JP2002544262A - Substituted polycyclic aryl and heteroaryl pyrimidinones as useful anticoagulants - Google Patents

Abstract

(57) Abstract: The present invention relates to a substituted polycyclic aryl and heteroaryl pyridone compound represented by the formula (I) or a pharmaceutically acceptable salt represented by the formula (I) wherein Ψ is selected from the group consisting of NH and NOH: Accordingly, compounds useful as inhibitors of serine proteases of the coagulation cascade, and compounds, compositions and methods for use in anticoagulant therapy for the treatment and prevention of various thrombotic conditions, including coronary and cerebrovascular disease About. Embedded image (I)

Description

DETAILED DESCRIPTION OF THE INVENTION

FIELD OF THE INVENTION The present invention relates to compounds, compositions and methods in the field of anticoagulant therapy, in particular for the prevention and treatment of thrombotic symptoms such as coronary and cerebrovascular diseases. More particularly, the present invention relates to substituted polycyclic aryl and heteroaryl pyrimidinone compounds that inhibit serine proteases in the clotting cascade.

BACKGROUND OF THE INVENTION Physiological systems control the fluidity of mammalian blood [Majerus, PW et al: Antico
agulant, Thrombolytic, and Antiplplatelet Drugs.Hardman, JG and Limb
ird, LE, editors: Goodman &Gilman's The Pharmacological Basis of Ther
apeutics. 9th edition.New York, McGraw-Hill Book Co., 1996, pp. 1341-13
43]. Blood remains fluid in the vasculature, but must stop blood loss from damaged blood vessels as soon as it stops bleeding. Hemostasis or clotting begins when platelets first adhere to macromolecules in the subendothelial region of damaged and / or damaged blood vessels. These platelets aggregate to form a primary hemostatic plug, which stimulates local activation of clotting factors in plasma, leading to the formation of fibrin clots that enhance platelet aggregation.

[0003] Plasma clotting factors include factors II, V, VII, VIII, IX, X, XI and X
II; these are also called protease zymogens. These clotting factors or protease zymogens are known as the so-called "coagulatio
n cascade) ”or activated by a serine protease that causes clotting in a chain reaction [Handein, RI: Bleeding and Thrombosis. Wilson, J., et al. edit
ors: Harrison's Principles of Internal Medicine.12th Edition, New York,
McGraw-Hill Book Co., 1991, p.350]. Clotting or clotting occurs in two different ways. The endogenous or tactile pathway converts XII to XIIa, XIa, IXa
To lead to the conversion of X to Xa. Xa, together with Factor Va, converts prothrombin (II) to thrombin (IIa), leading to the conversion of fibrinogen to fibrin. Fibrin polymerization leads to fibrin clots. The extrinsic pathway is initiated by the conversion of clotting factor VII to VIIa by Xa. The presence of tissue factor and VIIa promotes the formation of Xa in the presence of calcium ions and phospholipids. Formation of Xa results in thrombin, fibrin and the above fibrin clots. The presence of or many of these different coagulation factors and two separate pathways of clotting allows effective and selective control and a better understanding of some of the processes of coagulation or clotting.

[0004] Although clotting as a result of vascular damage is a critical physiological process for mammals such as humans, clotting can also lead to pathology. If platelet coagulation and / or fibrin clots block (eg, occlude) blood vessels, this pathological process is called thrombosis. Arterial thrombosis can lead to ischemic necrosis of tissue supplied by arteries. If thrombosis occurs in the coronary arteries, it can result in a myocardial infarction or heart attack. Thrombosis that occurs in a vein can cause cells drained by the vein to cause edema and inflammation. Deep vein thrombosis may be exacerbated by pulmonary obstruction. Prevention or treatment of clot formation in blood vessels is based on the inhibition of platelet aggregate formation, fibrin formation, thrombus formation, and emboli formation, resulting in unstable angina, refractory angina, myocardium Infarction, transient ischemic attack,
It is therapeutically useful for atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular blood coagulation, increased ocular fibrin, and reocclusion or restenosis of open vessels.

[0005] There have been several reports of non-peptide and peptide pyrimidinone compounds that act as inhibitors of the coagulation factors present in the coagulation cascade or clot process. Van Boeckel et al., PCT Patent Application WO 98/47876, describe peptide 6-alkylpyridones and 2-alkylpyrimidinones as anti-occlusion compounds. Zhu and Scarborough PCT Patent Application WO 98/1654
7, 3- (N-heterocyclylamino) 4,5,6-substituted-pyridonylacetamides and 2,4 containing an amide substituent and having activity against mammalian factor Xa
-Substituted-5- (N-heterocyclicamino) -pyrimidinonyl-acetamides have been described. U.S. Pat. No. 5,656,645 to Tamura et al. Discloses an amide substituent-containing 4,5,6-substituted-3-aminopyridonyl-acetamide, 1,6-substituted-5 having a formyl function and having an activity on thrombin. -Aminouracynylacetamide and 2,4-substituted-5-aminopyrimidinonyl-acetamide have been described. In U.S. Pat. No. 5,658,930, Tamura et al. Once again have a formyl function and an activity on thrombin containing an amide substituent-containing 4,4.
5,6-Substituted-3-aminopyridonyl-acetamides, 1,6-substituted-5-aminouracinylacetamides and 2,4-substituted-5-aminopyrimidinonyl-acetamides have been described. Further, Tamura et al., PCT Patent Application 96/186.
44, 97/46207, amide substituent containing 4,5,6-substituted-3-aminopyridonyl-acetamide, 1,6-substituted-5, which has a formyl function, contains a substituent, and has an activity on thrombin. -Aminouracinyl-acetamide and 2,4-substituted-5-amino-pyrimidinonylacetamide have been described. Suzuki et al., PCT Patent Application WO 98/09949, discloses 2-
Heterocyclyl acetamide derivatives have been described, which report on inhibiting proteases, in particular, timase inhibitors.

