -S (O)-, respectively. "Alkylsulfinyl" means an alkyl radical attached to a sulfinyl radical, wherein alkyl is as defined above. "Alkylsulfinylalkyl" means an alkylsulfinyl radical attached to an alkyl radical, wherein alkyl is as defined above. "Haloalkylsulfinyl" means a haloalkyl radical attached to a sulfinyl radical, where haloalkyl is as defined above. "Haloalkylsulfinylalkyl" means a haloalkylsulfinyl radical, wherein alkyl is as defined above.

The term "aralkyl" refers to an aryl substituted alkyl radical. Preferred aralkyl radicals are "lower aralkyl" radicals in which aryl radicals are attached to alkyl radicals having 1 to 6 carbon atoms. Examples of such radicals include benzyl, diphenylmethyl, triphenylmethyl, phenylethyl and diphenylethyl. The terms benzyl and phenylmethyl are interchangeable.

The term “heteroaralkyl” means a heteroaryl substituted alkyl radical, which means that the heteroaralkyl radical may be optionally substituted with at least three substituents as defined in the aralkyl radical above. The term "perhaloaralkyl" means an aryl substituted alkyl radical, which is substituted with at least three halo radicals as defined above.

The term "aralkylsulfinyl" means an aralkyl radical attached to a sulfinyl radical, where aralkyl is as defined above. "Aralkylsulfinylalkyl" means an aralkylsulfinyl radical attached to an alkyl radical, wherein alkyl is as defined above.

The term "aralkylsulfonyl" means an aralkyl radical attached to a sulfonyl radical, where aralkyl is as defined above. "Aralkylsulfonylalkyl" means an aralkylsulfonyl radical, wherein alkyl is as defined above, attached to an alkyl radical.

The term "cycloalkyl" means a radical having 3 to 15 carbon atoms. More preferred cycloalkyl radicals are "lower cycloalkyl" radicals having 3 to 7 carbon atoms. Examples include radicals such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. The term "cycloalkyl" means a radical having 7 to 15 carbon atoms and having 2 to 4 rings. Examples include radicals such as norbornyl (ie bicyclo [2.2.1] heptyl) and adamantyl. The term "cycloalkylalkyl" refers to a cycloalkyl substituted alkyl radical. Preferred cycloalkylalkyl radicals are "lower cycloalkylalkyl" radicals having a cycloalkyl radical attached to an alkyl radical having 1 to 6 carbon atoms. Examples of such radicals include cyclohexylhexyl. The term "cycloalkenyl" means a radical having from 3 to 10 carbon atoms and having at least one carbon-carbon double bond. Preferred cycloalkenyl radicals are "lower cycloalkenyl" radicals having 3 to 7 carbon atoms. Examples include radicals such as cyclobutenyl, cyclopentenyl, cyclohexenyl and cycloheptenyl. The term "halocycloalkyl" means a radical in which any one or more cycloalkyl carbon atoms are substituted with halo as defined above. Specifically included are monohalocycloalkyl, dihalocycloalkyl and polyhalocycloalkyl radicals. For example, a monohalocycloalkyl radical may have one of the bromo, chloro or fluoro atoms in that radical. Dihalo radicals may have two or more of the same halo atoms or a combination of different halo radicals, and polyhalocycloalkyl radicals may have more than two of the same halo atoms or a combination of different halo radicals. More preferred halocycloalkyl radicals are "lower halocycloalkyl" radicals having 3 to about 8 carbon atoms. Examples of such halocycloalkyl radicals include fluorocyclopropyl, difluorocyclobutyl, trifluorocyclopentyl, tetrafluorocyclohexyl and dichlorocyclopropyl. The term "halocycloalkenyl" means a radical wherein any one or more cycloalkenyl carbon atoms are substituted with halo as defined above. Specifically included are monohalocycloalkenyl, dihalocycloalkenyl and polyhalocycloalkenyl radicals.

The term "cycloalkoxy" means a cycloalkyl radical attached to an oxy radical. Examples of such radicals include cyclohexoxy and cyclopentoxy. In addition, the term "cycloalkoxyalkyl" means an alkyl radical wherein at least one cycloalkoxy radical is attached to an alkyl radical, that is to say an alkyl radical which forms a monocycloalkoxyalkyl and a dicycloalkoxyalkyl radical. Examples of such radicals include cyclohexoxyethyl. "Cycloalkoxy" radicals may be further substituted with one or more halo atoms such as fluoro, chloro or bromo to provide "halocycloalkoxy" and "halocycloalkoxyalkyl" radicals.

The term "cycloalkylalkoxy" means a cycloalkyl radical attached to an alkoxy radical. Examples of such radicals include cyclohexylmethoxy and cyclopentylmethoxy.

The term "cycloalkenyloxy" means a cycloalkenyl radical attached to an oxy radical. Examples of such radicals include cyclohexenyloxy and cyclopentenyloxy. The term "cycloalkenyloxyalkyl" also refers to alkyl radicals in which one or more cycloalkenyloxy radicals are attached to an alkyl radical, that is to say an alkyl radical that forms a monocycloalkenyloxyalkyl and dicycloalkenyloxyalkyl radical. it means. Examples of such radicals include cyclohexenyloxyethyl. "Cycloalkenyloxy" radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide "halocycloalkenyloxy" and "halocycloalkenyloxyalkyl" radicals.

The term "cycloalkylenedioxy" radical refers to a cycloalkylene radical in which two or more oxygens are bonded to a single cycloalkylene group. Examples of “alkylenedioxy” radicals include 1,2-dioxycyclohexylene.

The term "cycloalkylsulfinyl" means a cycloalkyl radical attached to a sulfinyl radical, wherein cycloalkyl is as defined above. "Cycloalkylsulfinylalkyl" means a cycloalkylsulfinyl radical, wherein alkyl is as defined above, attached to an alkyl radical. The term "cycloalkylsulfonyl" means a cycloalkyl radical attached to a sulfonyl radical, where cycloalkyl is as defined above. "Cycloalkylsulfonylalkyl" means a cycloalkylsulfonyl radical, wherein alkyl is as defined above, attached to an alkyl radical.

The term "cycloalkylalkanoyl" means a radical wherein at least one cycloalkyl carbon atom is substituted with at least one carbonyl radical as defined below. Specifically included are monocarbonylcycloalkyl and dicarbonylcycloalkyl radicals. Examples of monocarbonylcycloalkyl radicals include cyclohexylcarbonyl, cyclohexylacetyl and cyclopentylcarbonyl. Examples of dicarbonylcycloalkyl radicals include 1,2-dicarbonylcyclohexane.

The term "alkylthio" means a radical attached to a divalent sulfur atom and containing a linear or branched alkyl radical having 1 to 10 carbon atoms. More preferred alkylthio radicals are "lower alkylthio" radicals having 1 to 6 carbon atoms. An example of "lower alkylthio" is methylthio (CH ₃ -S-). "Alkylthio" radicals may be further substituted with one or more halo atoms such as fluoro, chloro or bromo to provide a "haloalkylthio" radical. Examples of such radicals are fluoromethylthio, chloromethylthio, trifluoromethylthio, difluoromethylthio, trifluoroethylthio, fluoroethylthio, tetrafluoroethylthio, pentafluoroethylthio and fluoro Ropropylthio is included.

The term "alkyl aryl amino" means a radical having from 1 to 10 carbon atoms, both linear or branched alkyl radicals and one aryl radical attached to the amino radical. Examples include N-methyl-4-methoxyaniline, N-ethyl-4-methoxyaniline and N-methyl-4-trifluoromethoxyaniline.

The term alkylamino refers to “monoalkylamino” and “dialkylamino” in which one or two alkyl radicals are each attached to an amino radical.

The term arylamino refers to "monoarylamino" and "diarylamino", in which one or two aryl radicals are each attached to an amino radical. Examples of such radicals include N-phenylamino and N-naphthylamino.

The term "aralkylamino" means an aralkyl radical attached to an amino radical, where aralkyl is as defined above. The term aralkylamino refers to “monoararylamino” and “diaralkylamino” in which one or two aralkyl radicals are each attached to an amino radical. The term aralkylamino also refers to “monoaralkyl monoalkylamino” in which one alkyl radical and one aralkyl radical are attached to the amino radical.

The term "arylsulfinyl" means a radical to which an aryl radical as defined above is attached to a divalent S (O) atom. The term "arylsulfinylalkyl" refers to an arylsulfinyl radical attached to a linear or branched alkyl radical having 1 to 10 carbon atoms.

The term "arylsulfonyl" means an aryl radical attached to a sulfonyl radical, where aryl is as defined above. "Arylsulfonylalkyl" means an arylsulfonyl radical, wherein alkyl is as defined above, attached to an alkyl radical. The term “heteroarylsulfinyl” means a radical to which a heteroaryl radical as defined above is attached to a divalent S (O) atom. The term “heteroarylsulfinylalkyl” refers to a heteroarylsulfinyl radical attached to a linear or branched alkyl radical having 1 to 10 carbon atoms. The term "heteroarylsulfonyl" means a heteroaryl radical attached to a sulfonyl radical, where heteroaryl is as defined above. "Heteroarylsulfonylalkyl" means a heteroarylsulfonyl radical attached to an alkyl radical, wherein alkyl is as defined above.

The term "aryloxy" means an aryl radical as defined above, attached to an oxygen atom. Examples of such radicals are phenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 3-chloro-4-ethylphenoxy, 3,4-dichlorophenoxy, 4-methylphenoxy , 3-trifluoromethoxyphenoxy, 3-trifluoromethylphenoxy, 4-fluorophenoxy, 3,4-dimethylphenoxy, 5-bromo-2-fluorophenoxy, 4-bro Parent-3-fluorophenoxy, 4-fluoro-3-methylphenoxy, 5,6,7,8-tetrahydronaphthyloxy, 3-isopropylphenoxy, 3-cyclopropylphenoxy, 3- Ethyl phenoxy, 3-pentafluoroethylphenoxy, 3- (1,1,2,2-tetrafluoroethoxy) phenoxy and 4-tert-butylphenoxy.

The term "aroyl" means an aryl radical as defined above, attached to a carbonyl radical as defined above. Examples of such radicals include benzoyl and toluoyl.

The term "arkanoyl" means an aralkyl radical as defined above, attached to a carbonyl radical as defined above. Examples of such radicals include phenylacetyl.

The term "aralkoxy" means an oxy containing aralkyl radical, attached to another radical via an oxygen atom. More preferred aralkoxy radicals are "lower alkoxy" radicals with phenyl radicals attached to lower alkoxy radicals as defined above. Examples of such radicals are benzyloxy, 1-phenylethoxy, 3-trifluoromethoxybenzyloxy, 3-trifluoromethylbenzyloxy, 3,5-difluorobenzyloxy, 3-bromobenzyloxy, 4 -Propylbenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy and 2-phenylethoxy.

The term "aryloxyalkyl" means an aryloxy radical as defined above, attached to an alkyl group. Examples of such radicals include phenoxymethyl.

The term "haloaryloxyalkyl" means an aryloxyalkyl radical as defined above, wherein from one to five halo radicals are attached to an aryloxy group.

The term “heteroaroyl” means a heteroaryl radical as defined above, attached to a carbonyl radical as defined above. Examples of such radicals include furoyl and nicotinyl.

The term “heteroarkanoyl” means a heteroaralkyl radical as defined herein, attached to a carbonyl radical as defined above. Examples of such radicals include pyridylacetyl and furylbutyryl.

The term "heteroaralkoxy" means an oxy containing heteroaralkyl radical, attached to another radical via an oxygen atom. More preferred heteroaralkoxy radicals are "lower heteroaralkoxy" radicals with heteroaryl radicals attached to lower alkoxy radicals as defined above.

The term "haloheteroaryloxyalkyl" means a heteroaryloxyalkyl radical as defined above wherein one to four halo radicals are attached to a heteroaryloxy group.

The term “heteroarylamino” means a heterocyclyl radical as defined above, attached to an amino group. Examples of such radicals include pyridylamino.

The term "heteroarylaminoalkyl" means a heteroarylamino radical as defined above, attached to an alkyl group. Examples of such radicals include pyridylmethylamino.

The term "heteroaryloxy" means a heterocyclyl radical as defined above, attached to an oxy group. Examples of such radicals include 2-thiophenyloxy, 2-pyrimidyloxy, 2-pyridyloxy, 3-pyridyloxy and 4-pyridyloxy.

The term “heteroaryloxyalkyl” means a heteroaryloxy radical as defined above, attached to an alkyl group. Examples of such radicals include 2-pyridyloxymethyl, 3-pyridyloxyethyl and 4-pyridyloxymethyl.

The term "arylthio" means an aryl radical as defined above, attached to a sulfur atom. Examples of such radicals include phenylthio.

The term "arylthioalkyl" means an arylthio radical as defined above, attached to an alkyl group. Examples of such radicals include phenylthiomethyl.

The term "alkylthioalkyl" means an alkylthio radical as defined above, attached to an alkyl group. Examples of such radicals include methylthiomethyl. The term "alkoxyalkyl" means an alkoxy radical, as defined above, attached to an alkyl group. Examples of such radicals include methoxymethyl.

The term "carbonyl" refers to a carbon radical in which two of the four covalent bonds share one oxygen atom. The term "carboxy" means a hydroxy radical as defined above, attached to one of two non-covalent bonds in a carbonyl group. The term "carboxamide" refers to an amino, monoalkylamino, dialkylamino, monocycloalkylamino, alkylcycloalkylamino and dicycloalkylamino radical, attached to one of two non-covalent bonds in a carbonyl group. The term "carboxamidoalkyl" means a carboxamide radical as defined above, attached to an alkyl group. The term "carboxyalkyl" means a carboxy radical as defined above, attached to an alkyl group. The term "carbonalkoxy" means an alkoxy radical as defined above attached to one of two non-covalent bonds in a carbonyl group. The term "carboalkoxy" means an alkoxy radical as defined above, attached to one of two non-covalent bonds in a carbonyl group. The term "monocarboalkoxyalkyl" means one carboalkoxy radical as defined above, attached to an alkyl group. The term "dicarboalkoxyalkyl" means two carboalkoxy radicals as defined above attached to one alkylene group. The term "monocyanoalkyl" means one cyano radical as defined above, attached to an alkyl group. The term "dicyanoalkylene" means two cyano radicals as defined above attached to one alkyl group. The term "carboalkoxycyanoalkyl" means one cyano radical as defined above, attached to a carboalkoxyalkyl group.

The term "acyl" alone or in combination, for example, hydrido, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkoxyalkyl, haloalkoxy, aryl, heterocyclyl, heteroaryl, alkylsulfinylalkyl, A car bound to a radical selected from alkylsulfonylalkyl, aralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, alkylthio, arylthio, amino, alkylamino, dialkylamino, aralkoxy, arylthio and alkylthioalkyl By carbonyl or thionocarbonyl group is meant. Examples of "acyl" include formyl, acetyl, benzoyl, trifluoroacetyl, phthaloyl, malonyl, nicotinyl and the like. The term "haloalkanoyl" means one or more halo radicals defined herein, attached to an alkanoyl radical as defined above. Examples of such radicals include chloroacetyl, trifluoroacetyl, bromopropanoyl and heptafluorobutanoyl.

The term "phosphono" means pentavalent phosphorus attached to an oxygen radical with two covalent bonds. The term "dialkoxyphosphono" refers to two alkoxy radicals as defined above attached to one phosphono radical by two covalent bonds. The term "dialkoxyphosphono" refers to two aralkoxy radicals as defined above attached to one phosphono radical by two covalent bonds. The term "dialkoxyphosphonoalkyl" refers to a dialkoxyphosphono radical as defined above attached to an alkyl radical. The term "dialkoxyphosphonoalkyl" refers to a dialkoxyphosphono radical as defined above, attached to an alkyl radical.

The term "amino" refers to a nitrogen atom which has one covalent bond available for bonding to a single atom such as carbon and contains two substituents such as hydrido, hydroxy or alkyl. Examples of such amino radicals include -NH _2- , -NHCH _3- , -NHOH-, and -NHOCH _3- . The term "imino" refers to a nitrogen atom which has two covalent bonds available for bonding to a single atom such as carbon and contains one substituent such as hydrido, hydroxy or alkyl. Examples of such imino radicals include = NH, = NCH ₃ , = NOH and = NOCH ₃ . The term "imino carbonyl" refers to a carbon radical which shares two of its four covalent bond sites with an imino group. Examples of such imino carbonyl radicals include C = NH, C = NCH ₃ , C = NOH and C = NOCH ₃ . The term "amidino" means a substituted or unsubstituted amino group attached to one of the two available bonds of the iminocarbonyl radical. Examples of such amidino radicals include, but are not limited to include _{NH 2 -C = NH, NH 2} -C = NCH 3, NH 2 -C = NOCH 3 , and CH ₃ NH-C = NOH. The term "guanidino" means an amidino group bonded to an amino group as defined above, wherein the amino group may be bonded to a third group. Examples of such guanidino radicals are NH ₂ -C (NH) -NH-, NH ₂ -C (NCH ₃ ) -NH-, NH ₂ -C (NOCH ₃ ) -NH- and CH ₃ NH-C (NOH). ) -NH- is included.

The term "sulfonium" refers to a positively charged trivalent sulfur atom, which sulfur is substituted with three groups based on carbon such as alkyl, alkenyl, aralkyl or aryl. The term "dialkyl sulfonium" refers to a sulfonium group in which the sulfur is substituted with two alkyl groups. Examples of such dialkylsulfonium radicals include (CH ₃ ) ₂ S ⁺ -. The term "dialkyl sulfonium alkyl" refers to a dialkyl sulfonium group bonded to one bond of an alkylene group as defined above. Examples of such dialkylsulfoniumalkyl radicals include (CH ₃ ) ₂ S ⁺ -CH ₂ CH _2- .

The term "phosphonium" refers to a positively charged tetravalent phosphorus atom, which phosphorus is substituted with four groups based on carbon such as alkyl, alkenyl, aralkyl or aryl. The term "trialkyl phosphonium" refers to a phosphonium group in which phosphorus is substituted with three alkyl groups. Examples of such trialkylphosphonium radicals include (CH ₃ ) ₃ P ⁺ .

"Alkyl," alkenyl "," alkynyl "," alkanoyl "," alkylene "," alkenylene "," hydroxyalkyl "," haloalkyl "," haloalkylene "," halo "as defined above Alkenyl "," alkoxy "," alkenyloxy "," alkenyloxyalkyl "," alkoxyalkyl "," aryl "," perhaloaryl "," haloalkoxy "," haloalkoxyalkyl "," haloal Kenyloxy "," haloalkenyloxyalkyl "," alkylenedioxy "," haloalkylenedioxy "," heterocyclyl "," heteroaryl "," hydroxyhaloalkyl "," alkylsulfonyl ", "Haloalkylsulfonyl", "alkylsulfonylalkyl", "haloalkylsulfonylalkyl", "alkylsulfinyl", "alkylsulfinylalkyl", "haloalkylsulfinylalkyl", "aralkyl", "hetero Aralkyl "," perhaloaralkyl "," aralkylsulfonyl "," aralkylsulfonylalkyl "," aralkylsulfinyl "," aralkylsulfinylalkyl "," cycloalkyl "," cycloalkylalka Noyl "," cycloalkylalkyl "," cycloalkenyl "," halocycloalkyl "," halocycloalkenyl ", "Cycloalkylsulfinyl", "cycloalkylsulfinylalkyl", "cycloalkylsulfonyl", "cycloalkylsulfonylalkyl", "cycloalkoxy", "cycloalkoxyalkyl", "cycloalkylalkoxy", "cycloal Kenyloxy "," cycloalkenyloxyalkyl "," cycloalkylenedioxy "," halocycloalkoxy "," halocycloalkoxyalkyl "," halocycloalkenyloxy "," halocycloalkenyloxyalkyl "," Alkylthio "," haloalkylthio "," alkylsulfinyl "," amino "," oxy "," thio "," alkylamino "," arylamino "," aralkylamino "," arylsulfinyl ", "Arylsulfinylalkyl", "arylsulfonyl", "arylsulfonylalkyl", "heteroarylsulfinyl", "heteroarylsulfinylalkyl", "heteroarylsulfonyl", "heteroarylsulfonylalkyl", "Heteroarylamino", "heteroarylaminoalkyl", "heteroaryloxy", "heteroaryloxyalkyl", "aryloxy", "aroyl", "aralkanoyl", "arkoxy", "aryloxy Kil "," haloaryloxyalkyl "," heteroaroyl "," heteroarkanoyl "," heteroarkoxy "," heteroarkoxyalkyl "," arylthio "," arylthioalkyl "," alkoxyalkyl The "," acyl "," amidino "," guanidino "," dialkylsulfonium "," trialkylphosphonium "and" dialkylsulfoniumalkyl "groups are one or more non-hydrides as follows. And may optionally have substituents: amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, ar Alkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino -N-alkylamino, heteroarylaminoalkyl, heteroaryloxy, heteroaryloxyalkyl, ha Alkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxyalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy Halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, aryl Thioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkyl Sulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoaryl Amidosulfonyl, arylsulfonamido, diaryl amidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, alkanoyl, alkenoyl , Aroyl, heteroaroyl, aralkanoyl, heteroarkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalkyl, alkylenedioxy, haloalkylenedioxy, cycloalkyl, Cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl, Hydroxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxy Kyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarbonyl, carboalkoxy, carboxamido, carboxamidoalkyl, cyano, carbohalo Alkoxy, phosphono, phosphonoalkyl, dialkoxyphosphono and dialalkoxyphosphonoalkyl.

The term "spacer" may include linear moieties and covalent bonds having a backbone of 1 to 7 adjacent atoms. The spacer may have 1 to 7 atoms of a monovalent or polyvalent chain. The monovalent chain may consist of radicals selected from the following: = C (H)-, = C (R ^2a )-, -O-, -S-, -S (O)-, -S (O) _2- , -NH-, -N (R ^2a )-, -N =, -CH (OH)-, = C (OH)-, -CH (OR ^2a )-, = C (OR ^2a )-, and -C ( O)-(where R ^2a is alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, aryloxyalkyl, alkoxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, Haloalkenyl, haloalkoxyalkyl, perhaloaralkyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthioalkyl and heteroarylalkenyl). Multivalent chains may consist of straight chains of one or two or three or four or five or six or seven atoms or straight and side chains of one or two or three or four or five or six atoms. The chain may consist of one or more radicals selected from the following and many other radicals defined above or commonly known or identified to those skilled in the art: lower alkylene, lower alkenyl, -O-, -O-CH _2- , -S-CH _2- , -CH ₂ CH _2- , ethenyl, -CH = CH (OH)-, -OCH ₂ O-, -O (CH ₂ ) ₂ O-, -NHCH _2- , -OCH (R ^2a ) O-, -O (CH ₂ CHR ^2a ) O-, -OCF ₂ O-, -O (CF ₂ ) ₂ O-, -S-, -S (O)-, -S (O) _2- , -N (H)-, -N (H) O-, -N (R ^2a ) O-, -N (R ^2a )-, -C (O)-, -C (O) NH-, ^{-C (O) NR 2a -,} -N =, -OCH 2 -, -SCH 2 -, -S (O) CH 2 -, -CH 2 C (O) -, -CH (OH) -, = C (OH)-, -CH (OR ^2a )-, = C (OR ^2a )-, S (O) ₂ CH ₂ -and -NR ^2a CH _2- . The side chain may include one or more bihydrido substituents, such as the following substituents: amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, perhaloarlalkyl, aralkyl Sulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl , Heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, heteroaryloxy, heteroaryloxyalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxyalkyl, heteroaralkoxy , Cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, Halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxy Alkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkyl Sulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoaryl amidosulfonyl, arylsulfonamido, diaryl amidosulfonyl, monoalkyl mono Aryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroarka Noyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalkyl, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, Halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl, hydroxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy , Aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy Carboalkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, dialkoxyphosphono and dialkoxyphosphonoalkyl.

The compounds of the present invention may exist in tautomers, geometric or stereoisomeric forms. The present invention, cis- and trans geometric isomers, E- and Z geometric isomers, R- and S enantiomers, diastereomers, d-isomers, l-isomers, racemic mixtures thereof, so long as they fall within the scope of the invention. And all such compounds, including other mixtures thereof. Also included in the present invention are pharmaceutically acceptable salts of such tautomers, geometric or stereoisomeric forms.

The terms "cis" and "trans" refer to the form of geometric isomers in which two carbon atoms connected by a double bond each have a hydrogen atom on the same side of the double bond ("cis") or on the opposite side of the double bond ("trans").

Some of the compounds described contain alkenyl groups, meaning that they include both cis and trans or "E" and "Z" geometric forms.

Some of the compounds described include one or more stereocenters, which means that for each stereocenter present, it contains R, S, and a mixture of R and S forms.

Some of the compounds described herein may include one or more ketone or aldehyde carbonyl groups or combinations thereof, alone or as part of a heterocyclic ring system. Such carbonyl groups may be present in part or mainly in one or more "enol" forms of each aldehyde and ketone group present, and in part or mainly in "keto" forms. Compounds of the present invention having aldehyde or ketone carbonyl groups are meant to include both "keto" and "enol" tautomeric forms.

Some of the compounds described herein may include one or more amide carbonyl groups or combinations thereof, alone or as part of a heterocyclic ring system. Such carbonyl groups may be present in part or mainly in one or more "enol" forms of each amide group present and in part or mainly in "keto" forms. Compounds of the present invention having amidated carbonyl groups are meant to include both "keto" and "enol" tautomeric forms. The amide carbonyl group may be in the form of both oxo (C═O) and thiono (C═S).

Some of the compounds described herein may contain one or more imine or enamine groups or combinations thereof. Such groups may exist in part or mainly in one or more "enamine" forms of each group present and in part or mainly in "imine" forms. The compounds of the present invention having the imine or enamine groups mean that both "imine" and "enamine" tautomer forms are included.

The invention also provides for the treatment of various thrombotic symptoms, including coronary and cerebrovascular diseases of a subject, comprising administering to a subject with a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof: Treatment and prophylaxis in anticoagulant therapy for prevention include:

[Formula I]

In another embodiment, a compound of formula (I) or a pharmaceutically acceptable salt thereof of the present invention as defined above has a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof of the present invention having the following Included in the treatment and prevention of coronary artery disease, cerebrovascular disease and other coagulation cascade related abnormalities in the subject, including administration to the subject.

In addition, the compounds of formula (I) or pharmaceutically acceptable salts thereof of the present invention can be used whenever inhibition of blood coagulation is required to prevent coagulation of stored whole blood and to prevent coagulation of other test or storage biological samples. Thus, the coagulation inhibitors of the present inhibition are for example when the blood of the mammal is in contact with a substance selected from the group consisting of vascular grafts, stents, orthopedic prosthesis, cardiac prostheses and extracorporeal circulatory devices. As such, for the purpose of inhibiting blood coagulation, and any medium that contains or is thought to contain plasma coagulation factors and can be added or contacted.

Compounds of formula (I) can inhibit the activity of serine proteases in relation to coagulation cascades, thus making pharmaceuticals, methods of prophylactic or therapeutic treatment of diseases mediated by coagulation cascade serine proteases, such as mammals, blood, blood products and It can be used for platelet aggregate formation, fibrin formation, thrombus formation and embolism inhibition in mammalian organs. In addition, the compounds may be used in mammals with unstable angina, refractory angina, myocardial infarction, transient ischemic attack, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, intraocular fibrin accumulation, and re It can be used to treat or prevent reclosure or restenosis of communicating blood vessels. The compounds are also used to study the mechanism of action of the coagulation cascade serine protease, allowing the design of better inhibitors and the development of better assays. The compounds of formula I will also be used for the prevention of cerebrovascular accidents (CVAs) or strokes.

Also included in the compound class of Formula I are pharmaceutically acceptable salts thereof. The term "pharmaceutically acceptable salts" means salts conventionally used for the formation of alkali metal salts and the addition salts of free acids or free bases. The nature of the salt is not critical and is provided as pharmaceutically acceptable. Suitable pharmaceutically acceptable acid addition salts of compounds of formula (I) can be prepared from inorganic or organic acids. Examples of the inorganic acid include hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, carbonic acid, sulfuric acid and phosphoric acid. Suitable organic acids are selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic acid and sulfonic acid types of organic acids, examples of organic acids are formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, gluconic acid. , Lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, gluconic acid, maleic acid, fumaric acid, pyruvic acid, aspartic acid, glutamic acid, benzoic acid, anthlanic acid, mesylic acid, salicylic acid, p-hydroxybenzoic acid, phenylacetic acid , Mandelic acid, embonic acid (pamoic acid), methanesulfonic acid, ethylsulfonic acid, benzenesulfonic acid, sulfanilic acid, stearic acid, cyclohexylaminosulfonic acid, algenic acid, galacturonic acid. Suitable pharmaceutically acceptable base addition salts of compounds of formula I include metal salts made of aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or N, N'-dibenzylethylenediamine, choline, chloroprocaine, Organic salts made from diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. All these salts can be prepared by conventional means from the corresponding compounds of formula (I), for example by reacting a suitable acid or base with the compound of formula (I).

The present invention also encompasses pharmaceutical compositions containing a therapeutically effective amount of one or more pharmaceutically acceptable carriers, adjuvants or diluents with a compound of formula (I). The pharmaceutical composition of the present invention is formula (I), in combination with one or more non-toxic, pharmaceutically acceptable carriers and / or diluents and / or adjuvants (hereinafter collectively referred to as "carrier" substances), together with other active ingredients, if necessary It may contain an active compound of. The active compounds of the present invention can be administered by any suitable route, preferably in the form of a pharmaceutical composition adapted for such route, and in dosages effective for the intended treatment.

The active compounds and compositions can be administered, for example, orally, intravascularly, intraperitoneally, subcutaneously, intramuscularly, ocular or topically. For the treatment of intraocular fibrin accumulation, the compounds may be administered orally or parenterally, as well as intraocular or topically.

The compounds may be administered in the form of depot injections or implant preparations which may be formulated in such a way that the active ingredient is released slowly. The active ingredient may be compressed into pellets or small cylinders and injected subcutaneously or intramuscularly as depot injections or implants. Implants may use inert materials such as biodegradable polymers or synthetic silicones such as Silastic, silicone rubber or other silicon containing polymers.

In addition, the compounds may be administered in the form of liposome transport systems, such as small monolayer vesicles, large monolayer vesicles and multilayer vesicles. Liposomes can be formed from various phospholipids such as cholesterol, stearylamine or phosphatidylcholine.

In addition, the compounds may be transported using monoclonal antibodies as individual carriers to which the compound molecules are coupled. In addition, the compounds may be coupled with soluble polymers that are targeted drug carriers. Such polymers include polyvinylpyrrolidone, pyran copolymers, polyhydroxy-propyl-methacrylamide-phenols, polyhydroxyethyl-aspartamide-phenols, or polyethyleneoxide-polylysine substituted with palmitoyl residues. May be included. The compounds also contain biodegradable polymers useful for achieving controlled release of drugs, such as polylactic acid, polyglycolic acid, copolymers of polylactic acid and polyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters , Polyacetals, polydihydropyrans, polycyanoacrylates, and crosslinked or amphoteric block copolymers of hydrogels.

For oral administration, the pharmaceutical compositions may be, for example, tablets, capsules (each capsule comprising a sustained release or timed release formulation), pills, powders, granules, elixirs, tinctures, suspensions , Solutions including syrups, and emulsions. Pharmaceutical compositions are preferably prepared in the form of dosage units containing a specific amount of the active ingredient. Examples of such dosage units are tablets or capsules. The active ingredient may also be administered by injection as a composition using, for example, saline, dextrose or water as a suitable carrier.

The dosage regimen and amount of therapeutically active compound administered for treating a disease symptom with a compound and / or composition of the present invention may vary depending on the age, weight, sex and medical condition of the subject, the severity of the disease, the route and frequency of administration, and the particular used It depends on a variety of factors, including compounds, and therefore can vary widely.

The pharmaceutical composition may contain the active ingredient in the range of about 0.1 to 2000 mg, preferably about 0.5 to 500 mg. A daily dosage of about 0.01 to 100 mg / kg body weight, preferably about 0.5 to about 20 mg / kg body weight may be appropriate. The daily dose may be administered in one to four doses daily.

The present compounds can be used as topical ointments, containing the active ingredient in a total amount of, for example, 0.075 to 30% w / w, preferably 0.2 to 20% w / w, most preferably 0.4 to 15% w / w It may be formulated as a cream or as a suppository. When formulated into an ointment, the active ingredient can be used with either paraffinic or water miscible ointment bases.

Alternatively, the active ingredient may be formulated into a cream with an oil-in-water cream base. If desired, the cream-based aqueous phase may comprise, for example, at least 30% w / w polyhydric alcohols such as propylene glycol, butane-1,3-diol, mannitol, sorbitol, glycerol, polyethylene glycol and mixtures thereof. have. Topical formulations may preferably contain compounds which enhance the absorption or penetration of the active ingredient through the skin or other application sites. Examples of such skin penetration enhancers include dimethylsulfoxide and related analogs. In addition, the compounds of the present invention may be administered by a transdermal device. Preferably, topical administration will be performed using patches in either the reservoir and porous membrane form or solid matrix variants. In either case, the active agent is continuously transported from the reservoir or microcapsules through the membrane into the active agent permeable adhesive in contact with the subject's skin or mucosal layer. When the active agent is absorbed through the skin, the controlled and predetermined flow rate of the active agent is administered to the subject. In the case of microcapsules, the encapsulating agent may also function as a membrane.

The oily phase of the emulsions of the invention may be formulated in a known manner from known ingredients. The phase may contain only emulsifiers, but may contain one or more emulsifiers and a mixture of fats, oils or both fats and oils. Preferably, a hydrophilic emulsifier is included together with a lipophilic emulsifier that acts as a stabilizer. It is also desirable to include both oils and fats. In addition, the emulsifier (s) with or without stabilizer (s) constitute the so-called emulsifying wax, and together with the oils and fats constitute the so-called emulsifying ointment substrate, which forms the oily dispersed phase of the cream formulation. . Suitable emulsifiers and emulsion stabilizers for use in the formulations of the present invention include, among others, Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate and sodium lauryl sulfate.

The choice of oils or fats suitable for the formulation is based on achieving the desired cosmetic properties because of the very low solubility of the active compounds in most of the oils commonly used in pharmaceutical emulsion formulations. Thus, the cream should be a product that is not greasy, uncontaminated, and washable, preferably having a consistency that is suitable to avoid leakage from tubes or other containers. Straight or branched chain, mono or dibasic alkyl esters such as diisoadiate, isocetyl stearate, propylene glycol diesters of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2 Combinations of ethylhexyl palmitate or branched chain esters may be used. These may be used alone or in combination depending on the properties required. Alternatively, high melting lipids such as white soft paraffin and / or liquid paraffin or other mineral oils may be used.

For therapeutic purposes, the active compounds of the invention are usually combined with one or more adjuvants appropriate for the route of administration required. When orally administered, the compounds are lactose, sucrose, starch powder, cellulose esters of alkanoic acid, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric acid and sulfuric acid, gelatin, acacia After being mixed with rubber, sodium alginate, polyvinylpyrrolidone and / or polyvinyl alcohol, it may be tableted or encapsulated for convenient administration. The capsule or tablet may comprise a controlled release formulation such as may be provided as a dispersion of the active compound in hydroxypropylmethyl cellulose. Formulations for parenteral administration may be in the form of aqueous or non-aqueous isotonic sterile infusion solutions or suspensions. These solutions and suspensions may be prepared from sterile powders or granules having one or more of the carriers or diluents mentioned for use in the formulation for oral administration. The compound can be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride and / or various buffers. Other adjuvants and dosage forms are well known in the pharmaceutical art.

In practicing the methods of the present invention for the treatment and prevention of various thrombotic symptoms, including coronary and cerebrovascular diseases, the compounds and pharmaceutical compositions of the present invention, alone or in combination with others, or other therapeutic agents or in vivo It is administered in combination with a diagnostic agent. In addition, the coagulation cascade inhibitors of the present invention may be administered with suitable antiplatelet aggregation agents, including but not limited to, the treatment or prevention of atherosclerosis: ticlopidine or clopidrogel, fibrinogen receptor Antagonists (e.g. to treat or prevent unstable angina or to prevent reblocking and restenosis after angioplasty), anticoagulants such as aspirin, warfarin or heparin, plasminogen for obtaining synergistic effects in the treatment of various pathologies Activators or thrombolytics such as streptokinase, lipid lowering agents, including anti-cholesterol hyperemia (eg, HMG CoA reductase inhibitors such as mevastatin, lovastatin, simvastatin, pravastatin and fluvastatin, HMG CoA synthetase inhibitors, etc.), Antidiabetics or other cardiovascular agents [loop diuretics, te Azide diuretics, nitrates, aldosterone antagonists (such as spironolactone and epoxymexlelenone), angiotensin converting enzymes (such as ACE) inhibitors, angiotensin II receptor antagonists, beta blockers, antiarrhythmic agents, antihypertensives and calcium channel blockers ]. For example, patients suffering from coronary artery disease and patients undergoing angioplasty will benefit from administering the fibrinogen receptor antagonist and the coagulation cascade inhibitor of the invention together. In addition, coagulation cascade inhibitors can enhance the efficacy of tissue plasminogen activator mediated thrombolytic reperfusion.

Conventional dosages of the coagulation cascade inhibitors of the invention in combination with other antiplatelet agents, anticoagulants, cardiovascular therapies or thrombolytic agents, depending on the treatment needs of the patient, are without coadministration of additional antiplatelet, anticoagulant, cardiovascular or thrombolytic agents. It may be the same as the usual dose of the coagulation cascade inhibitor administered or may be substantially lower than the usual dose of the coagulation cascade inhibitor administered without coadministration of additional antiplatelet, anticoagulant, cardiovascular or thrombolytic agents.

All references mentioned are incorporated by reference as recorded herein.

Although the present invention has been described in terms of specific embodiments, the detailed description of these embodiments is not considered to be limiting. The invention is illustrated by the following examples which are not intended to limit the scope of the invention. Without further elaboration, one skilled in the art would, using the preceding description, utilize the present invention to its fullest extent. Accordingly, the following preferred specific embodiments are to be considered merely descriptive, and any method is not a limitation on the remainder of the specification. In addition, compounds have been devised that include various changes in the schemes or structural modifications depicted in the Examples below. Those skilled in the art will readily understand that known variations of the conditions and processes of the following preparation methods can be used to prepare these compounds.

Those skilled in the art can use these general methods for preparing the specific examples below, and examples can be suitably characterized or characterized by ¹ H NMR, mass spectrometer, elemental composition, and similar methods. In addition, these compounds may be formed in vivo. The following examples include detailed descriptions of methods for the preparation of compounds of formula (I). These detailed descriptions fall within the scope of the present invention and exist for descriptive purposes only and are not intended as a limitation on the scope of the present invention. Unless otherwise indicated, all parts are parts by weight and temperature is in degrees Celsius.

The following general synthetic sequences are useful for practicing the present invention. Abbreviations used in the schemes and tables include the following: "AA" stands for amino acid, "AcCN" stands for acetonitrile, "AcOH" for acetic acid, "BINAP" for 2,2'-bis (diphenylphosphino) ) -1,1'-binafyl, "BnOH" is benzyl alcohol, "BnCHO" is 2-phenylethanal, "BnSO ₂ Cl" is benzylsulfonyl chloride, "Boc" is tert-butyloxycarbonyl, "BOP" is benzotriazol-1-yl-oxy-tris- (dimethylamino), "bu" is butyl, "dba" is dibenzylideneacetone, and "DCC" is 1,3-dicyclohexylcarbodiimide , "DCM" is dichloromethane or methylene chloride, "DIBAH" or "DIBAL" is diisobutylaluminum hydride, "DMF" is dimethylformamide, "DMSO" is dimethyl sulfoxide, "DPPA" is diphenylphosphoryl Azide, "EDC" is 1- [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride, "Ex. No." is example number, "Fmoc" is 9-fluorenylmethoxycarbide Bonyl, "HOBt" is hydroxyben Zoltriazole, "LDA" is lithium diisopropylamide, "MW" is molecular weight, "NMM" is N-methylmorpholine, "Ph" is phenyl or aryl, "PHTH" is phthaloyl group, "pnZ" is 4-nitrobenzyloxycarbonyl, "PTC" is phase transfer catalyst, "py" is pyridine, "RNH ₂ " is primary organic amine, "SEM" is 2- (trimethylsilyl) ethoxy-methyl chloride, "p- TsOH "is paratoluenesulfonic acid," TBAF "is tetrabutylammonium fluoride," TBTU "is 2- (1H-benzotriozol-1-yl) -1,1,3,3-tetramethyl uranium tetrafluoroborate , "TEA" is triethylamine, "TFA" is trifluoroacetic acid, "THF" is tetrahydrofuran, "TMS" is trimethylsilyl, "TMSCN" is trimethylsilyl cyanide, "Cbz" or "Z" Benzyloxycarbonyl.

General Synthesis Procedures and Specific Examples

A general synthetic approach to substituted uracil (ie pyrimidinedione) is shown in Scheme 1 below. Various N-1 substituted pyrimidinediones have been prepared and disclosed previously and are useful intermediates for the preparation of the compounds of the present invention. Stirring a solution of α-haloacetate and the N-1 substituted pyrimidinedione in dimethylsulfoxide in the presence of potassium carbonate results in alkylation of N-3 nitrogen. Reduction of the nitro functional group to the primary amine is readily performed using palladium on catalytic carbon in a hydrogen atmosphere. The primary amine can then be reacted with various raw materials, including but not limited to acid chloride, acid anhydride, sulfonyl chloride, alkyl and aromatic halides, aldehydes and ketones. The acetate ester can then be hydrolyzed with acid with lithium hydroxide. The acid is then coupled with a wide range of preferred amines under reference peptide coupling conditions. The amines used in the process of the present invention are usually multi-functional and react in protective form. Removal of such protecting groups provides a compound of the present invention.

General uracil procedure

The general uracil (ie pyrimidinedione) synthesis scheme is illustrated in Examples 1 and 2 below.