SUMMARY OF THE INVENTION [0006] Aspects of the present invention are useful for anticoagulant treatment and have a general structure

Embedded image A compound represented by the formula (I) is provided.

[0007] In another aspect of the present invention, there is provided the prevention and treatment of thrombotic symptoms such as coronary artery disease, cerebrovascular disease and other coagulation related diseases. Such thrombotic symptoms are prevented and treated by administering an effective amount of a compound of formula (I) to a patient in need thereof. Various other aspects and advantages of the invention will become apparent in the following description of the invention.

Description of the Invention The present invention provides a compound of formula (I):

Embedded image Formula (I)

Wherein J is a group selected from the group consisting of O and S; J is CH-R⁶And NR⁶A group selected from the group consisting of
Where R⁶Is an R which forms a heteroaryl ring with 5 to 8 members^4a, R ^4b , R³⁹, R⁴⁰, R⁵, R¹⁴And R^FifteenSelected from the group consisting of
A linear spacer moiety having a chain length of 1-4 atoms attached to the binding site of the substituent; J is optionally CH-R⁶And NR⁶A group selected from the group consisting of
Where R⁶Is an R which forms a heteroaryl ring with 5 to 8 members^4aand
R^4bA linear spacer moiety having a chain length of 1-4 atoms attached to both binding sites; J is optionally CH-R⁶And NR⁶A group selected from the group consisting of
Where R⁶Is an R which forms a heteroaryl ring with 5 to 8 members³⁹and
R⁴⁰A linear spacer moiety having a chain length of 1 to 4 atoms attached to both binding sites; B has the formula (V):

[0010]

Embedded image (V)

(Wherein, D¹, D², J¹, J²And K¹Independently represent C, N, O, S and
And a group selected from the group consisting of:
There is no, D¹, D², J¹, J²And K¹More than one is O
Never, D¹, D², J¹, J²And K¹S is more than one of
Never, D¹, D², J¹, J²And K¹Is O and S, then D ¹ , D², J¹, J²And K¹One must be a covalent bond, and
D¹, D², J¹, J²And K¹More than four cannot be N
But R³², R³³, R³⁴, R³⁵And R³⁶Are each independently a carbon
Maintain tetravalent properties, nitrogen trivalent properties, sulfur divalent properties, and oxygen divalent properties.
Selected to have a group represented by:

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 hydride, acetamido, haloacetamide, amidino, guanidino, dialkylsulfonium,
Trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, 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, alkoxyalkyl, haloalkoxyalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedi Oxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, Arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinyl , Arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamide, alkylaminosulfonyl, amidosulfonyl, monoalkylamidosulfonyl , Dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamide, diarylamidosulfonyl, monoalkylmonoarylamidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alka Yl, alkenoyl, aroyl, heteroaroyl, aralcanoyl, heteroaralkanoyl, 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, carboalkoxy, alkoxycarboxamide, alkylamidecarbonylamide, arylamide From carbonylamide, carbalkoxyalkyl, carbalkoxyalkenyl, carboxy, carbalkalalkoxy, carboxyamide, carboxyamidoalkyl, cyano, carbhaloalkoxy, phosphono, phosphonoalkyl, dialalkoxyphosphono and dialalkoxyphosphonoalkyl A group selected from the group consisting of:

[0013] R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵And R³⁶Is optional
And independently Q^bWhere R¹⁶And R¹⁹More than one at the same time Q ^b Is not, Q^bIs Q^beR³²And R³³, R³³And R³⁴, R³⁴And R³⁵, And R^{3 5} And R³⁶Are optionally selected to form a spacer pair independently.
The selected group, wherein the spacer pair is a cycloalkane having 5 to 8 members
Nyl ring, partially saturated heterocyclyl ring having 5 to 8 members, 5 to 6
Of a ring selected from the group consisting of heteroaryl rings and aryls having adjacent members of
Having three to six adjacent atoms that bind to the binding site of the spacer pair for formation.
Used together to form one linear part, provided that the spacer pair R³²And
And R³³, R³³And R³⁴, R³⁴And R³⁵, And R³⁵And R^{3 6} No more than one is used simultaneously; R⁹And R¹⁰, R¹⁰And R¹¹, R¹¹And R¹², And R¹² And R¹³Are, optionally, independently selected for spacer pair formation.
Wherein the spacer pair is a cycloalkenyl ring having from 5 to 8 neighbors
, A partially saturated heterocyclyl ring with 5 to 8 members, 5 to 6 members
Membered heteroaryl ring and the formation of a ring selected from the group consisting of aryl
Have three to six adjacent atoms that bind to the binding site of the spacer pair.
Used together to form a chain, provided that the spacer pair R⁹And R¹⁰ , R¹⁰And R¹¹, R¹¹And R¹², And R¹²And R¹³One of
More are not used simultaneously; B is a compound of formula (VI):