Example 1

Ex-1A) [Bampa, G. and Pecorari P. Boll. Chim. Farm. 1-benzyl-5-nitro-2,4 (1H, 3H) pyrimidinedione (6.14 g, 24.82 mmol) prepared as described in 1987, 126, 467-469, was dissolved in 100 ml dimethylsulfoxide, Potassium bicarbonate (3.78 g, 27.34 mmol) was added in one portion with stirring. After about 10 minutes, methyl bromoacetate (2.50 ml, 26.40 mmol) in 20 ml dimethylsulfoxide was added dropwise over a period of 10 minutes. Then the reaction mixture was heated to 40 ° C. and stirred for 18 hours. The reaction mixture was diluted with water (500 ml). The aqueous solution was extracted with ethyl acetate (4 x 100 ml). The combined organic solution was washed with water (1 x 150 ml), brine (2 x 150 ml). The organic solution was dried (MgSO ₄ ), filtered and concentrated to give an oil. The crude oil was purified by MPLC (20% ethyl acetate / hexane) to give pure 1-benzyl-3-methoxycarbonyl-methyl-5-nitro-2,4 (1H, 3H) pyrimidinedione (EX as white solid). -1A) was obtained in 81% yield.

EX-1B) solution of 1-benzyl-3-methoxycarbonylmethyl-5-nitro-2,4 (1H, 3H) pyrimidinedione (EX-1A; 6.30 g, 19.74 mmol) in 100.0 ml methanol Degassed with gas. The solution was then added to 5% Pd / C (0.737 g) and stirred for 24 hours under a hydrogen atmosphere at room temperature. The crude reaction was filtered through a Celite 545 pad and concentrated under reduced pressure. The oil was purified by MPLC (60% ethyl acetate / hexane) to give pure 5-amino-1-benzyl-3-methoxycarbonylmethyl-2,4 (1H, 3H) -pyrimidinedione (EX- as a tan solid). 1B) was obtained in 63% yield.

EX-1C) 5-amino-1-benzyl-3-methoxycarbonylmethyl-2,4 (1H, 3H) pyrimidinedione (EX-1B; 3.12 g, 10.77 mmol) tetrahydrofuran and dimethylformamide To a solution in 18.0 ml (1: 1, 0.62 M) was added N-methyl morpholine (3.60 ml, 32.74 mmol) at room temperature. The resulting mixture was cooled to 0 ° C. in an ice bath and stirred for 15 minutes. A solution of benzylsulfonyl chloride (2.26 g, 11.86 mmol) in 18.0 ml of tetrahydrofuran was added dropwise over 30 minutes. After the addition was complete, the reaction was stirred at 0 ° C for 3 h. The reaction mixture was diluted with ethyl acetate (250.0 ml) and washed with 1N HCl (2 × 50 ml), saturated NaHCO ₃ (2 × 50 ml) and brine (2 × 50 ml). The organic solution was dried (MgSO ₄ ), filtered and concentrated. Pure 1-benzyl-3-methoxycarbonylmethyl-5-[[(phenylmethyl) sulfonyl] amino] -2,4 (1H, 3H) pyrimidinedione as a white solid by polishing with ethyl acetate and hexane EX-1C) was obtained in 74% yield.

EX-1D) 1-benzyl-3-methoxycarbonylmethyl-5-[[(phenylmethyl) sulfonyl] amino] -2,4 (lH, 3H) pyrimidinedione (EX-1C; 3.28 g, 7.40 30.0 ml of 0.1 M lithium hydroxide in water were added to a suspension (1: 1, 0.078 M) in 94.0 ml of tetrahydrofuran and methanol. The suspension quickly clears and becomes uniform. The reaction was stirred for 1 hour and the volatiles were removed under reduced pressure. The remaining aqueous solution was cooled in an ice bath and acidified to pH 1 with 1.0 N HCl to form a white precipitate. The precipitate was collected by filtration, washed with 1.0 N HCl and water and dried under vacuum to afford pure 1-benzyl-3-methylene-carboxy-5-[[(phenylmethyl) sulfonyl] amino] -2,4 ( 1H, 3H) pyrimidinedione (EX-1D) was obtained in 99% yield.

EX-1E) of 1-benzyl-3-methylenecarboxy-5-[[(phenylmethyl) -sulfonyl] amino-2,4 (1H, 3H) pyrimidinedione (EX-1D; 531.6 mg, 1.238 mmol) N, N-diisopropylethylamine (1.10 ml, 6.315 mmol), N-hydroxybenzotriazole (499.6 mg, 3.697 mmol) in a solution (1: 1, 0.1 M) in 12.4 ml of tetrahydrofuran and dimethylformamide ), And 1- [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (717.2 mg, 3.741 mmol). The resulting mixture was stirred for 30 minutes. Then, the reaction mixture was added to the amine (623.3 mg, 2.500 mmol) in one portion. The resulting mixture was stirred overnight. The reaction mixture was diluted with ethyl acetate (50 ml) and washed with 5% citric acid (1 × 25 ml), saturated NaHCO ₃ (1 × 25 ml) and brine (1 × 25 ml). The organic solution was dried (MgSO ₄ ), filtered and concentrated. The crude reaction was purified by MPLC (75% ethyl acetate / hexanes) to afford product EX-1E.

A flask of protective pyrimidinedione (EX-1E) (238.5 mg, 0.3610 mmol) was added to 4.0 ml 4 M HCl in dioxane. The resulting solution was stirred overnight (about 18 hours). The solution was concentrated and the crude product was triturated from ethyl ether. The resulting white solid was collected by filtration, washed with ethyl ether and dried to give pure product.

Example 2

(EX-2A) tetrahydrofuran of 1-benzyl-3-methylenecarboxy-5-[[(phenylmethyl) sulfonyl] amino] -2,4 (1H, 3H) pyrimidinedione (439.8 mg, 1.024 mmol) And N, N-diisopropylethylamine (1.80 ml, 10.30 mmol), N-hydroxybenzotriazole (169.3 mg, 1.253 mmol) in a solution (1: 1, 0.1 M) in 10.0 ml of diethylformamide, And 1- [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (238.2 mg, 1.243 mmol). The resulting mixture was stirred for 10 minutes. The reaction mixture was then added in one portion to the amine (648.3 mg, 1.231 mmol). The resulting mixture was stirred overnight. The reaction mixture was diluted with ethyl acetate (100 ml) and diluted with 5% citric acid (1 × 50 ml), saturated NaHCO ₃ (1 × 50 ml), and brine (1 × 50 ml). The organic solution was dried (MgSO ₄ ), filtered and concentrated. The crude reaction was purified by MPLC (75% ethyl acetate / hexane) to give product EX-2A.

To a solution of EX-2A (281.3 mg, 0.3252 mmol) in 3.0 ml of trifluoroacetic acid (0.1 M) was added thioanisole (0.115 ml, 0.9796 mmol) at room temperature under stirring. The resulting mixture was stirred for 6 hours. The reaction mixture was concentrated under reduced pressure. The crude product was purified by polishing with ethyl ether. The light yellow powder was collected by filtration and washed with ethyl ether to give pure product 2 .

Using the procedures illustrated in Examples 1 and 2 and the accompanying Scheme 1, the following compounds can be prepared.

Example 3

Following step A and step B illustrated in Example 1, benzyl bromide was replaced with 3- (N-Boc-amino) benzyl bromide (Murakami, Y .; Hagishita, S .: Okada, T .; Kii, M .; Hashizume, H .; Yagami, T .; Fujimoto, M .; Bioorg.Med. Chem. 1999, 7, 1703-1714.), Alkylated intermediate methyl 3- [1- [3- (N-Boc -Amino) benzyl] -5-amino-2,4-dioxopyrimidinyl] acetate (EX-3A) can be prepared.

To a solution of 1 equivalent of cyclobutanone and 1 equivalent of ester EX-3A in tetrahydrofuran was added 1 equivalent of sodium cyanoborohydride and the mixture was stirred for several hours. The solvent was evaporated off to afford the crude product. The crude product was purified by silica gel chromatography to purified methyl 2- [3- [1- [3- (N-Boc-amino) benzyl] -5- (N-cyclobutyl) amino-2,4-dioxo Pyrimidinyl]]-acetate (EX-3B) was obtained.

According to the remaining procedure illustrated in Example 1, the compounds indicated in Example 3 can be obtained.

Example 4

A solution of 1 equivalent of 3-nitrophenylisocyanate and 1 equivalent of amide in DMF was heated to 100 ° C. for several hours. The solvent was evaporated off to afford the crude product. The crude product was purified by silica gel chromatography to afford the purified product 1- [3-nitrophenyl] -5-nitro-2,4-dioxopyrimidine (EX-4A).

A solution of 1 equivalent of uracil EX-4A in dimethylsulfoxide was added in one portion to 1.1 equivalents of potassium bicarbonate with stirring. After about 10 minutes a solution containing 1.1 equivalents of methyl bromoacetate in dimethylsulfoxide was added dropwise over 10 minutes. The reaction mixture was heated to 40 ° C and stirred for 18 hours. The reaction mixture was diluted with water. The aqueous solution was extracted with ethyl acetate and the combined organic solutions were washed with water and brine. The organic solution was dried over MgSO ₄ , filtered and concentrated to give crude product. The crude product was purified by silica gel chromatography to purified methyl 2- [3- [1- [3-nitrophenyl] -5-nitro-2,4-dioxopyrimidinyl]] acetate (EX-4B) Obtained.

A suspension of methyl ester EX-4B and methanol in tetrahydrofuran was added to excess lithium hydroxide in water. The reaction was stirred for 1 hour and the volatiles were removed under reduced pressure. The remaining aqueous solution was cooled in an ice bath and acidified to pH 1 with 1.0 N HCl to form a white precipitate. The precipitate was collected by filtration, washed with 1.0 N HCl and water and dried under vacuum to give the pure acid 2- [3- [1- [3-nitrophenyl] -5-nitro-2,4-dioxopyrimidy Nyl] acetic acid (EX-4C) was obtained.

A solution of acid EX-4C in dimethylformamide (0.1 M) was charged with 5 equivalents of N, N-diisopropylethylamine, 1 equivalent of N-hydroxybenzotriazole, and 1- [3- (dimethylamino) propyl]- To 1 equivalent of 3-ethylcarbodiimide hydrochloride was added. The resulting mixture was stirred for 30 minutes. Thereafter, one equivalent of 4- (N-Boc-amidino) benzylamine was added to the reaction mixture in one portion. The resulting mixture was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with 5% citric acid, saturated NaHCO ₃ and brine. The organic solution was dried (MgSO ₄ ), filtered and concentrated. Purified by MPLC to give pure, N- [4- (N-Boc-amidinobenzyl)]-2- [3- [1- [3-nitrophenyl] -5-nitro-2,4-dioxopyrimidinyl ]] Acetamide (EX-4D) was obtained.

A solution of bis-nitro compound EX-4D in methanol was treated with 5% by mole of 10% Pd / C under a hydrogen atmosphere (balloon pressure). The suspension was stirred overnight. Filtration through Celite 545 after removal of solvent gave pure water, N- [4- (N-Boc-amidinobenzyl)]-2- [3- [1- [3-aminophenyl] -5-amino-2, 4-dioxopyrimidinyl] acetamide (EX-4E) was obtained.

A solution of 1 equivalent of cyclobutanone and bis-amine EX-4E in tetrahydrofuran was treated with 1 equivalent of sodium cyanoborohydride, followed by a catalytic amount of hydrochloric acid. The reaction mixture was stirred for several hours at room temperature. The reaction was quenched with careful addition of water. The aqueous solution was extracted with ethyl acetate. The organic solution was washed with water and brine. The organic solution was dried (MgSO ₄ ), filtered and concentrated. Purification by MPLC purified pure, N- [4- (N-Boc-amidinobenzyl)]-2- [3- [1- [3-aminophenyl] -5- (N-cyclobutyl-amino) -2, 4-dioxopyrimidinyl]] acetamide (EX-4F) was obtained.

A solution of N-Boc amidine EX-4F in methanol was treated with 4 M HCl 3 equivalents in dioxane. The solution was stirred for 5 hours. The solvent was removed under vacuum and then polished with ethyl ether to give the pure product.

Various methylene analogs of pyrimidinedione in which methylene is present as a substituent for carbonyl of acetamide at the N-2 position of pyrimidinedione can be prepared using the procedure described below.

Example 5

EX-5A) A solution of 1 equivalent of 3-ethoxy-2-nitro-propenamide and 1 equivalent of phenyl isocyanate in DMF was heated to 100 ° C. for several hours. The solvent was evaporated off to afford the crude product. The crude product was purified by silica gel chromatography to give purified product EX-5A.

EX-5B) To a solution of 1 equivalent of EX-5A in dimethyl sulfoxide, 1.1 equivalents of potassium bicarbonate was added under stirring. After about 10 minutes, a solution containing 1.1 equivalents of methyl bromoacetate in dimethylsulfoxide was added dropwise over a period of 10 minutes. The reaction mixture was heated to 40 ° C and stirred for 18 hours. The reaction mixture was diluted with water. The aqueous solution was extracted with ethyl acetate and the combined organic solutions were washed with water and brine. The organic solution was dried over MgSO ₄ , filtered and concentrated to give crude product. The crude product was purified by silica gel chromatography to afford the purified product methyl 2- [3- [5-nitro-2,4-dioxo-1-phenylpyrimidyl]] acetate (EX-5B).

EX-5C) Diisobutylaluminum hydride (1.05 equiv) was added over 15 minutes to an equivalent equivalent of EX-5B in -78 ° C. cold solution in tetrahydrofuran. After stirring at −78 ° C. for 1 hour, the reaction was slowly quenched with cold methanol at −78 ° C. The mixture was slowly poured into ice cold 1 N HCl and the aqueous mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO ₄ , filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography to give the purified aldehyde product EX-5C.

EX-5D) 1.0 equivalent of aldehyde 2- [3- [5-nitro-2,4-dioxo-1-phenylpyrimidinyl]] ethanal (EX-5C) in dichloromethane, and 4- ( To a 1.0 equivalent suspension of N-Boc-amidino) benzylamine, and 1.2 equivalents of sodium triacetoxyborohydride were added to the catalytic acetic acid. The suspension quickly cleared and became homogeneous. The reaction was stirred for several hours. The solution was cooled in an ice bath and alkalized with 1.0 N NaOH. The reaction mixture was diluted with dichloromethane and washed with brine. The organic solution was dried (MgSO ₄ ), filtered and concentrated to give crude product. The crude product was purified by silica gel chromatography to give the purified product 2- [3-2- [2- [2- (4- (N-Boc-amidino) benzyl) amino] ethyl-5-nitro-2, 4-dioxo-1-phenylpyrimidine (EX-5D) was obtained.

EX-5E) A solution of 1 equivalent of EX-5D in methanol was degassed with hydrogen gas. A catalytic amount of 5% Pd / C was added to the solution, and the reaction mixture was stirred for 24 hours under a hydrogen atmosphere at room temperature. The crude reaction was filtered through a pad of Celite 545 and concentrated under reduced pressure. The crude product was purified by silica gel chromatography to give the purified product amine 2- [3-2- [2- [2- (4- (N-Boc-amidino) benzyl) amino] ethyl-5-amino- 2,4-dioxo-1-phenylpyrimidine (EX-5E) was obtained.

EX-5F) 1.0 equivalent of phenylacetaldehyde and 1.0 equivalent of EX-5E in dichloromethane and 1.2 equivalents of sodium triacetoxyborohydride were added to the catalytic acetic acid. The suspension quickly cleared and became uniform. The reaction was stirred for several hours. The solution was cooled in an ice bath and basified with 1.0 N NaOH. The reaction mixture was diluted with dichloromethane and washed with brine. The organic solution was dried (MgSO ₄ ), filtered and concentrated to give crude product. The crude product was purified by silica gel chromatography to purified 2- [3-2- [2- [2- (4- (N-Boc-amidino) benzyl) amino] ethyl-5- (N- (2 -Phenylethyl) amino) -2,4-dioxo-1-phenylpyrimidine (EX-5F) was obtained.

To an EX-5F 1 equivalent flask was added 4 M HCl in dioxane. The resulting solution was stirred overnight. The solution was concentrated and the crude product was triturated from ethyl ether to afford the purified product as dihydrochloride salt.

Sulfonyl analogs of pyrimidinedione in which sulfonyl is present at the N-2 position of pyrimidinedione as a substituent for carbonyl of acetamide can be prepared as described in specific Example 6 below.

Example 6

EX-6A) A solution of 1 equivalent of EX-5A in dimethylsulfoxide was added in one portion to 1.1 equivalents of potassium bicarbonate with stirring. After about 10 minutes, a solution containing 1.1 equivalents of sodium bromomethylsulfonate in dimethylsulfoxide was added dropwise over 10 minutes. The reaction mixture was heated to 40 ° C and stirred for 18 hours. The reaction mixture was diluted with water. The aqueous solution was extracted with ethyl acetate. The combined organic solution was washed with water and brine. The organic solution was dried over MgSO ₄ , filtered and concentrated to give crude product. The crude product was purified by silica gel chromatography to give the purified product 3- [5-nitro-2,4-dioxo-1-phenylpyrimidyl] methanesulfonic acid (EX-6A).

EX-6B) A solution of 1 equivalent of EX-6A in methanol was degassed with hydrogen gas. A catalytic amount of 5% Pd / C was added to the solution, and the reaction mixture was stirred for 24 hours under a hydrogen atmosphere at room temperature. The crude reaction was filtered through a pad of Celite 545 and concentrated under reduced pressure. The crude product was purified by silica gel chromatography to afford the purified product 3- [5-amino-2,4-dioxo-1-phenylpyrimidyl] methanesulfonic acid (EX-6B).

EX-6C) 1.0 equivalent of phenylacetaldehyde and 1.0 equivalent of EX-6B in dichloromethane and 1.2 equivalents of sodium triacetoxyborohydride were added to the catalytic acetic acid. The reaction was stirred for several hours. The solution was cooled in an ice bath and basified with 1.0 N NaOH. The reaction mixture was diluted with dichloromethane and washed with brine. The organic solution was dried (MgSO ₄ ), filtered and concentrated to give crude product. The crude product was purified by silica gel chromatography to give the purified product 3- [5- [N- (2-phenylethyl) amino] -2,4-dioxo-1-phenylpyrimidyl] methanesulfonic acid (EX- 6C) was obtained.

EX-6D) A solution of 1 equivalent of EX-6C in dichloromethane with a few drops of dimethylformamide was cooled to 0 ° C. Thionyl chloride (1.1 equiv) was added dropwise and the solution was slowly warmed to room temperature. After completion of the reaction, the volatile components were removed under reduced pressure and the sulfonyl chloride product was used immediately. Sulfonyl chloride was dissolved in dichloromethane and 1 equivalent of 4- (N-Boc-amidino) benzylamine, an appropriate amine in DMF, was added to the sulfonyl chloride solution with 5 equivalents of N-methylmorpholine. After completion of the reaction, polyaldehyde and / or polyamine resin (10 equiv) was added to remove any unreacted starting material. The resin was filtered off, rinsed with DMF / DCM (1: 1), the solvent was removed under reduced pressure, pure N- [4- (N-Boc-amidino) benzyl] -3- [5- [N- (2 -Phenylethyl) amino] -2,4-dioxo-1-phenylpyrimidyl] methanesulfonamide (EX-6D) was obtained.

One equivalent of EX-6D flask was added to 4 M HCl in dioxane. The resulting solution was stirred overnight. The solution was concentrated and the crude product was triturated from ethyl ether to afford the purified product of Example 6.

Triazinedione (aza analog) of uracil (ie pyrimidinedione) in which nitrogen is present as a substituent to carbon at the 5-position of pyrimidinedione can be prepared as described in specific example 7.

Example 7

EX-7A) A mixture of aniline ( 1 ; 50 mmol), concentrated HCl (10 ml), and water (50 ml) was cooled to 5 ° C. Separately, a solution of sodium nitrate (50 mmol) in water (7.2 ml) was cooled to 5 ° C. and added to the aniline hydrochloride slurry with an addition tube below the liquid surface. The temperature was kept at 5 ° C. during the addition and for 1 hour thereafter. This solution of diazotized aniline (EX-7A) was used in the next step.

EX-7B) A mixture of cyanoacetylurethane (59 mmol), pyridine (656 ml), ice (216 g) and water (40 ml) was added while stirring the slurry of EX-67A over 15 minutes with stirring. Was maintained. After addition time of stirring at 5 ° C., N-ethoxycarbonyl-2-cyano-2- (N-phenylhydrazo) acetamide (EX-7B) as an orange solid was isolated by filtration.

EX-7C) A mixture of EX-7B (95 mmol), sodium acetate (110 mmol) and acetic acid (140 ml) was refluxed for 75 minutes. The resulting clean solution was concentrated under reduced pressure, and the separated solid was removed by filtration and washed with water. The 6-cyano-2-phenyl-3,5-dioxo-1,2,4-triazine (EX-7C) phosphorus compound was recrystallized from 95% ethanol.

EX-7D) A mixture of compound EX-7C (50 mmol), 6N HCl (190 ml) and dioxane (500 ml) was refluxed for 12 hours. While cooling, the crystallization product 6- (2-phenyl-3,5-dioxo-1,2,4-triazinyl) carboxylic acid (EX-7D) was isolated by filtration and recrystallized from methanol-water. It was.

EX-7E) Acid EX-7D (8.4 mmol) was dissolved in dry tert-butyl alcohol (127 ml) and DPPA (9.3 mmol) and triethyl amine (9.3 mmol) was added. The solution was then refluxed for 24 hours. At this time, the solution was concentrated in vacuo. The residue was dissolved in methylene chloride (150 ml) and washed with 0.5 N citric acid (150 ml), 1 N NaHCO ₃ (150 ml) and water (150 ml). Thereafter, the methylene chloride solution was dried (sodium sulfate). Filtration and concentration gave Boc-protected compound EX-7E. The material can be purified by chromatography if necessary.

EX-7F) A solution of compound EX-7E (50 mmol) in DMF (150 ml) was treated in one portion with potassium carbonate (55 mmol) with stirring. After about 10 minutes, a solution of methyl bromoacetate (50 mmol) in DMF (100 ml) was added dropwise. The reaction mixture was heated to 40 ° C and stirred for 18 hours. Typical aqueous work up and chromatographic purification with pure methyl 2- (2-phenyl-3,5-dioxo-6- (N-Boc-amino) -1,2,4-triazinyl) acetate (EX-7F) Obtained.

EX-7G) A solution of compound EX-7F (50 mmol) was dissolved in methylene chloride (400 ml) and treated with TFA (100 ml). Thereafter, the resulting solution was stirred at room temperature for 4 hours. Concentration and polishing with ether gave the TFA salt (EX-7G) of methyl 2- (2-phenyl-3,5-dioxo-6-amino-1,2,4-triazinyl) acetate.

EX-7H) A solution of compound EX-7G and chloride (1: 1, 0.3 M) in tetrahydrofuran was treated with 1 equivalent of phenylacetaldehyde and 0.9 equivalent of triethyl amine. The solution was cooled to 0 ° C. and treated with 1 equivalent of sodium triacetoxyborohydride. After stirring for 5 minutes, the ice bath was removed and the reaction mixture was allowed to warm to room temperature and stirred there for 2 hours. The reaction was quenched by the addition of 1 N NaOH and the mixture was stirred for 5 minutes. After a typical aqueous workup, the chromatography was purified to give the pure product methyl 2- (2-phenyl-3,5-dioxo-6- (N- (2-phenylethyl) amino) -1,2,4-tria. Genyl) acetate (EX-7H) was obtained.

EX-7I) A solution of compound EX-7H (50 mmol) in THF (250 ml) was treated with LiOH (50 mmol). After the hydrolysis was complete, the volatiles were removed under reduced pressure. The remaining aqueous solution was cooled in an ice bath and acidified to pH 1 with 1.0 N HCl. The aqueous mixture was extracted with EtOAc. EtOAc solution was dried (sodium sulfate), filtered and concentrated to pure 2- (2-phenyl-3,5-dioxo-6- (N- (2-phenylethyl) amino) -1,2,4-triazinyl ) Acetic acid (EX-7I) was obtained.

EX-7J) A solution of compound EX-7I (50 mmol) in DMF (250 ml) was treated with N-hydroxybenzotriazole (60 mmol) and EDC hydrochloride (60 mmol). The mixture was stirred at rt for 30 min and treated with 4- (N-Cbz-amidinobenzyl) amine (50 mmol). The resulting mixture was stirred overnight. After a typical aqueous workup, the chromatography was purified to give the pure product N- (4-Cbz-amidinobenzyl) -2- (2-phenyl-3,5-dioxo-6- (N- (2-phenylethyl ) Amino) -1,2,4-triazinyl) acetamide (EX-7J) was obtained.

A solution of compound EX-7J (50 mmol) and 4M HCl-dioxane (100 ml) in methanol (300 ml) was degassed with hydrogen. 5% Pd (C) (0.5 g) was added and the solution stirred for 24 h under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through a pad of Celite 545 and concentrated under reduced pressure. Purification by reverse phase chromatography gave the pure product of Example 7.

Many novel compounds of the present invention can be prepared or prepared using methods in the field of synthesis and conventional techniques.

Compounds of formula (I) of the present invention having hydroxyl, thiol and amine functionalities can be converted into various derivatives. Alternatively, the derivatized compounds of formula (I) can be obtained by derivatizing one or more intermediates first during the preparation process, before modifying the derivatized intermediates to compounds of formula (I). The hydroxyl groups in the form of alcohols or phenols can be converted immediately to esters of carboxylic acids, sulfonic acids, carbamic acids, phosphonic acids and phosphoric acid. Acylation to form carboxylic esters can be carried out immediately using suitable acylation reagents such as aliphatic acid anhydrides or acid chlorides. Corresponding aryl and heteroaryl acid anhydrides and acid chlorides may also be used. This reaction is generally carried out using an amine catalyst such as pyridine in an inert solvent. Similarly, carbamic acid esters (urethanes) can be obtained by reacting hydroxyl groups with isocyanates and carbamoyl chlorides. Sulfonates, phosphonates and phosphate esters can be prepared using the corresponding acid chlorides and similar reagents. Compounds of formula (I) having one or more thiol groups present can be converted to the corresponding thioester derivatives similar to those of alcohols and phenols using the same reagents and comparable reaction conditions. Compounds of formula (I) having one or more primary or secondary amine groups present can be converted into the corresponding amide derivatives. Amides of carboxylic acids can be prepared using appropriate acid chlorides or anhydrides with reaction conditions similar to those used with alcohols and phenols. The elements of the corresponding primary or secondary amines can be prepared using carbamoyl chloride directly in the presence of isocyanates and acid scavengers such as triethylamine or pyrimidine. Sulfonamides can be prepared from the corresponding sulfonyl chlorides in the presence of aqueous sodium hydroxide or tertiary amines. Suitable procedures and methods for the preparation of such derivatives include House's Modern Synthetic Reactions, WA Benjamin, Inc., Shriner, Fuson, and Curtin, The Systematic Identification of Organic Compounds, 5th Amendment, John Wiley & Sons, and Fieser and Fieser, Reagents for Organic Synthesis, Rev. 1, John Wiley & Sons. Various reagents that can be used to derivatize the hydroxyl, thiol and amines of the compounds of formula (I) are obtainable from the above cited references or commercial sources, incorporated herein by reference.

Compounds of formula (I) of the present invention having hydroxyl, thiol and amine functionalities can be alkylated with various derivatives. Alternatively, prior to modifying the alkylated intermediate to the compound of formula I, it can be obtained by alkylating one or more intermediates first in the course of the preparation. The hydroxyl groups of the compounds of formula I can be converted into ethers immediately. Alkylation to form ethers can be carried out immediately using suitable alkylation reagents such as alkyl bromide, alkyl iodide or alkyl sulfonates. Corresponding aralkyl, heteroaralkyl, alkoxyalkyl, aralkyloxyalkyl and heteroaralkyloxyalkyl bromides, iodides and sulfonates can also be used. Such reactions generally employ inert polar solvents such as DMF, DMSO, THF and similar, comparable solvents, such as alkoxide forming reagents such as sodium hydride, potassium t-butoxide, sodium amide, lithium amide and n-butyl It is carried out using lithium. Compounds of formula (I) having one or more thiol groups present can be converted to the corresponding thioether derivatives similar to those of alcohols and phenols using the same reagents and comparable reaction conditions. Compounds of formula (I) having one or more primary, secondary or tertiary amine groups present can be converted into the corresponding secondary, tertiary or quaternary ammonium derivatives. Quaternary ammonium derivatives can be prepared using suitable bromide, iodide and sulfonates similar to those used with alcohols and phenols. Conditions include reaction of the amine by warming the alkylating reagent in stoichiometric amounts of the amine (ie, 1 equivalent of tertiary amine, 2 equivalents of secondary amine, and 3 equivalents of primary amine). With primary and secondary amines, acid scavenger 2 and 1 equivalent are used simultaneously, respectively. Secondary or tertiary amines can be prepared from the corresponding primary or secondary amines. Primary amines can be dialkylated by reductive amination with aldehydes such as formaldehyde and sodium cyanoborohydride in the presence of glacial acetic acid. Primary amines can be monoalkylated by first monoprotecting the amine with an instant cleaved protecting group such as trifluoroacetyl. Alkylating agents such as dimethylsulfate in the presence of non-nucleophilic bases such as Barton's base (2-tert-butyl-1,1,3,3-tetramethylguanidine) provide monomethylated protective amines. Removal of the protecting group with aqueous potassium hydroxide gives the desired monoalkylated amine. Additional suitable procedures and methods for preparing such derivatives are described in House's Modern Synthetic Reactions, WA Benjamin, Inc., Shriner, Fuson, and Curtin, The Systematic Identification of Organic Compounds, 5th Amendment, John Wiley & Sons, and [Fieser and Fieser, Reagents for Organic Synthesis, published by John Wiley & Sons]. Perfluoroalkyl derivatives are described in Des Martaeau, J. Chem. Soc. Chem. Commun. 2241 (1998). Various reagents that can be used to derivatize the hydroxyl, thiol and amines of the compounds of formula (I) are obtainable from the above cited references or commercial sources, incorporated herein by reference.

Assay for Biological Activity

TF-VIIa analysis

In this assay, 100 nM recombinant soluble tissue factor and 2 nM recombinant human factor VIIa were treated with 0.4 mM substrate N-methylsulfonyl-D-phe-gly-arg-p-nitroaniline, and inhibitor or buffer (5 mM CaCl ₂ , 50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA) was added to a 96-well assay plate containing. The reaction, with a final volume of 100 μl, was immediately measured at 405 nm to determine the background absorbance. Plates were incubated at room temperature for 60 minutes, at which time the hydrolysis rate of the substrate was measured by monitoring the reaction at 405 nm for the release of p-nitroaniline. Percent inhibition of TF-VIIa activity was calculated from OD _{405 nm} values from experimental and control samples.

Xa analysis

0.3 nM human factor Xa and 0.15 mM N-α-benzyloxycarbonyl-D-arginyl-L-glycyl-L-arginine-p-nitroaniline-dihydrochloride (S-2765) was inhibited or buffered (50) was added to a 96-well assay plate containing one of mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reaction, with a final volume of 100 μl, was immediately measured at 405 nm to determine the background absorbance. Plates were incubated at room temperature for 60 minutes, at which time the hydrolysis rate of the substrate was measured by monitoring the reaction at 405 nm for the release of p-nitroaniline. Percent inhibition of Xa activity was calculated from OD _{405 nm} values from experimental and control samples.

Thrombin analysis

0.28 nM human thrombin and 0.06 mM HD-phenylalanyl-L-pipecolyl-L-arginine-p-nitroaniline dihydrochloride with inhibitor or buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA ) To a 96-well assay plate containing one of The reaction, with a final volume of 100 μl, was immediately measured at 405 nm to determine the background absorbance. Plates were incubated at room temperature for 60 minutes, at which time the hydrolysis rate of the substrate was measured by monitoring the reaction at 405 nm for the release of p-nitroaniline. Percent inhibition of thrombin activity was calculated from OD _{405 nm} values from experimental and control samples.

Trypsin analysis

5 [mu] g / ml and 0.375 mM N- [alpha] -benzoyl-L-arginine-p-nitroanilide (L-BAPNA) from the swine pancreas were treated with inhibitors or buffers (50 mM Tris-HCl, pH 8.0, 100 mM). NaCl, 0.1% BSA) was added to a 96-well assay plate containing. The reaction, with a final volume of 100 μl, was immediately measured at 405 nm to determine the background absorbance. Plates were incubated at room temperature for 60 minutes, at which time the hydrolysis rate of the substrate was measured by monitoring the reaction at 405 nm for the release of p-nitroaniline. Percent inhibition of trypsin activity was calculated from OD _{405 nm} values from experimental and control samples.

Recombinant soluble TF consisting of amino acids 1-219 of the mature protein sequence was expressed in E. coli and purified using mono Q Sepharose FPLC. Recombinant human VIIa was purchased from American Diagnostica (Greenwich, Connecticut) and the staining substrate N-methylsulfonyl-D-phe-gly-arg-p-nitroaniline was obtained from American Peptide Company, Inc. (Sunnyvale, Calif.). Factor Xa was obtained from Enzyme Research Laboratories (South Bend, Indiana), thrombin from Calbiochem (La Jolla, Calif.) And trypsin and L-BAPNA from Sigma (St. Louis, Missouri). Stainable substrates S-2765 and S-2238 were purchased from Chromogenix (Sweden).

The biological activities of the compounds of Examples 1-7 as determined by the bioanalytical procedure are summarized in Table 1.

Inhibitory Activity of Uracil on Factor Xa, TF-VIIA, Thrombin II and Trypsin II Example number TF-VIIA IC50 (μM) Thrombin II IC50 (μM) Factor Xa IC50 (μM) Trypsin II IC50 (μM) One > 100 13.0 25.6 0.4 2 12.9 0.3 0.2 0.2

Claims (50)