[0014]

Embedded image (VI)

(Where D³, D⁴, J³And J⁴Independently represent C, N, O, S and shared
A group selected from a bond, but D³, D⁴, J³And J⁴More than one of
Never O, D³, D⁴, J³And J⁴S is more than one of
Never, D³, D⁴, J³And J⁴Is O and S, then D³, D ⁴ , J³And J⁴One must be a covalent bond, and D³, D⁴, J ³ And J⁴Is not N, provided that R³², R³³ , R³⁴And R³⁵Are independently the tetravalent properties of carbon and the trivalent properties of nitrogen
, Groups selected to maintain the divalent nature of sulfur and the divalent nature of oxygen)
B is hydride, trialkylsilyl, C2-C8 alkyl, C
3-C8 alkenyl, C3-C8 alkylenyl, C3-C8 alkynyl, C2-
A group selected from the group consisting of C8 haloalkyl and C3-C8 haloalkenyl
Wherein each member of B is optionally up to 6 atoms from the site of attachment of B to A
Any of the carbon atoms including³², R³³, R³⁴, R³⁵And R³⁶Or
B is optionally substituted with C3-C15 cycloalkyl, C5-C10 cycloalkene.
Nyl, C4-C12 saturated heterocyclyl and C4-C9 partially saturated heterocyclyl
A ring selected from the group consisting of³³Put in
All ring carbons other than the ring carbon of the bonding site of B to A may be
If desired, oxo may be substituted, provided that more than one ring carbon is not substituted with oxo at the same time and the ring adjacent to the carbon atom at the point of attachment is not substituted.
Carbon and nitrogen may optionally be R⁹And R¹³May be substituted with ⁹ A ring carbon or nitrogen atom adjacent to the site and two atoms away from the binding site may optionally be
R¹⁰May be substituted with¹³Position, 2 atoms away from the binding site
The ring carbon or nitrogen atom is optionally R¹²May be replaced by
R 3 atoms away from the merging site¹⁰Ring carbon or nitrogen atom adjacent to the position
Than R¹¹May be substituted with 3 atoms away from the binding site,¹²Next to
The ring carbon or nitrogen atom in contact may optionally be³³May be replaced by
R atoms 4 atoms away from the binding site¹¹And R³³Ring carbon or nitrogen source adjacent to
The child is optionally R³⁴May be substituted;

A is a single covalent bond, (W⁷)_rr-(CH (R^Fifteen))_paAnd (CH (R ^Fifteen ))_pa− (W⁷)_rrA group selected from the group consisting of: wherein rr is 0
An integer selected from 0 to 1, pa is an integer selected from 0 to 6, and W⁷Is
O, S, C (O), C (S), C (O) S, C (S) O, C (O) N (R⁷),
C (S) N (R⁷), (R⁷) NC (O), (R⁷) NC (S), S (O), S
(O)₂, S (O)₂N (R⁷), (R⁷) NS (O)₂, Se (O), Se (
O)₂, Se (O)₂N (R⁷), (R⁷) NSe (O)₂, P (O) (R⁸)
, N (R⁷) P (O) (R⁸), P (O) (R⁸) N (R⁷), C (NR⁷) N
(R⁷), (R⁷) NC (NR⁷), (R⁷) NC (NR⁷) NR⁷And N (
R⁷A group selected from the group consisting of rr and pa
No more can be zero at the same time; R⁷And R⁸Is independently hydride, hydroxy, alkyl, alkenyl
, Aryl, aralkyl, aryloxy, alkoxy, alkenyloxy, a
Alkylthio, alkylamino, arylthio, arylamino, acyl, alloy
, Heteroaroyl, aralkoxyalkyl, heteroaralkoxyalkyl,
Reeloxyalkyl, alkoxyalkyl, alkenyloxyalkyl, al
Kirthioalkyl, alkoxyalkyl, heteroaralkoxyalkyl, alk
Rusulfinylalkyl, alkylsulfonylalkyl, heteroaryl, hete
Lowaryloxy, heteroarylamino, heteroaralkyl, heteroaralkyl
Consisting of oxy, heteroaralkylamino and heteroaryloxyalkyl
A group selected from the group consisting of

R ¹⁴ , R ¹⁵ , R ³⁷ , R ³⁸ , R ³⁹ , R ⁴⁰ , R ⁴¹ and R ⁴² are
Independently, amidino, hydroxyamino, hydride, hydroxy, halo, cyano, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, aminoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamino, alkoxy , Alkylthio,
Arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyl Oxyalkyl, alkylthioalkyl, arylthioalkyl,
Cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxy Alkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl,
Partially saturated heterocyclyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carbalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkyl Sulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsulfonylalkyl, heteroarylsulfonylalkyl, heteroaryl Sulph Alkylsulfonyl, heteroarylsulfonyl, heteroaryl sulfinyl alkyl, aralkyl sulfinyl alkyl, aralkyl sulphonyl alkyl, carboxy, carboxyalkyl, carboalkoxy, Karubokishiado,
Carboxamide alkyl, carboxy aralkoxycarbonyl, trialkylsilyl, dialkoxyphosphono, Giara Turkey alkoxy phosphono, dialkoxyphosphono alkyl and Giara Turkey alkoxy phosphono group selected from the group consisting of alkyl, provided that, R ^{3 7} And R ³⁸ are independently groups selected from groups other than formyl and 2-oxoacyl;