Compounds of the formula: or pharmaceutically acceptable salts thereof [Wherein B is of the formula V: [Formula V] Wherein D ¹ , D ² , J ¹ , J ² and K ¹ are independently selected from the group consisting of C, N, O, S and covalent bonds provided that at most one is a covalent bond and D ¹ , D ^{At least one of 2} , J ¹ , J ^2, and K ¹ is O, at most one of D ¹ , D ² , J ¹ , J ^2, and K ¹ is S, D ¹ , D ² , J ¹ , J ² and If two of K ¹ are O and S, then one of D ¹ , D ² , J ¹ , J ^2, and K ¹ must be covalent, and no more than four of D ¹ , D ² , J ¹ , J ^2, and K ¹ N; R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently hydrido, acetamido, haloacetamido, amidino, guani Dino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxyalkyl, hydroxy, amino, alkoxyamino, nitro, lower alkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl, alkylsul Ponyl, alkylsulfonylalkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosul Phonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy, Carboxy, carboxamido, carboxamidoalkyl and cyano It is selected from the group consisting of; R ¹⁶ , R ¹⁹ , R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently and independently Q ^b , provided that two R ¹⁶ and R ¹⁹ are not simultaneously Q ^b and Q ^b is Q ^be ; B is optionally hydrido, trialkylsilyl, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkylenyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl and C ₂ -C ₈ halo Is selected from the group consisting of alkyl, wherein each member of the group B consists of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ at any carbon atom up to six from the point of attachment of B to A Optionally substituted with one or more of the group); B is optionally selected from the group consisting of C ₃ -C ₁₅ cycloalkyl and C ₄ -C ₉ saturated heterocyclyl, wherein each ring carbon is optionally substituted with R ³³ and a ring of the point of attachment of B to A Ring carbons other than carbon are optionally substituted with oxo, provided that at least two ring carbons are not substituted at the same time with oxo, and ring carbon and nitrogen adjacent to the carbon position at the point of attachment are optionally substituted with R ⁹ or R ¹³ , and R Ring carbon or nitrogen adjacent to position ⁹ and two atoms away from the point of attachment is optionally substituted with R ¹⁰ , ring carbon or nitrogen adjacent to position R ¹³ and two atoms away from the point of attachment is optionally substituted with R ¹² and at the point of attachment dropping three-membered ring carbon or nitrogen adjacent to the R ¹⁰ position is optionally substituted with R ^11, dropping three atoms from the point of attachment ring carbon or nitrogen adjacent to the R ¹² position is optionally substituted by R ³³ And, dropping four atoms from the point of attachment being optionally substituted by a ring carbon or nitrogen adjacent to the R ³⁴ R ¹¹ and R ³³ position); A is selected from the group consisting of a single covalent bond, (W ⁷ ) _rr- (CH (R ¹⁵ )) _pa and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr , wherein rr is 0 to 1 Is an integer selected from, pa is an integer selected from 0 to 6, W ⁷ is O, S, C (O), (R ⁷ ) NC (O), (R ⁷ ) NC (S) and N (R ⁷ ) and at least two of the groups consisting of rr and pa are not zero at the same time); R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl; R ¹⁵ is selected from the group consisting of hydrido, hydroxy, halo, alkyl and haloalkyl; ψ is selected from the group consisting of NH and NOH; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl , Alkoxyamino, thiol and alkylthio; R ² is Z ⁰ -Q; Z ⁰ is a covalent single bond, (CR ⁴¹ R ⁴² ) _q (where q is an integer selected from 1 to 3), (CH (R ⁴¹ )) _g -W ^0- (CH (R ⁴² )) _p (formula G and p are integers independently selected from 0 to 3, and W ⁰ is selected from the group consisting of O, S, C (O), S (O), N (R ⁴¹ ) and ON (R ⁴¹ ). ) And (CH (R ⁴¹ )) _e -W ^22- (CH (R ⁴² )) _h (wherein e and h are integers independently selected from 0 to 1, and W ²² is CR ⁴¹ = CR ⁴² , 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 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-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydrofuranyl Selected from the group consisting of: provided that Z ⁰ is directly bonded to the pyrazinone ring; R ⁴¹ and R ⁴² are independently selected from the group consisting of amidino, hydroxyamino, hydrido, hydroxy, amino and alkyl; Q is selected from the group consisting of hydrido (where Z ⁰ is not a covalent single bond) and formula II: [Formula II] Wherein D ¹ , D ² , J ¹ , J ² and K ¹ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond and D ¹ , D ^{At least one of 2} , J ¹ , J ^2, and K ¹ is O, at most one of D ¹ , D ² , J ¹ , J ^2, and K ¹ is S, D ¹ , D ² , J ¹ , J ² and If two of K ¹ are O and S, one of D ¹ , D ² , J ¹ , J ^2, and K ¹ must be covalent, and no more than four of D ¹ , D ² , J ¹ , J ^2, and K ¹ Is N, provided that R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are each independently selected to maintain tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur and divalent properties of oxygen, ; K is (CR ^4a R ^4b ) _n (wherein n is an integer selected from 1 to 2); R ^4a and R ^4b are independently selected from the group consisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl and haloalkyl; E ⁰ is E ¹ when K is (CR ^4a R ^4b ) _n (wherein E ¹ is a covalent single bond, C (O), C (S), C (O) N (R ⁷ ), (R ⁷ ) NC (O), S (O) ₂ , (R ⁷ ) NS (O) ₂ and S (O) ₂ N (R ⁷ ); Y ⁰ is of formula IV: [Formula IV] Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond, K ² is C, and D One or less of ⁵ , D ⁶ , J ^5, and J ⁶ is O, one or less of D ⁵ , D ⁶ , J ^5, and J ⁶ is S, and two of D ⁵ , D ⁶ , J ^5, and J ⁶ are O And when S one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be covalent, at most 4 of D ⁵ , D ⁶ , J ⁵ and J ⁶ are N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ represent hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, nitro, alkoxyamino, lower alkylamino, alkylthio, alkylsul Independently selected from the group consisting of finyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkylamino, haloalkoxyalkyl, carboalkoxy and cyano ; Q ^b is NR ²⁰ R ²¹ , aminoalkylenyl, Q ^be where Q ^be is hydrido, N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that two R ²⁰ and R ²¹ are not hydroxy, amino, alkylamino, or dialkylamino at the same time, and two R ²³ and R ²⁴ are simultaneously hydroxy, amino, alkyl Not amino or dialkylamino; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl, hydroxy, aminoalkylenyl, amino, dialkylamino, alkylamino and hydroxyalkyl Become; Q^sIs a single covalent bond, (CR³⁷R³⁸)_b(Where b is an integer selected from 1 to 4) and (CH (R¹⁴))_c-W^One-(CH (R¹⁵))_dWherein c and d are independently integers selected from 1 to 3, and W^OneIs C (O) N (R¹⁴), (R¹⁴NC (O), S (O), S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴S (O)₂And N (R¹⁴Selected from the group consisting of¹⁴ Is selected from other than halo when directly bonded to N (CR³⁷R³⁸)_bAnd (CH (R¹⁴))_cE⁰Coupled to; R ¹⁴ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl; R ³⁷ and R ³⁸ are independently selected from the group consisting of hydrido, alkyl and haloalkyl; R ³⁸ is optionally selected from the group consisting of aroyl and heteroaroyl; Y ⁰ is optionally Q ^b -Q ^ss (where Q ^ss is (CH (R ¹⁴ )) _e -W ^2- (CH (R ¹⁵ )) _h (wherein e and h are independently Is an integer selected from 1 to 2, W ² is CR ^4a = CR ^4b , provided that (CH (R ¹⁴ )) _e is bonded to E ⁰ ; Y ⁰ is optionally selected from the group consisting of Q ^b -Q ^ssss and Q ^b -Q ^ssssr , wherein Q ^ssss is (CH (R ³⁸ )) _r -W ⁵ and Q ^ssssr is (CH (R ³⁸ )) _r -W ⁶ , r is an integer selected from 1 to 2, W ⁵ and W ⁶ is 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-indene Neyl, 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, 2,7-imidazo (1,2-a) Pyridinyl, 3,4-imidazo (1,2-a) pyridinyl, 3,5-imidazo (1,2-a) pyridinyl, 3,6-imidazo (1,2-a) pyridinyl , 3,7-imidazo (1,2-a) pyridinyl, 2,4-indolyl, 2,5- Indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-iso Indolyl, 1,5-isoindoleyl, 1,6-isoindoleyl, 2,4-isoindoleyl, 2,5-isoindoleyl, 2,6-isoindoleyl, 2,7-isoindoleyl , 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl, 2,5-ben Joxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl , 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-qui Nolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolin Neyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5 Iso Nolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4, 7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3, Independently selected from the group consisting of 8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl, and W ⁵ and W attachment points other than the W ⁵ rings and W ⁶ each carbon and Hi give also contains a nitrogen source of ring ⁶ is R ^9, R ^10, R ¹¹ and optionally substituted with one or more of the group consisting of R ^12, only Q ^b is Binds to the lowest substituent number position of each W ⁵ , Q ^b binds to the highest substituent number position of each W ⁶ (CH (R ³⁸ )) _r binds to E ⁰ )]. A compound according to claim 1 or a pharmaceutically acceptable salt thereof: [Wherein B is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³² and the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³⁶ and, dropping the two atoms from the carbon of the point of attachment is optionally substituted by R ³² carbon is R ³³ is adjacent to, falling two atoms from the carbon of attachment points, and optionally substituted with carbon, R ³⁵ adjacent to the R ^36, R ³³ and R ³⁵ both Any carbon adjacent to is optionally substituted with R ³⁴ ; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydride Roxy, amino, alkoxyamino, haloalkanoyl, nitro, lower alkylamino, alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, amidosulfonyl, monoalkyl Amidosulfonyl, dialkyl amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, alkylamino, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently selected from the group consisting of; B is optionally hydrido, trialkylsilyl, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkylenyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl and C ₂ -C ₈ halo Selected from the group consisting of alkyl, wherein each member of the group B is selected from R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ at any of up to five carbon atoms from the point of attachment of B to A Optionally substituted with one or more of the group consisting of; B is optionally selected from the group consisting of C ₃ -C ₁₂ cycloalkyl and C ₄ -C ₉ saturated heterocyclyl, wherein each ring carbon is optionally substituted with R ³³ , ring carbon of the point of attachment of B to A Ring carbons except are optionally substituted with oxo, provided that two or more ring carbons are not substituted at the same time with oxo, and ring carbon and nitrogen adjacent to the carbon at the point of attachment are optionally substituted with R ⁹ or R ¹³ , and at the point of attachment Ring carbon or nitrogen two atoms apart and adjacent to position R ⁹ is optionally substituted by R ¹⁰ , ring carbon or nitrogen two atoms apart and adjacent to R ¹³ optionally substituted by R ¹² and three atoms apart from R ¹⁰ The ring carbon or nitrogen adjacent to the position is optionally substituted by R ¹¹ , three atoms away from the point of attachment and the ring carbon or nitrogen adjacent to the R ¹² position is optionally substituted by R ³³ and attached Four carbon atoms away and adjacent to the R ¹¹ and R ³³ positions are optionally substituted with R ³⁴ ; R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy, halo Alkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, arylsulfinyl, arylsulfamido, alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, Haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido and cyano; R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are selected from the group consisting of heteroaryl and heterocyclyl, provided that R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are substituents for other than B ; A is selected from the group consisting of a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1 and pa is an integer selected from 0 to 3) And W ⁷ is selected from the group consisting of O, S, C (O), (R ⁷ ) NC (O), (R ⁷ ) NC (S) and N (R ⁷ ); R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl; R ¹⁵ is selected from the group consisting of hydrido, hydroxy, halo, alkyl and haloalkyl; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol and alkyl Selected from the group consisting of thio; R ² is Z ⁰ -Q; Z ⁰ is a covalent single bond, (CR ⁴¹ R ⁴² ) _q (where q is an integer selected from 1 to 2), (CH (R ⁴¹ )) _g -W ^0- (CH (R ⁴² )) _p (formula Wherein g and p are integers independently selected from 0 to 3, and W ⁰ is selected from the group consisting of O, S and N (R ⁴¹ )) and (CH (R ⁴¹ )) _e -W ^22- (CH (R ⁴² )) _h (wherein e and h are integers independently selected from 0 to 1, and W ²² is CR ⁴¹ = CR ⁴² , 1,2-cyclopropyl, 1,2-cyclobutyl, 1, 2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 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- Selected from the group consisting of lollidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl) Provided that Z ⁰ is directly bonded to the pyrazinone ring; R ⁴¹ and R ⁴² are independently selected from the group consisting of hydrido, hydroxy and amino; Q is selected from the group consisting of hydrido (where Z ⁰ is not a covalent single bond), aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , The other carbon adjacent to the carbon of is optionally substituted with R ¹³ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ⁹ is optionally substituted with R ¹⁰ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ¹³ is Optionally substituted with ^12, and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ; K is CHR ^4a , wherein R ^4a is selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl and haloalkyl; E ⁰ is selected from the group consisting of a covalent single bond, C (O) N (H), (H) NC (O), (R ⁷ ) NS (O) ₂ and S (O) ₂ N (R ⁷ ) ; Y ⁰ is of formula IV: [Formula IV] Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at most one may be a covalent bond, and K ² is C One or less of D ⁵ , D ⁶ , J ⁵ and J ⁶ may be O, one or less of D ⁵ , D ⁶ , J ⁵ and J ⁶ may be S, D ⁵ , D ⁶ , J ⁵ and 4 or less of J ⁶ may be N, provided that R ⁹ , R ¹⁰ , R ¹¹ , R ^12, and R ¹³ each independently represent tetravalent properties of carbon, trivalent properties of nitrogen, divalent properties of sulfur, and oxygen 2 is chosen to maintain its properties; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl, Independently selected from the group consisting of alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido, N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) and C (NR ²⁵ ) NR ²³ R ²⁴ Selected from the group consisting of: provided that two R ²⁰ and R ²¹ are not hydroxy, amino, alkylamino, or dialkylamino at the same time, and two R ²³ and R ²⁴ are simultaneously hydroxy, amino, alkylamino, or di Not alkylamino; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, dialkylamino, alkylamino and dialkylamino; Q^sIs a single covalent bond, (CR³⁷R³⁸)_b(Where b is an integer selected from 1 to 4) and (CH (R¹⁴))_c-W^One-(CH (R¹⁵))_dWherein c and d are independently integers selected from 1 to 3, and W^OneIs C (O) N (R¹⁴), (R¹⁴NC (O), S (O), S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴S (O)₂And N (R¹⁴Selected from the group consisting of¹⁴ Is selected from other than halo when directly bonded to N (CR³⁷R³⁸)_bAnd (CH (R¹⁴))_cE⁰Coupled to; R ¹⁴ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl; R ³⁷ and R ³⁸ are independently selected from the group consisting of hydrido, alkyl and haloalkyl; R ³⁸ is optionally selected from the group consisting of aroyl and heteroaroyl; Y ⁰ is optionally Q ^b -Q ^ss (where Q ^ss is (CH (R ¹⁴ )) _e -W ^2- (CH (R ¹⁵ )) _h (where e and h are independently Is an integer selected from 1 to 2, W ² is CR ^4a = CR ^4b , provided that (CH (R ¹⁴ )) _e is bonded to E ⁰ )]. A compound according to claim 2 or a pharmaceutically acceptable salt thereof, characterized by: B consists of hydrido, trialkylsilyl, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkylenyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl and C ₂ -C ₈ haloalkyl Wherein each circle of group B is selected from the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ at any carbon atom up to six from the point of attachment of B to A Optionally substituted with one or more; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkyl Group consisting of thio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently from; A is (CH (R ¹⁵ )) _pa -W ⁷ wherein pa is an integer selected from 1 to 3, and W ⁷ is selected from the group consisting of O, S and N (R ⁷ ), wherein R ⁷ is selected from the group consisting of hydrido and alkyl); R ¹⁵ is selected from the group consisting of hydrido, hydroxy, halo, alkyl and haloalkyl, provided that when R ¹⁵ is on a carbon atom directly bonded to W ⁷ , R ¹⁵ is other than hydroxy and halo ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol and alkyl Selected from the group consisting of thio; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of a covalent single bond and (CR ⁴¹ R ⁴² ) _q , wherein q is an integer selected from 1 to 2; R ⁴¹ and R ⁴² are independently selected from the group consisting of hydrido, hydroxy and amino; Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , and the point of attachment Two atoms away from carbon at and adjacent to R ⁹ are optionally substituted with R ¹⁰ , two atoms away from carbon at the point of attachment and carbon adjacent to R ¹³ are optionally substituted with R ¹² and any adjacent to both R ¹⁰ and R ¹² Carbon is optionally substituted with R ¹¹ ; R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy, halo Alkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfamido, alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, Haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido and cyano; K is CHR ^4a , wherein R ^4a is selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl and haloalkyl; E ⁰ is selected from the group consisting of a covalent single bond, C (O) N (H), (H) NC (O), (R ⁷ ) NS (O) ₂ and S (O) ₂ N (R ⁷ ) ; Y ⁰ is of formula IV: [Formula IV] Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond, K ² is C, and D One or less of ⁵ , D ⁶ , J ^5, and J ⁶ is O, one or less of D ⁵ , D ⁶ , J ^5, and J ⁶ is S, and two of D ⁵ , D ⁶ , J ^5, and J ⁶ are O And when S one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be covalent, and no more than four of D ⁵ , D ⁶ , J ⁵ and J ⁶ are N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl, Independently selected from the group consisting of alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkylamino and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido, N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) and C (NR ²⁵ ) NR ²³ R ²⁴ Selected from the group consisting of: provided that two R ²⁰ and R ²¹ are not hydroxy, amino, alkylamino, or dialkylamino at the same time, and two R ²³ and R ²⁴ are simultaneously hydroxy, amino, alkylamino, or di Not alkylamino; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino; Q^sIs a single covalent bond, (CR³⁷R³⁸)_b(Where b is an integer selected from 1 to 3) and (CH (R¹⁴))_c-W^One-(CH (R¹⁵))_dWherein c and d are independently integers selected from 1 to 2, and W^OneIs C (O) N (R¹⁴), (R¹⁴NC (O), S (O), S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴S (O)₂And N (R¹⁴Selected from the group consisting of¹⁴ Is selected from other than halo when directly bonded to N (CR³⁷R³⁸)_bAnd (CH (R¹⁴))_cE⁰Coupled to; R ¹⁴ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl; R ³⁷ and R ³⁸ are independently selected from the group consisting of hydrido, alkyl and haloalkyl; R ³⁸ is optionally selected from the group consisting of aroyl and heteroaroyl; Y ⁰ is optionally Q ^b -Q ^ss (where Q ^ss is (CH (R ¹⁴ )) _e -W ^2- (CH (R ¹⁵ )) _h (where e and h are independently Is an integer selected from 1 to 2, W ² is CR ^4a = CH, provided that (CH (R ¹⁴ )) _e is bonded to E ⁰ ). A compound according to claim 3, or a pharmaceutically acceptable salt thereof: [Wherein B is hydrido, trialkylsilyl, C ₂ -C ₄ alkyl, C ₃ -C ₅ alkylenyl, C ₃ -C ₄ alkenyl, C ₃ -C ₄ alkynyl and C ₂ -C ₄ Selected from the group consisting of haloalkyl, wherein each member of the group B is one or more of the group consisting of R ³² , R ³³ and R ³⁴ at any up to three carbon atoms from the point of attachment of B to A Optionally substituted with; R ³² , R ³³ and R ³⁴ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, Independently selected from the group consisting of monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido and cyano; A is (CH (R ¹⁵ )) _pa -N (R ⁷ ) wherein pa is an integer selected from 1 to 2 and R ⁷ is selected from the group consisting of hydrido and alkyl; R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds and CH ₂ ; Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , and the point of attachment Two atoms away from carbon of and adjacent to R ⁹ are optionally substituted by R ¹⁰ , and two atoms away from carbon of the point of attachment and carbon adjacent to R ¹³ are optionally substituted by R ¹² and any adjacent to both R ¹⁰ and R ¹² Carbon is optionally substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, mono Independently selected from the group consisting of alkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano; R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl Independently monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl and cyano; Y ⁰ is of formula IV: [Formula IV] Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond, K ² is C, and D One or less of ⁵ , D ⁶ , J ^5, and J ⁶ is O, one or less of D ⁵ , D ⁶ , J ^5, and J ⁶ is S, and two of D ⁵ , D ⁶ , J ^5, and J ⁶ are O And when S one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be covalent, and no more than four of D ⁵ , D ⁶ , J ⁵ and J ⁶ are N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido, C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) Selected from the group consisting of: provided that two R ²⁰ and R ²¹ are not hydroxy at the same time and two R ²³ and R ²⁴ are not hydroxy at the same time; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl and hydroxy; Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ ]. A compound according to claim 4, or a pharmaceutically acceptable salt thereof, characterized in that B is ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, trimethylene, tetramethylene, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl, Isobutyl, 2-methylpropenyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl and 2,2-difluoropropyl, wherein group B Each circle of is optionally substituted with one or more of the group consisting of R ³² , R ³³ and R ³⁴ at any up to 3 carbon atoms from the point of attachment of B to A; R ³² , R ³³ and R ³⁴ are hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetami Figure, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro Roethyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, Hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methyl Independently selected from the group consisting of amidocarbonyl, N, N-dimethylamidocarbonyl and cyano; A is selected from the group consisting of a single covalent bond, NH and N (CH ₃ ); M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2 , 2-tetrafluoroethoxy, fluoro, chloro and bromo; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds and CH ₂ ; Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4 -Pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyri Midinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl and 1,3,5-triazin-2-yl, wherein one carbon adjacent the carbon at the point of attachment Is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ⁹ is optionally substituted with R ¹⁰ , from the carbon at the point of attachment Two atoms apart and adjacent to R ¹³ are optionally substituted with R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N -Methylamino, N, N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2 , 3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N- Methyl amidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl , N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and cyano are independently selected from the group consisting of; R ¹⁰ and R ¹² represent hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, meth Methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amido Dosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl Independently selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro, chloro, bromo and cyano Become; Y ⁰ is selected from the group consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 2-Q ^b -4-Q ^s -3-R ¹⁶ -6-R ¹⁸ pyrazine, 3-Q ^b -6-Q ^s -2-R ¹⁸ -5-R ¹⁸ -4-R ¹⁹ pyridazine, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ pyrimidine, 5-Q ^b -2-Q ^s -3-R ¹⁶ -6-R ¹⁹ pyrimidine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ furan, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ furan, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ pyrrole, 2-Q ^b -Q ^s -3-R ¹⁶ -4-R ¹⁷ pyrrole, 4-Q ^b -2-Q ^s- 5-R ¹⁹ imidazole, 2-Q ^b -4-Q ^s- 5-R ¹⁷ imidazole, 3-Q ^b -5-Q ^s -4-R ¹⁶ isoxazole, 5-Q ^b -3-Q ^s -4-R ¹⁶ isoxazole, 2-Q ^b -5-Q ^s -4-R ¹⁶ pyrazole, 4-Q ^b -2-Q ^s- 5-R ¹⁹ thiazole, and 2-Q ^b -5-Q ^s -4-R ¹⁷ thiazole; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, Amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsul Finyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy , 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydride Independently selected from the group consisting of hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido, C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) Provided that any two of the group consisting of R ²⁰ , R ²¹ , R ²³ and R ²⁴ are bonded to the same atom, one or less of R ²⁰ , R ²¹ , R ²³ and R ²⁴ Oxy, wherein the Q ^b group is bonded directly to a carbon atom; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl and hydroxy; Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ . The compound of claim 4, wherein the compound of formula [Wherein A is selected from the group consisting of CH ₂ N (CH ₃ ), CH ₂ N (CH ₂ CH ₃ ), CH ₂ CH ₂ N (CH ₃ ) and CH ₂ CH ₂ N (CH ₂ CH ₃ ) Become; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2 , 2-tetrafluoroethoxy, fluoro, chloro and bromo; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds and CH ₂ ; Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4 -Pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyri Midinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl and 1,3,5-triazin-2-yl, wherein one carbon adjacent the carbon at the point of attachment Is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ⁹ is optionally substituted with R ¹⁰ , from the carbon at the point of attachment Two atoms apart and adjacent to R ¹³ are optionally substituted with R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N -Methylamino, N, N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2 , 3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N- Methyl amidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl , N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and cyano are independently selected from the group consisting of; R ¹⁰ and R ¹² represent hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, meth Methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amido Dosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl Independently selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro, chloro, bromo and cyano Become; Y ⁰ is selected from the group of formula consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 2-Q ^b -4-Q ^s -3-R ¹⁶ -6-R ¹⁸ pyrazine, 3-Q ^b -6-Q ^s -2-R ¹⁸ -5-R ¹⁸ -4-R ¹⁹ pyridazine, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ pyrimidine, 5-Q ^b -2-Q ^s -3-R ¹⁶ -6-R ¹⁹ pyrimidine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ furan, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ furan, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ pyrrole, 2-Q ^b -Q ^s -3-R ¹⁶ -4-R ¹⁷ pyrrole, 4-Q ^b -2-Q ^s- 5-R ¹⁹ imidazole, 2-Q ^b -4-Q ^s- 5-R ¹⁷ imidazole, 3-Q ^b -5-Q ^s -4-R ¹⁶ isoxazole, 5-Q ^b -3-Q ^s -4-R ¹⁶ isoxazole, 2-Q ^b -5-Q ^s -4-R ¹⁶ pyrazole, 4-Q ^b -2-Q ^s- 5-R ¹⁹ thiazole, and 2-Q ^b -5-Q ^s -4-R ¹⁷ thiazole; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, isopropyl, propyl, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, Aminomethyl, 1-aminoethyl, 2-aminoethyl, NN-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, Methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy, 1 , 1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl , 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl and cyano are independently selected from the group consisting of; Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ), provided that R ²⁰ , R ^When any two of the group consisting of ²¹ , R ²³ and R ²⁴ are bonded to the same atom, at most one of R ²⁰ , R ²¹ , R ²³ and R ²⁴ may be hydroxy and the Q ^b group is directly at the carbon atom Combined; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl and hydroxy; Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ ]. A compound according to claim 6, or a pharmaceutically acceptable salt thereof, characterized in that A is selected from the group consisting of CH ₂ N (CH ₃ ), CH ₂ N (CH ₂ CH ₃ ), CH ₂ CH ₂ N (CH ₃ ) and CH ₂ CH ₂ N (CH ₂ CH ₃ ); M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, tri Fluoromethoxy, fluoro and chloro; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds and CH ₂ ; Q is 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidino Phenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-carboxy-5-aminophenyl , 3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methane Sulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3- Methylphenyl, 4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thi Enyl and 3-thienyl; Y ⁰ is selected from the group of formula consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene and 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene; R ¹⁶ and R ¹⁹ are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; R ¹⁷ and R ¹⁸ are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy and cyano; Q ^b is selected from the group consisting of Q ^be wherein Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and methyl; Q ^s is CH ₂ . 