When R ¹⁴ and R ¹⁴ are attached to different carbons, optionally a covalent bond,
Alkylene, haloalkylene and cycloalkyl rings having 5 to 8 members,
To form a group consisting of a linear spacer moiety selected to form a ring selected from the group consisting of a cycloalkenyl ring having 5 to 8 members and a heterocyclyl ring having 5 to 8 members. R ¹⁴ and R ¹⁵ are optionally covalent, when attached to different carbons,
Alkylene, haloalkylene and cycloalkyl rings having 5 to 8 members,
To form a group consisting of a linear spacer moiety selected to form a ring selected from the group consisting of a cycloalkenyl ring having 5 to 8 members and a heterocyclyl ring having 5 to 8 members. R ¹⁵ and R ¹⁵ are optionally covalent, when attached to different carbons,
Alkylene, haloalkylene and cycloalkyl rings having 5 to 8 members,
To form a group consisting of a linear spacer moiety selected to form a ring selected from the group consisting of a cycloalkenyl ring having 5 to 8 members and a heterocyclyl ring having 5 to 8 members. Are used together; Ψ is NR ⁵ , O, C (O), C (S), S, S (O), S (O) ₂ , ON (
R ⁵ ), a group selected from the group consisting of P (O) (R ⁸ ) and CR ³⁹ R ⁴⁰ ;
R ⁵ is hydride, hydroxy, amino, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxy, aralkoxy, alkoxy, alkenyloxy, alkylthio, arylthio, aralkoxyalkyl, heteroaralkoxyalkyl, aryloxyalkyl, alkoxy Alkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, Haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloa Lucenyloxyalkyl, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, heteroaryl, heteroarylalkyl, monocarboalkoxyalkyl, monocarboalkoxy, dicarboalkoxyalkyl, monocarboxyamide, monocyanoalkyl, dicyanoalkyl, carboalkoxy A group selected from the group consisting of cyanoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl and dialkoxyphosphonoalkyl;

When R ³⁹ and R ⁴⁰ are bonded to the same carbon, optionally oxo, thiono, R ⁵ —N, alkylene, haloalkylene and a cycloalkyl ring having 3 to 8 members, and 3 to 8 A group consisting of a linear spacer moiety having 2 to 7 adjacent atoms selected to form a ring selected from the group consisting of a cycloalkenyl ring having adjacent members and a heterocyclyl ring having 3 to 8 adjacent members. M is a group selected from the group consisting of N and R ¹ -C; and R ² and R ¹ are independently Z ⁰ -Q, hydride, alkyl, alkenyl and halo. A group selected from the group consisting of: R ¹ is optionally amino, aminoalkyl, alkylamino, amidino,
Guanidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, alkylthio, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, nitro, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, A group selected from the group consisting of aralcanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, and phosphono; R ² is optionally amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, heteroaryl Amino, amino, nitro, alkylamino, arylamino, aralkylamino, alka Yl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, hetero alkanoyl, hydroxyalkyl haloalkyl, groups selected from the group consisting of cyano and phosphono; ^{R 2} and ^R 4a, ^{R 2} and ^R 4b, ^{R 2} and ^{R 14} And R ² and R ¹⁵ are, optionally, independently, the spacer pair is a cycloalkenyl ring having from 5 to 8 members, a partially saturated heterocyclyl ring having from 5 to 8 members. Are used together to form a linear portion having from 2 to 5 adjacent atoms attached to the binding site of the spacer pair, provided that the spacer pairs R ² and R ^4a , R ² and R ^4b , R ² And more than one of R ¹⁴ , and R ² and R ¹⁵ are not used simultaneously; R ² is optionally, and independently, are selected from linear section with two to five adjacent atoms bonded to the binding site of both R ^4a and R ^4b form a heterocyclyl ring having 5-8 one proximity membered Group;

Z⁰Is a single covalent bond, (CR⁴¹R⁴²)_q, Where q is selected from 1-6
Integer, (CH (R⁴¹)_g-W⁰-(CH (R⁴²))_p, Here, g
And p are independently integers selected from 0 to 3, W⁰Are O, S, C (O),
C (S), C (O) O, C (S) O, C (O) S, C (S) S, C (O) N (R ⁴¹ ), (R⁴¹) NC (S), C (S) N (R⁴¹), (R⁴¹) NC (S)
, OC (O) N (R⁴¹), (R⁴¹) NC (O) O, SC (S) N (R⁴¹)
, (R⁴¹) NC (S) S, SC (O) N (R⁴¹), (R⁴¹) NC (O) S
, OC (S) N (R⁴¹), (R⁴¹) NC (S) O, N (R⁴²) C (O) N
(R⁴¹), (R⁴¹) NC (O) N (R⁴²), N (R⁴²) C (S) N (R ⁴¹ ), (R⁴¹) NC (S) N (R⁴²), S (O), S (O)₂, S (O) ₂ N (R⁴¹), N (R⁴¹) S (O)₂, Se, Se (O), Se (O)₂,
Se (O)₂N (R⁴¹), N (R⁴¹) Se (O)₂, P (O) (R⁸), N
(R⁷) P (O) (R⁸), P (O) (R⁸) N (R⁷), N (R⁴¹), ON
(R⁴¹) And SiR²⁸R²⁹And a group selected from the group consisting of
(R⁴¹)_e-W²²-(CH (R⁴²))_hA group selected from
And h are each independently an integer selected from 0 to 2, W²²Is CR⁴¹= CR^{4 2} , R⁴¹R⁴²= C; vinylidene), ethinylidene (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-piper
Dinyl, 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-pi
Loridinyl, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-
Tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydro
A group selected from the group consisting of drofuranyl, provided that R⁴¹And R⁴²Is N
And a group selected from groups other than halo and cyano, and Z⁰ Is directly attached to the pyrimidinone ring;