8. A compound according to claim 7, or a pharmaceutically acceptable salt thereof, selected from the group consisting of: 2- [3- [1- [3-aminophenyl] -N-[[4-iminomethylphenyl] methyl] -5- [N, N-dimethylhydrazino] -2,4-dioxo-2 (2H , 4H) -pyrimidinyl]] acetamide; 2- [3- [1- [3-aminophenyl] -5- [N-ethyl-N-methylhydrazino] -N-[[4-iminomethylphenyl] methyl] -2,4-dioxo-2 (2H, 4H) -pyrimidinyl]] acetamide; 2- [3- [1- [3-aminophenyl] -6-fluoro-5- [N, N-diethylhydrazino] -N-[[4-iminomethylphenyl] methyl] -2,4- Dioxo-2 (2H, 4H) -pyrimidinyl]] acetamide; 2- [3- [1- [3-aminophenyl] -5- [N- (azetidin-1-yl) amino] -N-[[4-iminomethylphenyl] methyl] -2,4-dioxo -2 (2H, 4H) -pyrimidinyl]] acetamide; 2- [4- [2- [3-aminophenyl] -N-[[4-iminomethylphenyl] methyl] -6- [N, N-dimethylhydrazino] -3,5-dioxo-2 (3H , 5H) -1,2,4-triazinyl]] acetamide; 2- [4- [2- [3-aminophenyl] -6- [N-ethyl-N-methylhydrazino] -N-[[4-iminomethylphenyl] methyl] -3,5-dioxo-2 (3H, 5H) -1, 2, 4-triazinyl]] acetamide; 2- [4- [2- [3-aminophenyl] -6- [N, N-diethylhydrazino] -N-[[4-iminomethylphenyl] methyl] -3,5-dioxo-2 ( 3H, 5H) -1,2,4-triazinyl]] acetamide; 2- [4- [2- [3-aminophenyl] -6- [N- (azetidin-1-yl) amino] -N-[[4-iminomethylphenyl] methyl] -3,5-dioxo -2 (3H, 5H) -1,2,4-triazinyl]] acetamide. A compound according to claim 2 or a pharmaceutically acceptable salt thereof: [Wherein B is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³² and the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³⁶ and, dropping the two atoms from the carbon of the point of attachment is optionally substituted by R ³² carbon is R ³³ is adjacent to, falling two atoms from the carbon of attachment points, and optionally substituted with carbon, R ³⁵ adjacent to the R ^36, R ³³ and R ³⁵ both Any carbon adjacent to is optionally substituted with R ³⁴ ; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkyl Group consisting of thio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently from; A is selected from the group consisting of a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1 and pa is an integer selected from 0 to 3) And W ⁷ is selected from the group consisting of (R ⁷ ) NC (O) and N (R ⁷ ); R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl; R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds, O, S, NH and CH ₂ ; Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , and the point of attachment Two atoms away from carbon of and adjacent to R ⁹ are optionally substituted by R ¹⁰ , and two atoms away from carbon of the point of attachment and carbon adjacent to R ¹³ are optionally substituted by R ¹² and any adjacent to both R ¹⁰ and R ¹² Carbon is optionally substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, mono Independently selected from the group consisting of alkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano; R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl Independently monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl and cyano; Y ⁰ is of formula IV: [Formula IV] Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond, K ² is C, and D One or less of ⁵ , D ⁶ , J ^5, and J ⁶ is O, one or less of D ⁵ , D ⁶ , J ^5, and J ⁶ is S, and two of D ⁵ , D ⁶ , J ^5, and J ⁶ are O And when S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and up to four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that both R ²⁰ and R ²¹ are hydroxy No two R ²³ and R ²⁴ are hydroxy at the same time; R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, alkyl and hydroxy; Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ ]. A compound according to claim 9, or a pharmaceutically acceptable salt thereof, characterized in that B is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4 -Pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyri Midinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl and 1,3,5-triazin-2-yl, wherein one carbon adjacent the carbon at the point of attachment is optionally substituted with R ^32, and another carbon adjacent to the carbon of attachment points is optionally substituted by R ^36, dropping the two atoms from the carbon of the point of attachment is optionally substituted with carbon, R ³³ is adjacent to R ^32, from the carbon of attachment points two drops atom and optionally substituted by R ³⁵ is a carbon adjacent to R ^36, any carbon adjacent to both R ³³ and R ³⁵ is optionally substituted with R ^34; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, Ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2, 2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo , Amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxy independent of the hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amido carbonyl, N- methyl amido-carbonyl, N, N- dimethyl-amido-carbonyl, cyano, and the group consisting of Q ^b Is selected; A is a single covalent bond, NH, N (CH ₃ ), N (OH), CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), N (CH ₃ ) C (O), C (O) NH , C (O) N (CH ₃ ), CH ₂ CH ₂ , CH ₂ CH ₂ CH ₂ , CH ₃ CHCH ₂ and CF ₃ CHCH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2 , 2-tetrafluoroethoxy, fluoro, chloro and bromo; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds, O, S, NH and CH ₂ ; Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4 -Pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyri Midinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl and 1,3,5-triazin-2-yl, wherein one carbon adjacent the carbon at the point of attachment Is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ⁹ is optionally substituted with R ¹⁰ , from the carbon at the point of attachment Two atoms apart and adjacent to R ¹³ are optionally substituted with R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N -Methylamino, N, N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2 , 3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N- Methyl amidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl , N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and cyano are independently selected from the group consisting of; R ¹⁰ and R ¹² represent hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, meth Methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amido Dosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl Independently selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro, chloro, bromo and cyano Become; Y ⁰ is selected from the group consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 2-Q ^b -4-Q ^s -3-R ¹⁶ -6-R ¹⁸ pyrazine, 3-Q ^b -6-Q ^s -2-R ¹⁸ -5-R ¹⁸ -4-R ¹⁹ pyridazine, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ pyrimidine, 5-Q ^b -2-Q ^s -3-R ¹⁶ -6-R ¹⁹ pyrimidine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ furan, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ furan, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ pyrrole, 2-Q ^b -Q ^s -3-R ¹⁶ -4-R ¹⁷ pyrrole, 4-Q ^b -2-Q ^s- 5-R ¹⁹ imidazole, 2-Q ^b -4-Q ^s- 5-R ¹⁷ imidazole, 3-Q ^b -5-Q ^s -4-R ¹⁶ isoxazole, 5-Q ^b -3-Q ^s -4-R ¹⁶ isoxazole, 2-Q ^b -5-Q ^s -4-R ¹⁶ pyrazole, 4-Q ^b -2-Q ^s- 5-R ¹⁹ thiazole, and 2-Q ^b -5-Q ^s -4-R ¹⁷ thiazole; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, Amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsul Finyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy , 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydride Independently selected from the group consisting of hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is selected from the group consisting of Q ^be where Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that two R ²³ and R ²⁴ are not hydroxy simultaneously; R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, methyl, ethyl and hydroxy; Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ . A compound according to claim 10, or a pharmaceutically acceptable salt thereof, characterized in that B is 2-aminophenyl, 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-chlorophenyl, 4-chlorophenyl, 3 , 4-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 3,4-difluorophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3-methoxyaminophenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoromethylphenyl, 2-imidazolyl, 2-pyridyl, 3-pyridyl, 5-chloro-3-trifluoro Methyl-2-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl and 3-trifluoromethyl-2-pyridyl; A is selected from the group consisting of CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, tri Fluoromethoxy, fluoro and chloro; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds, O, S, NH and CH ₂ ; Q is 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidino Phenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl, 3-carboxy-5-hydroxyphenyl , 3-carboxymethyl-5-aminophenyl, 3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl, 2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-meth Methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl, 3-triple Oromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2- Thienyl and 3-thienyl; Y ⁰ is selected from the group of formula consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene and 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene; R ¹⁶ and R ¹⁹ are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; R ¹⁷ and R ¹⁸ are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy and cyano; Q ^b is selected from the group consisting of Q ^be wherein Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and methyl; Q ^s is CH ₂ . The compound of claim 9, wherein the compound of formula [Wherein B is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³² and the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³⁶ and, dropping the two atoms from the carbon of the point of attachment is optionally substituted by R ³² carbon is R ³³ is adjacent to, falling two atoms from the carbon of attachment points, and optionally substituted with carbon, R ³⁵ adjacent to the R ^36, R ³³ and R ³⁵ both Any carbon adjacent to is optionally substituted with R ³⁴ ; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkyl Group consisting of thio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently from; A is selected from the group consisting of a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1 and pa is an integer selected from 0 to 3) And W ⁷ is N (R ⁷ ); R ⁷ is selected from the group consisting of hydrido and alkyl; R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of; R ² is Z ⁰ -Q; Z ⁰ is a covalent single bond; Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , and the point of attachment Two atoms away from carbon of and adjacent to R ⁹ are optionally substituted by R ¹⁰ , and two atoms away from carbon of the point of attachment and carbon adjacent to R ¹³ are optionally substituted by R ¹² and any adjacent to both R ¹⁰ and R ¹² Carbon is optionally substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkyl amidosul Independently selected from the group consisting of ponyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano; R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino, alkylsulfonamido, Independently selected from the group consisting of amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl and cyano ; Y ⁰ is of formula IV: [Formula IV] Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond, K ² is C, and D One or less of ⁵ , D ⁶ , J ^5, and J ⁶ is O, one or less of D ⁵ , D ⁶ , J ^5, and J ⁶ is S, and two of D ⁵ , D ⁶ , J ^5, and J ⁶ are O And when S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and up to four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and alkyl; Q ^s is CH ₂ ]. 13. A compound according to claim 12, or a pharmaceutically acceptable salt thereof, characterized in that: B is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4 -Pyrazolyl, 2-thiazolyl, 3-isoxazolyl and 5-isoxazolyl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³² and carbon at the point of attachment and the other carbon is optionally substituted with R ³⁶ adjacent to, falling two atoms from the carbon of the point of attachment is optionally substituted by R ³² carbon is R ³³ is adjacent to, falling two atoms from the carbon of attachment point on the carbon adjacent to R ³⁶ is as R ³⁵ Optionally substituted, and any carbon adjacent to both R ³³ and R ³⁵ is optionally substituted with R ³⁴ ; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methyl Thio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amido Independently selected from the group consisting of docarbonyl, carboxy, cyano and Q ^b ; A is selected from the group consisting of a single covalent bond, NH, N (CH ₃ ), CH ₂ , CH ₃ CH and CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, tri Fluoromethoxy, fluoro and chloro; R ² is selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl and 3-pyridyl Wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ and is two carbons apart from the carbon at the point of attachment and adjacent to R ⁹ Is optionally substituted by R ¹⁰ , two atoms away from the carbon at the point of attachment and carbon adjacent to R ¹³ is optionally substituted by R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted by R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N, N-dimethylamino, methylthio, trifluoromethyl, pentafluoro Roethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxy Independently selected from the group consisting of ethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy and cyano; R ¹⁰ and R ¹² represent hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxy Hydroxyethyl, 2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl Independently selected from the group consisting of, N-methylamino, dimethylamino, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo and cyano Become; Y ⁰ is selected from the group consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ pyridine, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene, ^{3-Q b -6-Q s} -2-R 16 -5-R 18 -4-R 19 ^{pyridine, 3-Q b -5-Q} s -4-R 16 -2-R 19 thiophene, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ furan, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ furan, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ pyrrole, 2-Q ^b -Q ^s -3-R ¹⁶ -4-R ¹⁷ pyrrole, 4-Q ^b- 2-Q ^s- 5-R ¹⁹ thiazole and 2-Q ^b- 5-Q ^s- 4-R ¹⁷ thiazole; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N- Methylamino, dimethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluorome Independently selected from the group consisting of oxy, fluoro, chloro, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, carboxy and cyano; Q ^b is selected from the group consisting of NR ²⁰ R ²¹ and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that the Q ^b group is bonded directly to a carbon atom; R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, methyl and ethyl; Q ^s is CH ₂ . The compound of claim 13, or a pharmaceutically acceptable salt thereof, characterized in that B is 2-aminophenyl, 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-chlorophenyl, 4-chlorophenyl, 3 , 4-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 3,4-difluorophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3-methoxyaminophenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoromethylphenyl, 2-imidazolyl, 2-pyridyl, 3-pyridyl, 5-chloro-3-trifluoro Methyl-2-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl and 3-trifluoromethyl-2-pyridyl; A is selected from the group consisting of CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is selected from the group consisting of hydrido, hydroxy, amino, methyl, trifluoromethyl, fluoro and chloro; R ² is 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amimi Dinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl, 3-carboxy-5-hydroxy Phenyl, 3-carboxymethyl-5-aminophenyl, 3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-meth Methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoroacet Amidophenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl and 3-thienyl is selected from the group consisting of; Y ⁰ is selected from the group of formula consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene and 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene; R ¹⁶ and R ¹⁹ are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; R ¹⁷ and R ¹⁸ are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy and cyano; Q ^b is selected from the group consisting of Q ^be wherein Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and methyl; Q ^s is CH ₂ . The compound of claim 14, or a pharmaceutically acceptable salt thereof, characterized in that B is 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 4-methylphenyl, phenyl, 2- Imidazolyl, 3-pyridyl, 4-pyridyl and 3-trifluoromethyl-2-pyridyl; A is selected from the group consisting of CH ₂ , NHC (O), CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is selected from the group consisting of hydrido, fluoro and chloro; R ² is 3-aminophenyl, benzyl, 3-chlorophenyl, 3-dimethylaminophenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, phenyl , 3-trifluoroacetamidophenyl, 3-bromo-2-thienyl, 2-thienyl and 3-thienyl; Y ⁰ is selected from the group consisting of 5-amidino-2-thienylmethyl, 4-amidinobenzyl, 2-fluoro-4-amidinobenzyl and 3-fluoro-4-amidinobenzyl. A compound according to claim 9, or a pharmaceutically acceptable salt thereof, selected from the group having the formula: [In the meal, R ² is 3-aminophenyl, B is 3-chlorophenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is phenyl, B is 3-chlorophenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 2-imidazolyl, A is CH ₂ CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-dimethylaminophenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 2-methylphenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is phenyl, B is 3-aminophenyl, A is C (O) NH, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is phenyl, B is 3-amidinophenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3- (N-methylamino) phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-thienyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-methylsulfonylamidophenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is phenyl, B is 4-amidinophenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-methylaminophenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is phenyl, B is phenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is phenyl, B is 4-pyridyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is phenyl, B is 3-pyridyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-chlorophenyl, B is 4-pyridyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-methylphenyl, B is 4-phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-thienyl, B is 3-chlorophenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 3-chlorophenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is phenyl, B is 3-chlorophenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is 2-imidazolyl, A is CH ₂ CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-dimethylaminophenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 2-methylphenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is phenyl, B is 3-aminophenyl, A is C (O) NH, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is phenyl, B is 3-amidinophenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3- (N-methylamino) phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-thienyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-methylsulfonylamidophenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is phenyl, B is 4-amidinophenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-methylaminophenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is phenyl, B is phenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is phenyl, B is 4-pyridyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is phenyl, B is 3-pyridyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-chlorophenyl, B is 4-pyridyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-methylphenyl, B is 4-phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-thienyl, B is 3-chlorophenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is 3-chlorophenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is phenyl, B is 3-chlorophenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 2-imidazolyl, A is CH ₂ CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-dimethylaminophenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 2-methylphenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is phenyl, B is 3-aminophenyl, A is C (O) NH, Y ⁰ is 4-amidinobenzyl and M is N; R ² is phenyl, B is 3-amidinophenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3- (N-methylamino) phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-thienyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-methylsulfonylamidophenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is phenyl, B is 4-amidinophenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-methylaminophenyl, B is phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is phenyl, B is phenyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is phenyl, B is 4-pyridyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is phenyl, B is 3-pyridyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-chlorophenyl, B is 4-pyridyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-methylphenyl, B is 4-phenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-thienyl, B is 3-chlorophenyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N]. A compound according to claim 2 or a pharmaceutically acceptable salt thereof: [Wherein B is selected from the group consisting of hydrido, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl and C ₂ -C ₈ haloalkyl, wherein B Each circle of the group is optionally substituted with one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ at any up to 6 carbon atoms from the point of attachment of B to A; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkyl Group consisting of thio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently from; A is selected from the group consisting of a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1 and pa is an integer selected from 0 to 3) And W ⁷ is selected from the group consisting of (R ⁷ ) NC (O) and N (R ⁷ ); R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl; R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds, O, S, NH and CH ₂ ; Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , and the point of attachment Two atoms away from carbon of and adjacent to R ⁹ are optionally substituted by R ¹⁰ , and two atoms away from carbon of the point of attachment and carbon adjacent to R ¹³ are optionally substituted by R ¹² and any adjacent to both R ¹⁰ and R ¹² Carbon is optionally substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, mono Independently selected from the group consisting of alkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano; R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetoamido, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl Independently monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl and cyano; Y ⁰ is of formula IV: [Formula IV] Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond, K ² is C, and D One or less of ⁵ , D ⁶ , J ^5, and J ⁶ is O, one or less of D ⁵ , D ⁶ , J ^5, and J ⁶ is S, and two of D ⁵ , D ⁶ , J ^5, and J ⁶ are O And when S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and up to four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido, C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) Selected from the group consisting of: provided that two R ²⁰ and R ²¹ are not hydroxy at the same time and two R ²³ and R ²⁴ are not hydroxy at the same time; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl and hydroxy; Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ ]. A compound according to claim 17, or a pharmaceutically acceptable salt thereof, characterized in that B is hydrido, ethyl, 2-propynyl, 2-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl , 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl, 1 -Methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3- Butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4 -Hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl- 4-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2 -Propenyl, 1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptinyl, 3-hep Tinyl, 4-heptinyl, 5-heptinyl, 2-heptyl, 1-methyl-2-hex Neyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-5-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl -4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl, 1-ethyl- 2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoro Pentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl and 3,3,3-trifluoropropyl, wherein each member of the B group is Optionally substituted with at least 5 carbon atoms from the point of attachment of B to A at least one of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ ; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, Ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2, 2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo , Amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxy independent of the hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amido carbonyl, N- methyl amido-carbonyl, N, N- dimethyl-amido-carbonyl, cyano, and the group consisting of Q ^b Is selected; A is a single covalent bond, NH, N (CH ₃ ), N (OH), CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), N (CH ₃ ) C (O), C (O) NH , C (O) N (CH ₃ ), CH ₂ CH ₂ , CH ₂ CH ₂ CH ₂ , CH ₃ CHCH ₂ and CF ₃ CHCH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2 , 2-tetrafluoroethoxy, fluoro, chloro and bromo; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of a single covalent bond, O, S, NH and CH ₂ ; Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4 -Pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyri Midinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl and 1,3,5-triazin-2-yl, wherein one carbon adjacent the carbon at the point of attachment Is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ⁹ is optionally substituted with R ¹⁰ , from the carbon at the point of attachment Two atoms apart and adjacent to R ¹³ are optionally substituted with R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N -Methylamino, N, N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2 , 3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N- Methyl amidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl , N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and cyano are independently selected from the group consisting of; R ¹⁰ and R ¹² represent hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, meth Methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amido Dosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl Independently selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro, chloro, bromo and cyano Become; Y ⁰ is selected from the group consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 2-Q ^b -4-Q ^s -3-R ¹⁶ -6-R ¹⁸ pyrazine, 3-Q ^b -6-Q ^s -2-R ¹⁸ -5-R ¹⁸ -4-R ¹⁹ pyridazine, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ pyrimidine, 5-Q ^b -2-Q ^s -3-R ¹⁶ -6-R ¹⁹ pyrimidine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ furan, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ furan, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ pyrrole, 2-Q ^b -Q ^s -3-R ¹⁶ -4-R ¹⁷ pyrrole, 4-Q ^b -2-Q ^s- 5-R ¹⁹ imidazole, 2-Q ^b -4-Q ^s- 5-R ¹⁷ imidazole, 3-Q ^b -5-Q ^s -4-R ¹⁶ isoxazole, 5-Q ^b -3-Q ^s -4-R ¹⁶ isoxazole, 2-Q ^b -5-Q ^s -4-R ¹⁶ pyrazole, 4-Q ^b -2-Q ^s- 5-R ¹⁹ thiazole, and 2-Q ^b -5-Q ^s -4-R ¹⁷ thiazole; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, Amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsul Finyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy , 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydride Independently selected from the group consisting of hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido, C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) Selected from the group consisting of: provided that two R ²⁰ and R ²¹ are not hydroxy at the same time and two R ²³ and R ²⁴ are not hydroxy at the same time; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl and hydroxy; Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ . A compound according to claim 18, or a pharmaceutically acceptable salt thereof, characterized in that B is hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R) -2-butyl, (S) -2-butyl, tert-butyl, iso Butyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl, 3- Methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxy Hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl, 2- Dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S) -2-methylbutyl, 3-aminopropyl, 2-hexyl and 4-aminobutyl; A is selected from the group consisting of a single covalent bond, CH ₂ , NHC (O), CH ₂ CH ₂ , CH ₂ CH ₂ CH ₂ and CH ₃ CHCH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, tri Fluoromethoxy, fluoro and chloro; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of a single covalent bond, O. S, NH and CH ₂ ; Q is 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidino Phenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl, 3-carboxy-5-hydroxyphenyl , 3-carboxymethyl-5-aminophenyl, 3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl, 2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-meth Methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl, 3-triple Oromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2- Thienyl and 3-thienyl; Y ⁰ is selected from the group consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene and 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene; R ¹⁶ and R ¹⁹ are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; R ¹⁷ and R ¹⁸ are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy and cyano; Q ^b is selected from the group consisting of Q ^be wherein Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and methyl; Q ^s is CH ₂ . 18. A compound of claim 17 or a pharmaceutically acceptable salt thereof: [Wherein B is selected from the group consisting of hydrido, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl and C ₂ -C ₈ haloalkyl, wherein B Each circle of the group is optionally substituted with one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ at any up to 6 carbon atoms from the point of attachment of B to A; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkyl Group consisting of thio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently from; A is selected from the group consisting of a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1 and pa is an integer selected from 0 to 3) And W ⁷ is N (R ⁷ ); R ⁷ is selected from the group consisting of hydrido and alkyl; R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of; R ² is Z ⁰ -Q; Z ⁰ is a covalent single bond; Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , and the point of attachment Carbon two atoms away from carbon and adjacent to R ⁹ is optionally substituted with R ¹⁰ , and carbon two atoms away from carbon at the point of attachment and adjacent to R ¹³ is optionally substituted with R ¹² and any adjacent to both R ¹⁰ and R ¹² Carbon is optionally substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkyl amidosul Independently selected from the group consisting of ponyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano; R ¹⁰ and R ¹² represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino, alkylsulfonamido, Independently selected from the group consisting of amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl and cyano ; Y ⁰ is of formula IV: [Formula IV] Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond, K ² is C, and D One or less of ⁵ , D ⁶ , J ^5, and J ⁶ is O, one or less of D ⁵ , D ⁶ , J ^5, and J ⁶ is S, and two of D ⁵ , D ⁶ , J ^5, and J ⁶ are O And when S, one of D ⁵ , D ⁶ , J ^5, and J ⁶ must be covalent, and up to four of D ⁵ , D ⁶ , J ^5, and J ⁶ are N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido, N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) and C (NR ²⁵ ) NR ²³ R ²⁴ It is selected from the group consisting of; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido and alkyl; Q ^s is CH ₂ ]. A compound according to claim 17, or a pharmaceutically acceptable salt thereof, characterized in that B is hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylprop Phenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl, 3- Methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1 -Heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptinyl, 3-heptinyl, 4-heptinyl, 5-heptinyl, 2-heptyl, 1-methyl -2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl-4-hexynyl , 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoro Ethyl, 2,2-difluoropropyl, 4-trifluorome -5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl and 3,3,3-trifluoropropyl Wherein each circle of group B is one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ at any up to 5 carbon atoms from the point of attachment of B to A Optionally substituted; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methyl Thio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amido Independently selected from the group consisting of docarbonyl, carboxy, cyano and Q ^b ; A is selected from the group consisting of a single covalent bond, NH, N (CH ₃ ), CH ₂ , CH ₃ CH and CH ₂ CH ₂ ; A is optionally selected from the group consisting of CH ₂ N (CH ₃ ), CH ₂ N (CH ₂ CH ₃ ), CH ₂ CH ₂ N (CH ₃ ) and CH ₂ CH ₂ N (CH ₂ CH ₃ ) With the proviso that B is hydrido; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, tri Fluoromethoxy, fluoro and chloro; R ² is selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl and 3-pyridyl Wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ and is two carbons apart from the carbon at the point of attachment and adjacent to R ⁹ Is optionally substituted by R ¹⁰ , two atoms away from the carbon at the point of attachment and carbon adjacent to R ¹³ is optionally substituted by R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted by R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N, N-dimethylamino, methylthio, trifluoromethyl, pentafluoro Roethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxy Independently selected from the group consisting of ethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy and cyano; R ¹⁰ and R ¹² represent hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxy Hydroxyethyl, 2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl Independently selected from the group consisting of, N-methylamino, dimethylamino, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo and cyano Become; Y ⁰ is selected from the group consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ pyridine, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene, ^{3-Q b -6-Q s} -2-R 16 -5-R 18 -4-R 19 ^{pyridine, 3-Q b -5-Q} s -4-R 16 -2-R 19 thiophene, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ furan, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ furan, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ pyrrole, 2-Q ^b -Q ^s -3-R ¹⁶ -4-R ¹⁷ pyrrole, 4-Q ^b- 2-Q ^s- 5-R ¹⁹ thiazole and 2-Q ^b- 5-Q ^s- 4-R ¹⁷ thiazole; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N- Methylamino, dimethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluorome Independently selected from the group consisting of oxy, fluoro, chloro, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, carboxy and cyano; Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ), provided that the Q ^b group is Is directly bonded to a carbon atom; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, methyl and ethyl; Q ^s is CH ₂ . The compound of claim 21, or a pharmaceutically acceptable salt thereof, characterized in that B is hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R) -2-butyl, (S) -2-butyl, tert-butyl, iso Butyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl, 3- Methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxy Hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl, 2- Dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S) -2-methylbutyl, 3-aminopropyl, 2-hexyl and 4-aminobutyl; A is selected from the group consisting of a single covalent bond, CH ₂ , CH ₃ CH and CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is selected from the group consisting of hydrido, hydroxy, amino, methyl, trifluoromethyl, fluoro and chloro; R ² is 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amimi Dinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl, 3-carboxy-5-hydroxy Phenyl, 3-carboxymethyl-5-aminophenyl, 3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl, 2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl , 3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2- Methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl , 3-trifluoroacetamidophenyl, 3-tri Fluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2 -Thienyl and 3-thienyl; Y ⁰ is selected from the group consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene and 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene; R ¹⁶ and R ¹⁹ are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; R ¹⁷ and R ¹⁸ are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy and cyano; Q ^b is selected from the group consisting of Q ^be wherein Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and methyl; Q ^s is CH ₂ . The compound of claim 22, or a pharmaceutically acceptable salt thereof, characterized in that B is hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R) -2-butyl, (S) -2-butyl, tert-butyl, iso Butyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl, 3- Methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxy Hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl, 2- Dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S) -2-methylbutyl, 3-aminopropyl, 2-hexyl and 4-aminobutyl; A is selected from the group consisting of a single covalent bond, CH ₂ , CH ₃ CH and CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is selected from the group consisting of hydrido, fluoro and chloro; R ² is 5-amino- ² -fluorophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, 3-carboxyphenyl, 3-cyanophenyl, 3-meth Oxycarbonylphenyl, phenyl and 3-pyridyl; Y ⁰ is selected from the group consisting of 5-amidino-2-thienylmethyl, 4-amidinobenzyl, 2-fluoro-4-amidinobenzyl and 3-fluoro-4-amidinobenzyl. The compound of claim 17, or a pharmaceutically acceptable salt thereof, selected from the group having the formula: [In the meal, R ² is 3-aminophenyl, B is 2,2,2-trifluoroethyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is (S) -2-butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 5-amino- ² -fluorophenyl, B is isopropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 2-methyl-3-aminophenyl, B is isopropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is ethyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is ethyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is CH; R ² is 3-aminophenyl, B is 2-propenyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is isopropyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is CH; R ² is 3-aminophenyl, B is isopropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 2-butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is (R) -2-butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 2-propynyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 3-pentyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is hydrido, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is ethyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 2-methylpropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 2-propyl, A is CH ₃ CH, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is propyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is CH; R ² is 3-aminophenyl, B is 6-amidocarbonylhexyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is tert-butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is tert-butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 3-hydroxypropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 2-methylpropyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is CH; R ² is 3-aminophenyl, B is butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 3-methoxy-2-propyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 3-methoxy-2-propyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 2-methoxy-2-ethyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 2-propyl, A is a single bond, Y ⁰ is 5-amidino-2-thienylmethyl and M is CH; R ² is 3-aminophenyl, B is 2-propyl, A is a single bond, Y ⁰ is 4-amidino-3-fluorobenzyl and M is CH; R ² is 3-carboxyphenyl, B is 2-propyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 2-propyl, A is a single bond, Y ⁰ is 4-amidino-3-fluorobenzyl and M is CH; R ² is 3-aminophenyl, B is 2,2,2-trifluoroethyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is (S) -2-butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 5-amino- ² -fluorophenyl, B is isopropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 2-methyl-3-aminophenyl, B is isopropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is ethyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is ethyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is N; R ² is 3-aminophenyl, B is 2-propenyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is isopropyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is N; R ² is 3-aminophenyl, B is isopropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 2-butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is (R) -2-butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 2-propynyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 3-pentyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is hydrido, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is ethyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 2-methylpropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 2-propyl, A is CH ₃ CH, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is propyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is N; R ² is 3-aminophenyl, B is 6-amidocarbonylhexyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is tert-butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is tert-butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 3-hydroxypropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 2-methylpropyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is N; R ² is 3-aminophenyl, B is butyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 3-methoxy-2-propyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 3-methoxy-2-propyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 2-methoxy-2-ethyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 2-propyl, A is a single bond, Y ⁰ is 5-amidino-2-thienylmethyl and M is N; R ² is 3-aminophenyl, B is 2-propyl, A is a single bond, Y ⁰ is 4-amidino-3-fluorobenzyl and M is N; R ² is 3-carboxyphenyl, B is 2-propyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 2-propyl, A is a single bond, Y ⁰ is 4-amidino-3-fluorobenzyl and M is CH. A compound according to claim 2 or a pharmaceutically acceptable salt thereof: [Wherein B is selected from the group consisting of C ₃ -C ₇ cycloalkyl and C ₄ -C ₆ saturated heterocyclyl, wherein each ring carbon is optionally substituted with R ³³ and the point of attachment of B to A Ring carbons except ring carbons are optionally substituted with oxo, provided that at least two ring carbons are not substituted at the same time with oxo, ring carbon or nitrogen adjacent to the carbon atom at the point of attachment is optionally substituted with R ⁹ or R ¹³ , and R Ring carbon or nitrogen adjacent to position ⁹ and two atoms away from the point of attachment is optionally substituted with R ¹⁰ , ring carbon or nitrogen adjacent to position R ¹³ and two atoms away from the point of attachment is optionally substituted with R ¹² and at the point of attachment dropping three-membered ring carbon or nitrogen adjacent to the R ¹⁰ position is optionally substituted with R ^11, dropping three atoms from the point of attachment ring carbon or nitrogen adjacent to the R ¹² position is optionally substituted by R ^33, Dropping four atoms in chakjeom ring carbon or nitrogen adjacent to the R ¹¹ and R ³³ position is optionally substituted by R ^34); R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, mono Alkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano; R ¹⁰ and R ¹² represent 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; R ³³ and R ³⁴ represent hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkyl ami Independently selected from the group consisting of dosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano and Q ^b ; A is selected from the group consisting of a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1 and pa is an integer selected from 0 to 3) And W ⁷ is selected from the group consisting of (R ⁷ ) NC (O) and N (R ⁷ ); R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl; R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds, O, S, NH and CH ₂ ; Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , and the point of attachment Two atoms away from carbon of and adjacent to R ⁹ are optionally substituted by R ¹⁰ , and two atoms away from carbon of the point of attachment and carbon adjacent to R ¹³ are optionally substituted by R ¹² and any adjacent to both R ¹⁰ and R ¹² Carbon is optionally substituted with R ¹¹ ; Y ⁰ is of formula IV: [Formula IV] Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond, K ² is C, and D One or less of ⁵ , D ⁶ , J ^5, and J ⁶ is O, one or less of D ⁵ , D ⁶ , J ^5, and J ⁶ is S, and two of D ⁵ , D ⁶ , J ^5, and J ⁶ are O And when S one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be covalent, and no more than four of D ⁵ , D ⁶ , J ⁵ and J ⁶ are N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl Is independently selected from the group consisting of alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that both R ²⁰ and R ²¹ are hydroxy No two R ²³ and R ²⁴ are hydroxy at the same time; R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, alkyl and hydroxy; Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ ]. The compound of claim 25, or a pharmaceutically acceptable salt thereof, characterized in that B is cyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaethan-3-yl, cyclopentyl, cyclohexyl, nord Boryl, 7-oxabicyclo [2.2.1] heptan-2-yl, bicyclo [3.1.0] hexane-6-yl, cycloheptyl, 2-morpholinyl, 3-morpholinyl, 4-mor Polyyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl , 3-pyrrolidinyl, 2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2-yl, 4H-pyran- 4-on-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl and 3-tetra-it is selected from the group consisting of tetrahydro-thienyl, wherein each ring carbon is optionally substituted with the R ^33, the ring carbon adjacent to the carbon of attachment points, and Cows R ⁹ or R ¹³ in any substituted, attached dropping two atoms from the point R ring carbon or nitrogen adjacent to the ^9-position is optionally substituted with R ^10, dropping the two atoms from the point of attachment ring carbon or nitrogen adjacent to the R ¹³ is Optionally substituted with R ¹² ; R ⁹ , R ¹¹ and R ¹³ are hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N -Methylamino, N, N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2 , 3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N- Methyl amidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl , N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and cyano are independently selected from the group consisting of; R ¹⁰ and R ¹² represent hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, meth Methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amido Dosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl Independently selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro, chloro, bromo and cyano Become; R ³³ represents hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacet Amido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2, 2,3,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl , N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbon Independently selected from the group consisting of carbonyl, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, cyano and Q ^b ; A is a single covalent bond, NH, N (CH ₃ ), N (OH), CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), N (CH ₃ ) C (O), C (O) NH , C (O) N (CH ₃ ), CH ₂ CH ₂ , CH ₂ CH ₂ CH ₂ , CH ₃ CHCH ₂ and CF ₃ CHCH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2 , 2-tetrafluoroethoxy, fluoro, chloro and bromo; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds, O, S, NH and CH ₂ ; Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4 -Pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyri Midinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl and 1,3,5-triazin-2-yl, wherein one carbon adjacent the carbon at the point of attachment Is substituted at R ⁹ lome, and the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , two atoms away from the carbon at the point of attachment, and the carbon adjacent to R ⁹ is optionally substituted with R ¹⁰ , from the carbon at the point of attachment. Two atoms apart and adjacent to R ¹³ are optionally substituted with R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ; Y ⁰ is selected from the group consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 2-Q ^b -4-Q ^s -3-R ¹⁶ -6-R ¹⁸ pyrazine, 3-Q ^b -6-Q ^s -2-R ¹⁸ -5-R ¹⁸ -4-R ¹⁹ pyridazine, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ pyrimidine, 5-Q ^b -2-Q ^s -3-R ¹⁶ -6-R ¹⁹ pyrimidine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ furan, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ furan, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ pyrrole, 2-Q ^b -Q ^s -3-R ¹⁶ -4-R ¹⁷ pyrrole, 4-Q ^b -2-Q ^s- 5-R ¹⁹ imidazole, 2-Q ^b -4-Q ^s- 5-R ¹⁷ imidazole, 3-Q ^b -5-Q ^s -4-R ¹⁶ isoxazole, 5-Q ^b -3-Q ^s -4-R ¹⁶ isoxazole, 2-Q ^b -5-Q ^s -4-R ¹⁶ pyrazole, 4-Q ^b -2-Q ^s- 5-R ¹⁹ thiazole and 2-Q ^b -5-Q ^s -4-R ¹⁷ thiazole; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, Amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsul Finyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy , 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydride Independently selected from the group consisting of hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is selected from the group consisting of Q ^be (where Q ^be is hydrido) and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that both R ²³ and R ²⁴ are not hydroxy simultaneously; R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, methyl, ethyl and hydroxy; Q ^s is selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ . The compound of claim 26, or a pharmaceutically acceptable salt thereof, characterized in that B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl, 2- (2R) -bicyclo [2.2.1] heptyl, 1-pyrrolidinyl, 1-piperidinyl , 1,1-dioxothiolan-3-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, 7-oxabizyl [2.2. 1] heptan-2-yl, bicyclo [3.1.0] hexane-6-yl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl , 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 4H -2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl , 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl and 3-tetrahydrothienyl; A is selected from the group consisting of a single covalent bond, CH ₂ , NHC (O), CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, tri Fluoromethoxy, fluoro and chloro; R ² is Z ⁰ -Q; Z ⁰ is selected from the group consisting of covalent single bonds, O, S, NH and CH ₂ ; Q is 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidino Phenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl, 3-carboxy-5-hydroxyphenyl , 3-carboxymethyl-5-aminophenyl, 3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl, 2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-meth Methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoroacet Amidophenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl and 3-thienyl is selected from the group consisting of; Y ⁰ is selected from the group of formula consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ Pyridine, 3-Q ^b -6-Q ^s -2-R ¹⁶ -5-R ¹⁸ -4-R ¹⁹ Pyridine, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene and 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene; R ¹⁶ and R ¹⁹ are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; R ¹⁷ and R ¹⁸ are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy and cyano; Q ^b is selected from the group consisting of Q ^be wherein Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and methyl; Q ^s is CH ₂ . The compound of claim 25, wherein the compound of formula [Wherein B is selected from the group consisting of C ₃ -C ₇ cycloalkyl and C ₄ -C ₆ saturated heterocyclyl, wherein each ring carbon is optionally substituted with R ³³ and the point of attachment of B to A Ring carbons except ring carbons are optionally substituted with oxo, provided that at least two ring carbons are not substituted at the same time with oxo, ring carbon and nitrogen adjacent to the carbon atom at the point of attachment are optionally substituted with R ⁹ or R ¹³ , and R Ring carbon or nitrogen adjacent to position ⁹ and two atoms away from the point of attachment is optionally substituted with R ¹⁰ , ring carbon or nitrogen adjacent to position R ¹³ and two atoms away from the point of attachment is optionally substituted with R ¹² and at the point of attachment dropping three-membered ring carbon or nitrogen adjacent to the R ¹⁰ position is optionally substituted with R ^11, dropping three atoms from the point of attachment ring carbon or nitrogen adjacent to the R ¹² position is optionally substituted with R ^33, section Search falling four atoms in that ring carbon or nitrogen adjacent to the R ¹¹ and R ³³ position is optionally substituted by R ^34); R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkyl amidosul Ponyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano; R ¹⁰ and R ¹² represent 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, carboxamido and cyano; R ³³ and R ³⁴ are hydrido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, Independently selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido and cyano; R ³³ is optionally Q ^b ; A is selected from the group consisting of a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1 and pa is an integer selected from 0 to 3) And W ⁷ is N (R ⁷ ); R ⁷ is selected from the group consisting of hydrido and alkyl; R ¹⁵ is selected from the group consisting of hydrido, halo, alkyl and haloalkyl; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of; R ² is Z ⁰ -Q; Z ⁰ is a covalent single bond; Q is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ , and the point of attachment Carbon two atoms away from carbon and adjacent to R ⁹ is optionally substituted with R ¹⁰ , and carbon two atoms away from carbon at the point of attachment and adjacent to R ¹³ is optionally substituted with R ¹² and any adjacent to both R ¹⁰ and R ¹² Carbon is optionally substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are hydrido, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkyl amidosul Ponyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido and cyano; R ¹⁰ and R ¹² represent 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, carboxamido and cyano; Y ⁰ is of formula IV: [Formula IV] Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently selected from the group consisting of C, N, O, S and a covalent bond, provided that at least one is a covalent bond, K ² is C, and D One or less of ⁵ , D ⁶ , J ^5, and J ⁶ is O, one or less of D ⁵ , D ⁶ , J ^5, and J ⁶ is S, and two of D ⁵ , D ⁶ , J ^5, and J ⁶ are O And when S one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be covalent, and no more than four of D ⁵ , D ⁶ , J ⁵ and J ⁶ are N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl , Alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkylamino and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is selected from the group consisting of NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and alkyl; Q ^s is CH ₂ ]. The compound of claim 28, or a pharmaceutically acceptable salt thereof, characterized in that B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl, 2- (2R) -bicyclo [2.2.1] heptyl, 1,1-dioxothiolan-3-yl , Oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, bicyclo [3.1.0] hexane-6-yl, 2-morpholinyl, 3- Morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrroli Diyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4- Tetrahydropyranyl, 2-tetrahydrothienyl and 3-tetrahydrothienyl, wherein each ring carbon is optionally substituted with R ³³ and the ring carbon and nitrogen adjacent to the carbon at the point of attachment are R Optionally substituted with ⁹ or R ¹³ , two atoms apart from the point of attachment Ring carbon or nitrogen, which is adjacent to the R ⁹ position, is optionally substituted by R ¹⁰ , two atoms away from the point of attachment and ring carbon or nitrogen adjacent to R ¹³ is optionally substituted by R ¹² ; R ⁹ , R ¹¹ and R ¹³ are hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N, N-dimethylamino, methylthio, trifluoromethyl, pentafluoro Roethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxy Independently selected from the group consisting of ethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy and cyano; R ¹⁰ and R ¹² represent hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxy Hydroxyethyl, 