R ²⁸ and R ²⁹ are independently hydride, hydroxyalkyl, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl,
Acyl, aroyl, aralcanoyl, heteroaroyl, aralkoxyalkyl,
Alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, Cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, per Haloaryloxyalkyl, heteroaryl, heteroarylalkyl, Teloarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl, dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyl, carboalkoxyalkyl, dicarboalkoxyalkyl, cyanocycloalkyl, dicyanocycloalkyl, carboxamidocyclo Alkyl, dicarboxamidocycloalkyl, carboalkoxycyanocycloalkyl, carboalkoxycycloalkyl,
Dicarboalkoxycycloalkyl, formylalkyl, acylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, aralkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl , carboxy, dialkoxyphosphono, groups selected from the group consisting of dialkoxyphosphono alkyl and Giara Turkey carboxymethyl phosphonoalkyl; R ²⁸ and R ²⁹ optionally has 2-7 single neighbor atoms, 3 A cycloalkyl ring having 8 members, a cycloalkenyl ring having 3 to 8 members and a heterocyclyl ring having 3 to 8 members. To form a linear spacer portion that forms a ring selected from the group consisting of, utilized both; Q is formula (II):

[0022]

Embedded image (II)

(Where D is¹, D², J¹, J²And K¹Independently represent C, N, O, S and
And a group selected from the group consisting of:
There is no, D¹, D², J¹, J²And K¹More than one is O
Never, D¹, D², J¹, J²And K¹S is more than one of
Never, D¹, D², J¹, J²And K¹Is O and S, then D ¹ , D², J¹, J²And K¹One must be a covalent bond, and
D¹, D², J¹, J²And K¹More than four cannot be N
But R⁹, R¹⁰, R¹¹, R¹²And R¹³Is each independently 4 carbon atoms
Maintains trivalent nature of nitrogen, trivalent nature of sulfur, divalent nature of sulfur and divalent nature of oxygen
Q is optionally a group of formula (III):

[0024]

Embedded image (III)

(Where D is³, D⁴, J³And J⁴Independently represent C, N, O, S and shared
A group selected from a bond, but D³, D⁴, J³And J⁴More than one of
Never O, D³, D⁴, J³And J⁴S is more than one of
Never, D³, D⁴, J³And J⁴Is O and S, then D³, D ⁴ , J³And J⁴One must be a covalent bond, and D³, D⁴, J ³ And J⁴Is not N, provided that R⁹, R¹⁰,
R¹¹, R¹²And R¹³Are each independently carbon tetravalent, nitrogen trivalent
, The divalent nature of sulfur and the divalent nature of oxygen
Q is hydride, alkyl, alkoxy, alkylamino, alk
Kirthio, haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl,
Partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl
, Cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl
Chloroalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, ha
Rocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloal
Kenyloxyalkyl, halocycloalkoxyalkyl and halocycloalkene
A group selected from the group consisting of niloxyalkyl, provided that Z⁰Is Q
K is other than a single covalent bond; K is (CR^4aR^4b)_nWherein n is an integer selected from 1-4; R^4aAnd R^4bIs independently halo, hydride, hydroxy, cyano,
Droxyalkyl, alkyl, alkenyl, aryl, aralkyl, aralkyl
Sialkyl, aryloxyalkyl, alkoxyalkyl, heteroaryl
Xyalkyl, alkenyloxyalkyl, alkylthioalkyl, aralkyl
Thioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl
, Haloalkyl, haloalkenyl, heteroaryl, heteroarylalkyl
, Heteroarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl
, Alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkyl
Rusulfinyl, arylsulfinylalkyl, arylsulfonylalkyl
, Heteroarylsulfonylalkyl, heteroarylsulfinylalkyl,
Consists of aralkylsulfinylalkyl and aralkylsulfonylalkyl
A group selected from the group wherein halo, hydroxy and cyano are present simultaneously
Are bonded to different carbons and R^4aAnd R^4bIs directly linked to the pyrimidinone nitrogen
When attached to the carbon to which it is attached, is a group other than hydroxy or cyano;

R^4aAnd R^4bIs oxo, thio, if attached to the same carbon,
And a cycloalkyl ring having 3 to 8 members, having 5 to 8 members
From the group consisting of cycloalkenyl rings, heterocyclyl rings having 5 to 8 members
Linear spacer with 2 to 7 adjacent atoms attached to form a selected ring
Used together to form a group selected from the group consisting of: ^4a And R^4bAre both when the normal carbon is directly bonded to the pyrimidinone nitrogen
E, oxo or thiono;⁰Is that K is (CR^4aR^4b)_nThen E¹, Where E¹Is a simple shared connection
In this case, O, S, C (O), C (S), C (O) O, C (S) O, C (O) S, C (
S) S, C (O) N (R⁷), (R⁷) NC (O), C (S) N (R⁷), (R ⁷ ) NC (S), OC (O) N (R⁷), (R⁷) NC (O) O, SC (S) N
(R⁷), (R⁷) NC (S) S, SC (O) N (R⁷), (R⁷) NC (O)
S, OC (S) N (R⁷), (R⁷) NC (S) O, N (R⁸) C (O) N (R ⁷ ), (R⁷) NC (O) N (R⁸), N (R⁸) C (S) N (R⁷), (R⁷ ) NC (S) N (R⁸), S (O), S (O)₂, S (O)₂N (R⁷), N (
R⁷) S (O)₂, S (O)₂N (R⁷) C (O), C (O) N (R⁷) S (O
)₂, Se, Se (O), Se (O)₂, Se (O)₂N (R⁷), N (R⁷)
Se (O)₂, P (O) (R⁸), N (R⁷) P (O) (R⁸), P (O) (R ⁸ ) N (R⁷), N (R⁷), ON (R⁷), SiR²⁸R²⁹, CR^4a= C
R^4b, Ethinylidene (C≡C; 1,2-ethylene) and C = CR^4aR^4b K is, if desired, (H (R¹⁴))_j-T, where j is selected from 0-3
T is a single covalent bond, O, S, and N (R⁷Selected from the group consisting of
Group, provided that R¹⁴Represents, when j is 1, hydroxy, cyano, halo, amido
Groups other than amino, alkylamino, dialkylaluminum and sulfhydryl, and
And (CH (R¹⁴))_jIs directly attached to the pyrimidinone ring;

E⁰Means that K is (CH (R¹⁴))_jIn the case of -T, if desired,²And here E ² Is a single covalent bond, C (O), C (S), C (O) O, C (S) O, C (O) S
, C (S) S, C (O) N (R⁷), (R⁷) NC (O), C (S) N (R⁷)
, (R⁷) NC (S), (R⁷) NC (O) O, (R⁷) NC (S) S, (R⁷ ) NC (O) S, (R⁷) NC (S) O, N (R⁸) C (O) N (R⁷), (R ⁷ ) NC (O) N (R⁸), N (R⁸) C (S) N (R⁷), (R⁷) NC (S
) N (R⁸), S (O), S (O)₂, S (O)₂N (R⁷), N (R⁷) S (
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 (R⁷) Se (O)₂, P (O
) (R⁸), N (R⁷) P (O) (R⁸), P (O) (R⁸) N (R⁷)and
N (R⁷A group selected from the group consisting of: K is G- (CH (R^Fifteen))_kHere, k is selected from 1 to 3.
The selected integer, G, is O, S and N (R⁷A group selected from the group consisting of
But R^FifteenIs, when k is 1, hydroxy, cyano, halo, amino, alkyl
A group other than amino, dialkylamino and sulfhydryl; E⁰Means that K is G- (CH (R^Fifteen))_kIf desired, E³,here
, E³Are O, S, C (O), C (S), C (O) O, C (S) O, C (O) S
, C (S) S, C (O) N (R⁷), (R⁷) NC (O), C (S) N (R⁷)
, (R⁷) NC (S), OC (O) N (R⁷), (R⁷) NC (O) O, SC (
S) N (R⁷), (R⁷) NC (S) S, SC (O) N (R⁷), (R⁷) NC
(O) S, OC (S) N (R⁷), (R⁷) NC (S) O, N (R⁸) C (O)
N (R⁷), (R⁷) NC (O) N (R⁸), N (R⁸) C (S) N (R⁷),
(R⁷) NC (S) N (R⁸), S (O), S (O)₂, S (O)₂N (R⁷)
, N (R⁷) S (O)₂, Se, Se (O), Se (O)₂, Se (O)₂N (
R⁷), N (R⁷) Se (O)₂, P (O) (R⁸), N (R⁷) P (O) (R ⁸ ), P (O) (R⁸) N (R⁷), N (R⁷), ON (R⁷), SiR²⁸R ²⁹ , CR^4a= CR^4b, Ethinylidene (C≡C; 1,2-ethynyl) and
C = CR^4aR^4bA group selected from the group consisting of: Y⁰Is represented by the formula (IV):

[0028]

Embedded image (IV)