2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl Independently selected from the group consisting of, N-methylamino, dimethylamino, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo and cyano Become; R ³³ represents hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, carboxy, amino, N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethyl, Pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, cyano and Q ^b Independently selected from the group consisting of; A is selected from the group consisting of a single covalent bond, NH, N (CH ₃ ), CH ₂ , CH ₃ CH, CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, tri Fluoromethoxy, fluoro and chloro; R ² is selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl and 3-pyridyl Wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ and is two carbons apart from the carbon at the point of attachment and adjacent to R ⁹ Is optionally substituted with R ¹⁰ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ¹³ is optionally substituted with R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ; Y ⁰ is selected from the group consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 2-Q ^b -5-Q ^s -6-R ¹⁷ -4-R ¹⁸ -2-R ¹⁹ pyridine, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene, ^{3-Q b -6-Q s} -2-R 16 -5-R 18 -4-R 19 ^{pyridine, 3-Q b -5-Q} s -4-R 16 -2-R 19 thiophene, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ furan, 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ furan, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ pyrrole, 2-Q ^b -Q ^s -3-R ¹⁶ -4-R ¹⁷ pyrrole, 4-Q ^b- 2-Q ^s- 5-R ¹⁹ thiazole and 2-Q ^b- 5-Q ^s- 4-R ¹⁷ thiazole; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N- Methylamino, dimethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluorome Independently selected from the group consisting of oxy, fluoro, chloro, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, carboxy and cyano; Q ^b is selected from the group consisting of NR ²⁰ R ²¹ and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that the Q ^b group is bonded directly to a carbon atom; R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, methyl and ethyl; Q ^s is CH ₂ . The compound of claim 29, or a pharmaceutically acceptable salt thereof, characterized in that B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl, 2- (2R) -bicyclo [2.2.1] heptyl, 1,1-dioxothiolan-3-yl, oxetane -3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, 1-pyrrolidinyl and 1-piperidinyl; A is selected from the group consisting of a single covalent bond, CH ₂ , NHC (O), CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is selected from the group consisting of hydrido, hydroxy, amino, methyl, trifluoromethyl, fluoro and chloro; R ² is selected from the group consisting of 3-aminophenyl, 2,6-dichlorophenyl, 2-hydroxyphenyl, 5-amino-2-thienyl and 3-thienyl; Y ⁰ is selected from the group consisting of: 1-Q ^b -4-Q ^s -2-R ¹⁶ -3-R ¹⁷ -5-R ¹⁸ -6-R ¹⁹ benzene, 3-Q ^b -5-Q ^s -4-R ¹⁶ -2-R ¹⁹ thiophene and 2-Q ^b -5-Q ^s -3-R ¹⁶ -4-R ¹⁷ thiophene; R ¹⁶ and R ¹⁹ are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; R ¹⁷ and R ¹⁸ are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy and cyano; Q ^b is selected from the group consisting of Q ^be wherein Q ^be is hydrido and C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and methyl; Q ^s is CH ₂ . The compound of claim 30, or a pharmaceutically acceptable salt thereof, characterized in that B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl, 2- (2R) -bicyclo [2.2.1] heptyl, 1,1-dioxothiolan-3-yl, oxetane -3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl and 1-piperidinyl; A is selected from the group consisting of a single covalent bond, CH ₂ , CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is selected from the group consisting of hydrido, fluoro and chloro; R ² is selected from the group consisting of 3-aminophenyl, 2,6-dichlorophenyl, 2-hydroxyphenyl, phenyl, 5-amino-2-thienyl and 3-thienyl; Y ⁰ is selected from the group consisting of 5-amidino-2-thienylmethyl, 4-amidinobenzyl, 2-fluoro-4-amidinobenzyl and 3-fluoro-3-amidinobenzyl. The compound of claim 25, or a pharmaceutically acceptable salt thereof, selected from the group having the formula: [In the meal, R ² is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is CH; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is CH; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidino-3-fluorobenzyl and M is CH; R ² is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 5-amino- ² -thienyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is cyclopropyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 2- (2R) -bicyclo [2.2.1] heptyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is CH; R ² is 3-aminophenyl, B is cyclohexyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is oxalan-2-yl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is phenyl, B is 1-pyrrolidinyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 1-piperidinyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 1,1-dioxothiolan-3-yl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 2-hydroxyphenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is 1-pyrrolidinyl, A is CH ₂ CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CH; R ² is phenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-thienyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 2,6-dichlorophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH; R ² is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is CF; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is CF; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidino-3-fluorobenzyl and M is CF; R ² is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 5-amino- ² -thienyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is cyclopropyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is 2- (2R) -bicyclo [2.2.1] heptyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is CF; R ² is 3-aminophenyl, B is cyclohexyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is oxalan-2-yl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is phenyl, B is 1-pyrrolidinyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is 1-piperidinyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is 1,1-dioxothiolan-3-yl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 2-hydroxyphenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is 1-pyrrolidinyl, A is CH ₂ CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is CF; R ² is phenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-thienyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 2,6-dichlorophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CF; R ² is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is N; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is N; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidino-3-fluorobenzyl and M is N; R ² is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 5-amino- ² -thienyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is cyclopropyl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 2- (2R) -bicyclo [2.2.1] heptyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y ⁰ is 4-amidino-2-fluorobenzyl and M is N; R ² is 3-aminophenyl, B is cyclohexyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is oxalan-2-yl, A is CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is phenyl, B is 1-pyrrolidinyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 1-piperidinyl, A is CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 1,1-dioxothiolan-3-yl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 2-hydroxyphenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-aminophenyl, B is 1-pyrrolidinyl, A is CH ₂ CH ₂ CH ₂ , Y ⁰ is 4-amidinobenzyl and M is N; R ² is phenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 3-thienyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is N; R ² is 2,6-dichlorophenyl, B is cyclobutyl, A is a single bond, Y ⁰ is 4-amidinobenzyl and M is CH. Compounds of the formula: or pharmaceutically acceptable salts thereof [Wherein B is selected from the group consisting of aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³² and the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³⁶ and, dropping the two atoms from the carbon of the point of attachment is optionally substituted by R ³² carbon is R ³³ is adjacent to, falling two atoms from the carbon of attachment points, and optionally substituted with carbon, R ³⁵ adjacent to the R ^36, R ³³ and R ³⁵ both Any carbon adjacent to is optionally substituted with R ³⁴ ; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydride Roxy, amino, alkoxyamino, haloalkanoyl, nitro, lower alkylamino, alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, amidosulfonyl, monoalkyl Amidosulfonyl, dialkyl amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, alkylamino, carboalkoxy, carboxy, carboxamido, cyano and Q ^b Independently selected from the group consisting of; B is optionally hydrido, trialkylsilyl, C ₂ -C ₈ alkyl, C ₃ -C ₈ alkylenyl, C ₃ -C ₈ alkenyl, C ₃ -C ₈ alkynyl and C ₂ -C ₈ halo Selected from the group consisting of alkyl, wherein each member of the group B is selected from R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ at any of up to five carbon atoms from the point of attachment of B to A Optionally substituted with one or more of the group consisting of; B is optionally selected from the group consisting of C ₃ -C ₁₂ cycloalkyl and C ₄ -C ₉ saturated heterocyclyl, wherein each ring carbon is optionally substituted with R ³³ , ring carbon of the point of attachment of B to A Ring carbons except are optionally substituted with oxo, provided that at least two ring carbons are not substituted at the same time with oxo, ring carbon and nitrogen adjacent to the carbon at the point of attachment are optionally substituted with R ⁹ or R ¹³ , and from the point of attachment Ring carbon or nitrogen two atoms apart and adjacent to position R ⁹ is optionally substituted by R ¹⁰ , ring carbon or nitrogen two atoms apart and adjacent to R ¹³ optionally substituted by R ¹² and three atoms away from the point of attachment and R ¹⁰ The ring carbon or nitrogen adjacent to the position is optionally substituted by R ¹¹ , three atoms away from the point of attachment and the ring carbon or nitrogen adjacent to the R ¹² position is R ³³ ; Substituted, four rings from the point of attachment and adjacent to the R ¹¹ and R ³³ positions are optionally substituted with R ³⁴ ; R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy, halo Alkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio, arylsulfinyl, arylsulfamido, alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, Independently selected from the group consisting of haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido and cyano; A is selected from the group consisting of a single covalent bond and (CH (R ¹⁵ )) _pa- (W ⁷ ) _rr (wherein rr is an integer selected from 0 to 1 and pa is an integer selected from 0 to 3) And W ⁷ is selected from the group consisting of O, S, C (O), (R ⁷ ) NC (O), (R ⁷ ) NC (S) and N (R ⁷ ); R ⁷ is selected from the group consisting of hydrido, hydroxy and alkyl; R ¹⁵ is selected from the group consisting of hydrido, hydroxy, halo, alkyl and haloalkyl; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo Selected from the group consisting of; R ² is Z ⁰ -Q; Z ⁰ is a covalent single bond, (CR ⁴¹ R ⁴² ) _q (where q is an integer selected from 1 to 2), (CH (R ⁴¹ )) _g -W ^0- (CH (R ⁴² )) _p (formula Wherein g and p are integers independently selected from 0 to 3, and W ⁰ is selected from the group consisting of O, S and N (R ⁴¹ )) and (CH (R ⁴¹ )) _e -W ^22- (CH (R ⁴² )) _h (wherein e and h are integers independently selected from 0 to 1, and W ²² is CR ⁴¹ = CR ⁴² , 1,2-cyclopropyl, 1,2-cyclobutyl, 1, 2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 2,3-morpholinyl, 2,4-morpholinyl, 2, 6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 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-pyrroli Diyl, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydrofuranyl Is selected from the group consisting of Z ⁰ directly bonded to the pyrazinone ring; R ⁴¹ and R ⁴² are independently selected from the group consisting of hydrido, hydroxy and amino; Q is selected from the group consisting of hydrido (where Z ⁰ is not a covalent single bond), aryl and heteroaryl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , The other carbon adjacent to the carbon of is optionally substituted with R ¹³ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ⁹ is optionally substituted with R ¹⁰ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ¹³ is Optionally substituted with ^12, and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ; K is CHR ^4a , wherein R ^4a is selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl and haloalkyl; E ⁰ is selected from the group consisting of a covalent single bond, C (O) N (H), (H) NC (O), (R ⁷ ) NS (O) ₂ and S (O) ₂ N (R ⁷ ) ; Y ^AT is Q ^b -Q ^s ; Q ^s is (CR ³⁷ R ³⁸ ) _b (where b is an integer selected from 1 to 4, R ³⁷ is selected from the group consisting of hydrido, alkyl and haloalkyl, R ³⁸ is hydrido, Selected from the group consisting of alkyl, haloalkyl, aroyl and heteroaroyl, provided that there is at least one aroyl or heteroaroyl substituent and at least two aroyl or heteroaroyl are bonded to (CR ³⁷ R ³⁸ ) _b simultaneously And aroyl and heteroaroyl are optionally substituted with substituents selected from the group consisting of R ¹⁶ , R ¹⁷ , R ^18, and R ¹⁹ at 1 to 3 ring carbons, the aroyl and heteroaroyl directly to E ⁰ It is bonded to a carbon other than a carbon bonded to a combined CR ³⁷ R ^38, coupled to, two or more alkyl or haloalkyl not bonded simultaneously to the CR ³⁷ R ^38, the alkyl and haloalkyl aroyl or heterocyclic aroyl); R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl, Independently selected from the group consisting of alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; R ¹⁶ and R ¹⁹ are optionally Q ^b , provided that two R ¹⁶ and R ¹⁹ are not Q ^b at the same time and Q ^b is Q ^be ; Q ^b is NR ²⁰ R ²¹ , Q ^be where Q ^be is hydrido, N (R ²⁶ ) C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) and C (NR ²⁵ ) NR ²³ R ²⁴ Selected from the group consisting of: provided that two R ²⁰ and R ²¹ are not hydroxy, amino, alkylamino, or dialkylamino at the same time, and two R ²³ and R ²⁴ are simultaneously hydroxy, amino, alkylamino, or di Not alkylamino; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino. The compound of claim 33, wherein the compound of formula [Wherein B is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3- Pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl and 5-isoxazolyl, wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ³² , the other carbon adjacent to the carbon of attachment points is optionally substituted with R ^36, dropping the two atoms from the carbon of attachment point on the carbon adjacent to R ³² is optionally substituted with R ^33, dropping the two atoms from the point of attachment carbon-carbon adjacent to R ³⁶ Is optionally substituted with R ^35, and any carbon adjacent to both R ³³ and R ³⁵ is optionally substituted with R ³⁴ ; R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methyl Thio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amido Independently selected from the group consisting of docarbonyl, carboxy, cyano and Q ^b ; B is optionally hydrido, ethyl, 2-propynyl, 2-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl , Isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl -2-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl, 4 -Hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1- Ethyl-2-butenyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptinyl, 3-heptinyl, 4-heptinyl, 5-heptinyl , 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2 , 2,2-trifluoroethyl, 2,2-difluoro Phil, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl and 3,3,3-tree Selected from the group consisting of fluoropropyl, wherein each member of the group B is R ³² , R ³³ , R ³⁴ , R ³⁵ and R at any up to 5 carbon atoms from the point of attachment of B to A Optionally substituted with one or more of the group consisting of ³⁶ ; B is optionally cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl, 2- (2R) -bicyclo [2.2.1] heptyl, 1,1-dioxothiolane- 3-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, bicyclo [3.1.0] hexane-6-yl, 2-morpholinyl , 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1 -Pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl , 4-tetrahydropyranyl, 2-tetrahydrothienyl and 3-tetrahydrothienyl, wherein each ring carbon is optionally substituted with R ³³ , a ring carbon adjacent to the carbon at the point of attachment and nitrogen being optionally substituted with R ⁹ or R ^13, with attachment points Two emitter atom falling R ring carbon or nitrogen adjacent to the ^9-position is optionally substituted with R ^10, dropping the two atoms from the point of attachment ring carbon or nitrogen adjacent to the R ¹³ is optionally substituted with R ^12; R ⁹ , R ¹¹ and R ¹³ are hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N, N-dimethylamino, methylthio, trifluoromethyl, pentafluoro Roethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxy Independently selected from the group consisting of ethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy and cyano; R ¹⁰ and R ¹² represent hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxy Hydroxyethyl, 2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl Independently selected from the group consisting of, N-methylamino, dimethylamino, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo and cyano Become; A is selected from the group consisting of a single covalent bond, NH, N (CH ₃ ), CH ₂ , CH ₃ CH, CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2 , 2-tetrafluoroethoxy, fluoro, chloro and bromo; R ² is selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl and 3-pyridyl Wherein one carbon adjacent to the carbon at the point of attachment is optionally substituted with R ⁹ , the other carbon adjacent to the carbon at the point of attachment is optionally substituted with R ¹³ and is two carbons apart from the carbon at the point of attachment and adjacent to R ⁹ Is optionally substituted with R ¹⁰ , two atoms away from the carbon at the point of attachment and the carbon adjacent to R ¹³ is optionally substituted with R ¹² , and any carbon adjacent to both R ¹⁰ and R ¹² is optionally substituted with R ¹¹ ; Y ^AT is Q ^b -Q ^s ; Q ^s is selected from the group consisting of: C [R ³⁷ (benzoyl)] (CR ³⁷ R ³⁸ ) _b ], C [R ³⁷ (2-pyridylcarbonyl)] (CR ³⁷ R ³⁸ ) _b ], C [R ³⁷ (3-pyridylcarbonyl)] (CR ³⁷ R ³⁸ ) _b ], C [R ³⁷ (4-pyridylcarbonyl)] (CR ³⁷ R ³⁸ ) _b ], C [R ³⁷ (2-thienylcarbonyl)] (CR ³⁷ R ³⁸ ) _b ], C [R ³⁷ (3-thienylcarbonyl)] (CR ³⁷ R ³⁸ ) _b ], C [R ³⁷ (2-thiazolylcarbonyl)] (CR ³⁷ R ³⁸ ) _b ], C [R ³⁷ (4-thiazolylcarbonyl)] (CR ³⁷ R ³⁸ ) _b ] and C [R ³⁷ (5-thiazolylcarbonyl)] (CR ³⁷ R ³⁸ ) _b ] Wherein b is an integer selected from 1-3 and R ³⁷ and R ³⁸ are independently selected from the group consisting of hydrido, alkyl and haloalkyl, provided that aroyl and heteroaroyl are Optionally substituted at the ring carbon with a substituent selected from the group consisting of R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ , provided that R ¹⁷ and R ¹⁸ are other than meta and para carbons for the carbonyl of the benzoyl substituent and heteroaroyl substituent Optionally substituted at carbon selected from carbons of said benzoyl and heteroaroyl are bonded to a carbon directly bonded to the amide nitrogen of the 1- (amidocarbonylmethylene) group, and at least two alkyl or haloalkyl are simultaneously CR ³⁷ R ³⁸ Not bound to); R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N- Methylamino, dimethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluorome Independently selected from the group consisting of oxy, fluoro, chloro, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, carboxy and cyano; Q ^b is selected from the group consisting of NR ²⁰ R ²¹ and C (NR ²⁵ ) NR ²³ R ²⁴ , provided that the Q ^b group is bonded directly to a carbon atom; R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido, methyl and ethyl. The compound of claim 34, or a pharmaceutically acceptable salt thereof, characterized in that B is 2-aminophenyl, 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-chlorophenyl, 4-chlorophenyl, 3 , 4-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 3,4-difluorophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3-methoxyaminophenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoromethylphenyl, 2-imidazolyl, 2-pyridyl, 3-pyridyl, 5-chloro-3-trifluoro Methyl-2-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl and 3-trifluoromethyl-2-pyridyl; B is optionally hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R) -2-butyl, (S) -2-butyl, tert- Butyl, isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl , 3-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl , 2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S) -2-methylbutyl, 3-aminopropyl, 2-hexyl and 4-aminobutyl; B is optionally cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl, 2- (2R) -bicyclo [2.2.1] heptyl, 1,1-dioxothiolan-3-yl , Oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, 1-pyrrolidinyl and 1-piperidinyl; A is selected from the group consisting of a single covalent bond, CH ₂ , CH ₃ CH, CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, tri Fluoromethoxy, fluoro and chloro; R ² is 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amimi Dinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl, 3-carboxy-5-hydroxy Phenyl, 3-carboxymethyl-5-aminophenyl, 3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl, 2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl , 3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2- Methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl , 3-trifluoroacetamidophenyl, 3-tri Fluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2 -Thienyl and 3-thienyl; Y ^AT is Q ^b -Q ^s ; Q ^s is selected from the group consisting of: [CH (benzoyl)] (CH ₂ ) _b , [CH (2-pyridylcarbonyl)] (CH ₂ ) _b , [CH (3-pyridylcarbonyl)] (CH ₂ ) _b , [CH (4-pyridylcarbonyl)] (CH ₂ ) _b , [CH (2-thienylcarbonyl)] (CH ₂ ) _b , [CH (3-thienylcarbonyl)] (CH ₂ ) _b , [CH (2-thiazolylcarbonyl)] (CH ₂ ) _b , [CH (4-thiazolylcarbonyl)] (CH ₂ ) _b and [CH (5-thiazolylcarbonyl)] (CH ₂ ) _b Wherein b is an integer selected from 1 to 3, wherein the aroyl and heteroaroyl are optionally substituted with substituents selected from the group consisting of R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ in a ring carbon of 1 to 3 Provided that R ¹⁷ and R ¹⁸ are optionally substituted on a carbon selected from carbon other than meta and para carbon for carbonyl of the benzoyl substituent and heteroaroyl substituent, wherein the benzoyl and heteroaroyl substituent is 1- (amido Bound to carbon directly bonded to the amide nitrogen of the carbonylmethylene) group); R ¹⁶ and R ¹⁹ are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro and cyano; R ¹⁷ and R ¹⁸ are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy and cyano; Q ^b is C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydrido and methyl. The compound of claim 35, or a pharmaceutically acceptable salt thereof, characterized in that B is 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 4-methylphenyl, phenyl, 2- Imidazolyl, 3-pyridyl, 4-pyridyl and 3-trifluoromethyl-2-pyridyl; B is optionally hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R) -2-butyl, (S) -2-butyl, tert- Butyl, isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl , 3-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl , 2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S) -2-methylbutyl, 3-aminopropyl, 2-hexyl and 4-aminobutyl; B is optionally cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl, 2- (2R) -bicyclo [2.2.1] heptyl, 1,1-dioxothiolan-3-yl , Oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl and 1-piperidinyl; A is selected from the group consisting of a single covalent bond, CH ₂ , CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is selected from the group consisting of N and R ¹ -C; R ¹ is selected from the group consisting of hydrido, hydroxy, amino, methyl, trifluoromethyl, fluoro and chloro; R ² is 3-aminophenyl, benzyl, 2,6-dichlorophenyl, 5-amino-2-thienyl, 5-amino-2-fluorophenyl, 3-amino-2-methylphenyl, 5-amino-2- Methylthiophenyl, 3-carboxyphenyl, 3-cyanophenyl, 3-chlorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 3-methoxycarbonylphenyl, 3- Dimethylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, phenyl, 3-pyridyl, 3-trifluoroacetamidophenyl, 3-bromo-2-thienyl, 2-thienyl and 3-thienyl is selected from the group consisting of; Y ^AT is 5-guanidino-1-oxo- (2-thiazolyl) -2-pentyl, 5-guanidino-1-oxo-1- (4-thiazolyl) -2-pentyl, 5-sphere Anidino-1-oxo-1- (5-thiazolyl) -2-pentyl, 5-guanidino-1-oxo-1- (4-amino-2-thiazolyl) -2-pentyl and 5-sphere Selected from the group consisting of anidino-1-oxo-1-phenyl-2-pentyl. The compound of claim 33, or a pharmaceutically acceptable salt thereof, selected from the group having the formula: [In the meal, R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CH Or; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CH ; R ² is benzyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CH ; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CH ; R ² is benzyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CH ; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CH ; R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CF Or; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CF ; R ² is benzyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CF ; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CF ; R ² is benzyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CF ; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CF ; R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CCl Or; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CCl ; R ² is benzyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CCl or ; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CCl ; R ² is benzyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CCl or ; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CCl ; R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is N Or; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is N ; R ² is benzyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is N ; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is N ; R ² is benzyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is N ; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is N ]. 38. A composition for inhibiting a thrombotic state in blood containing a compound according to any one of claims 8, 16, 24, 32 and 37 and a pharmaceutically acceptable carrier. 37. A compound according to any one of claims 1 to 7, 9 to 15, 17 to 23, 25 to 31, and 33 to 36 and a pharmaceutical A composition for inhibiting a thrombotic state in blood containing an acceptable carrier. 40. A method of inhibiting a thrombotic state in blood, comprising adding a therapeutically effective amount of the composition according to claim 38 or 39 to the blood. A method of inhibiting the formation of platelet aggregation in the blood, comprising adding a therapeutically effective amount of the composition according to claim 38 or 39 to the blood. A method of inhibiting blood clot formation in a blood comprising adding a therapeutically effective amount of the composition according to claim 38 or 39 to the blood. A method of treating or preventing venous thromboembolism and pulmonary embolism in a mammal comprising administering to the mammal a therapeutically effective amount of the composition according to claim 38 or 39. A method of treating or preventing deep vein thrombosis in a mammal comprising administering to the mammal a therapeutically effective amount of the composition according to claim 38 or 39. 40. A method of treating or preventing psychogenic thromboembolism in a mammal, comprising administering to the mammal a therapeutically effective amount of the composition according to claim 38 or 39. A method of treating or preventing thromboembolic stroke in humans and other mammals comprising administering to the mammal a therapeutically effective amount of the composition according to claim 38 or 39. A method of treating or preventing thrombosis associated with cancer and cancer chemotherapy in humans and other mammals, comprising administering to the mammal a therapeutically effective amount of the composition according to claim 38 or 39. A method of treating or preventing unstable angina in humans and other mammals, comprising administering to the mammal a therapeutically effective amount of the composition according to claim 38 or 39. A method of inhibiting blood clot formation in a blood comprising adding a therapeutically effective amount of a compound according to any one of claims 1 to 37 to a blood with a therapeutically effective amount of a fibrinogen receptor antagonist. Use of a compound according to claims 1 to 37 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for inhibiting thrombus formation, treating thrombus formation, or preventing thrombus formation in a mammal.