(Where D is⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from a bond, provided that more than one is not a covalent bond but a K²Is
Independently, C and N⁺A group selected from the group consisting of⁵, D⁶, J⁵and
J⁶Is not O, and D⁵, D⁶, J⁵And J⁶Of 1
More than one cannot be S and D⁵, D⁶, J⁵And J⁶Two of O
And for S, D⁵, D⁶, J⁵And J⁶One must be a covalent bond
, And K²Is N⁺In the case of D⁵, D⁶, J⁵And J⁶More than three are N
And K²If is carbon, D⁵, D⁶, J⁵And J⁶Of 4
More than one cannot be N, provided that R¹⁶, R¹⁷, R¹⁸And R ¹⁹ Are each independently carbon tetravalent, nitrogen trivalent, sulfur divalent
A group selected so as to maintain the divalent nature of oxygen and oxygen);¹⁶And R¹⁷May optionally have independently 5 to 8 neighbors
A loalkenyl ring, a partially saturated heterocyclyl ring having 5 to 8 members,
Selected from the group consisting of heteroaryl rings and aryl having 5 to 6 members
A linear spacer moiety having from 3 to 6 adjacent atoms attached to form a ring
Used together to form; R¹⁸And R¹⁹May optionally have independently 5 to 8 neighbors
A loalkenyl ring, a partially saturated heterocyclyl ring having 5 to 8 members,
Selected from the group consisting of heteroaryl rings and aryl having 5 to 6 members
A linear spacer moiety having from 3 to 6 adjacent atoms attached to form a ring
Used together to form; Q^bIs NR²⁰R²¹,⁺NR²⁰R²¹R²², Oxy, alkyl, ami
Noalkylenyl, alkylamino, dialkylamino, dialkylsulfonium
Alkyl, acylamino and Q^beA group selected from the group consisting of ^be Is a hydride and R²⁰, R²¹And R²²Is, independently, a hydride,
Amino, alkyl, hydroxy, alkoxy, aminoalkylenyl, alkyl
A group selected from the group consisting of mino, dialkylamino and hydroxyalkyl
Where R²⁰, R²¹And R²²More than one, at the same time, hydroxy
, Alkoxy, alkylamino, amino and dialkylamino
And R²⁰, R²¹And R²²Is K²Is N⁺In the case of hydroxy, a
A group other than alkoxy, alkylamino, amino and dialkylamino;

R²⁰And R²¹, R²⁰And R²², And R²¹And R²²Is the place
If desired, the groups independently selected for spacer pair formation, where
-Serpair is a partially saturated heterocyclyl ring with 5 to 8 members
For the synthesis, it has 4 to 7 neighboring atoms that bind to the binding site of the spacer pair.
Used together to form one linear part, provided that the spacer pair R²⁰and
R²¹, R²⁰And R²², And R²¹And R²²More than one of the same
Sometimes not used; Q^bIs optionally N (R²⁶) SO₂N (R²³) (R²⁴), N (R^{2 6} ) C (O) OR⁵, N (R²⁶) C (O) SR⁵, N (R²⁶) C (S) OR ⁵ And N (R²⁶) C (S) SR⁵A group selected from the group consisting of: ²³ , R²⁴And R²⁶When two of the group consisting of are bonded to the same atom,²³ , R²⁴And R²⁶More than one is hydroxy, alkoxy, alkylene
Cannot be amino, alkylamino, amino, or dialkylamino; Q^bIs optionally a dialkylsulfonium, a trialkylphosphonium,
C (NR²⁵) NR²³R²⁴, N (R²⁶) C (NR²⁵) N (R²³) (R ²⁴ ), N (R²⁶) C (O) N (R²³) (R²⁴), N (R²⁶) C (S)
N (R²³) (R²⁴), C (NR²⁵) OR⁵, C (O) N (R²⁶) C (N
R²⁵) N (R²³) (R²⁴), C (S) N (R²⁶) C (NR²⁵) N (R ²³ ) (R²⁴), N (R²⁶) N (R²⁶) C (NR²⁵) N (R²³) (R ²⁴ ), ON (R²⁶) C (NR²⁵) N (R²³) (R²⁴), N (R²⁶)
N (R²⁶) SO₂N (R²³) (R²⁴), C (NR²⁵) SR⁵, C (O)
NR²³R²⁴And C (O) NR²³R²⁴A group selected from the group consisting of
But R²³, R²⁴And R²⁶Any two of the group consisting of
If combined, R²³, R²⁴And R²⁶More than one is hydroxy, al
Without being a oxy, alkylamino, amino, or dialkylamino,
Note Q^bThe group is directly attached to the carbon atom;²³, R²⁴, R²⁵And R²⁶Is independently hydride, alkyl,
Droxy, alkoxy, alkylenylamino, amino, alkylamino, dial
A group selected from the group consisting of killamino and hydroxyalkyl;

R²³And R²⁴Is optionally a heterocyclyl ring having from 5 to 8 members
Linear spacer with 4 to 7 adjacent atoms attached to the binding site to form
Utilized to form a part; R²³And R²⁵, R²⁴And R²⁵, R²⁵And R²⁶, R²⁴And
And R²⁶And R²³And R²⁶Are, independently, optionally, spacer pairs
Where the spacer pair forms an LUV group
Selected from the binding sites of the selected spacer pair, where L, U
And V are independently O, S, C (O), C (S), C (J_H)₂S (O),
S (O)₂, OP (OR³¹) R³⁰, P (O) R³⁰, P (S) R³⁰, C (
R³⁰) R³¹, C = C (R³⁰) R³¹, (O)₂POP (O)₂, R³⁰(
O) POP (O) R³⁰, Si (R²⁹) R²⁸, Si (R²⁹) R²⁸Si (
R²⁹) R²⁸, Si (R²⁹) R²⁸OSi (R²⁹) R²⁸, (R²⁸) R ²⁹ COC (R²⁸) R²⁹, (R²⁸) R²⁹CSC (R²⁸) R²⁹, C (
O) C (R³⁰) = C (R³¹), C (S) C (R³⁰) = C (R³¹), S (
O) C (R³⁰) = C (R³¹), SO₂C (R³⁰) = C (R³¹), PR^{3 0} C (R³⁰) = C (R³¹), P (O) R³⁰C (R³⁰) = C (R³¹),
P (S) R³⁰C (R³⁰) = C (R³¹), DC (R³⁰) (R³¹) D, O
P (R³¹) R³⁰, P (O) R³⁰, P (S) R³⁰, Si (R²⁸) R²⁹ And N (R³⁰), And a group selected from the group consisting of
, U and V are not the same covalent bond, and
And the heterocyclyls characterized by L, U and V have 5 to 10 close members
D is oxygen, C = O, C = S, S (O)_mA group selected from the group consisting of
Wherein m is an integer selected from 0 to 2;_HIs independently OR²⁷, SR²⁷And N (R²⁰) R²¹Group consisting of
A group selected from;

R ²⁷ is hydride, 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,
Selected from the group consisting of heteroarylthioalkyl, heteroaralkylthioalkyl, arylsulfinylalkyl, arylsulfonylalkyl, cycloalkylsulfinylalkyl, cycloalkylsulfonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl and aralkylsulfonylalkyl R ³⁰ and R ³¹ are independently hydride, hydroxy, thiol, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl,
Heteroaryloxyalkyl, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxy Alkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, haloaralkylsulfinylalkyl, Aralkylsulfonylalkyl, cyanoalkyl, dicyanoalkyl Carboxamidoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyl, carboalkoxyalkyl, dicarboalkoxyalkyl, cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl, dicarboxamidocycloalkyl, carboalkoxycyanocycloalkyl, carboalkoxy Cycloalkyl, dicarboalkoxycycloalkyl, formylalkyl, acylalkyl, dialkoxyphosphonoalkyl, dialalkoxyphosphonoalkyl, phosphonoalkyl, dialkoxyphosphonoalkoxy, dialalkoxyphosphonoalkoxy, phosphonoalkoxy,
Dialkoxyphosphonoalkylamino, dialalkoxyphosphonoalkylamino, phosphonoalkylamino, dialkoxyphosphonoalkyl, dialalkoxyphosphonoalkyl, sulfonylalkyl, alkoxysulfonylalkyl, aralkoxysulfonylalkyl, alkoxysulfonylalkoxy, A group selected from the group consisting of aralkoxysulfonylalkoxy, sulfonylalkoxy, alkoxysulfonylalkylamino, aralkoxysulfonylalkylamino, and sulfonylalkylamino;

R³⁰And R³¹Is optionally a cycloalkyl having 3 to 8 adjacent atoms
Ring, a cycloalkenyl ring having 3 to 8 adjacent atoms, and 3 to 8 adjacent atoms.
Bond to form a ring selected from the group consisting of heterocyclyl rings with
Used together to form a straight chain with 2 to 7 adjacent atoms; R²³And R²⁵, R²⁴And R²⁵, R²⁵And R²⁶, R²⁴And
And R²⁶, And R²³And R²⁶Can, if desired, be independently
Where the spacer pair forms an LUV group.
Selected from the binding sites of the spacer pair selected to form, where L,
U and V are independently a cycloalkyl radical, a cycloalkenyl radical
Where the cycloalkyl and cycloalkenyl radicals are R³⁰And R ³¹ A group substituted by one or more of the group consisting of: an aryl radical;
Low aryl radicals, saturated heterocyclic radicals and partially saturated heterosa
A group selected from the group of 1,2-substituted radicals
Here, the 1,2-substituents are independently C ＝ O, C ＝ S, C (R²⁸) R³² , S (O), S (O)₂, OP (OR³¹) R³⁰, P (O) R³⁰, P (S)
R³⁰And Si (R²⁸) R²⁹A group selected from the group consisting of: R²³And R²⁵, R²⁴And R²⁵, R²⁵And R²⁶, R²⁴And
And R²⁶, And R²³And R²⁶Can, if desired, be independently
Where the spacer pair forms an LUV group.
Selected from the binding sites of the spacer pair selected to form, where L,
U and V are independently 1,2-substituted alkylene radicals and 1,2-2
A group selected from substituted alkenylene radicals, wherein the 1,2-substituent is
Independently, C = O, C = S, C (R²⁸) R²⁹, S (O), S (O)₂, OP
(OR³¹) R³⁰, P (O) R³⁰, P (S) R³⁰And Si (R²⁸) R ²⁹ And a group selected from the group consisting of
Zikaru is R³⁰Or R³¹A group that is substituted on one or more of the substituents;

Q^sIs a single covalent bond, (CR³⁷R³⁸)_b− (W⁰)_az, Where az is
An integer selected from 0 to 1; b is an integer selected from 1 to 4;⁰Is O, S
, C (O), C (S), C (O) O, C (S) O, C (O) S, C (S) S, C
(O) N (R¹⁴), (R¹⁴) NC (O), C (S) N (R¹⁴), (R¹⁴ ) NC (S), OC (O) N (R¹⁴), SC (S) N (R¹⁴), SC (O)
N (R¹⁴), OC (S) N (R¹⁴), N (R^Fifteen) C (O) N (R¹⁴),
(R¹⁴) NC (O) N (R^Fifteen), N (R^Fifteen) C (S) N (R¹⁴), (R ¹⁴ ) NC (S) N (R^Fifteen), S (O), S (O)₂, S (O)₂N (R¹⁴ ), N (R¹⁴) S (O)₂, Se, Se (O), Se (O)₂, Se (O)₂ N (R¹⁷), N (R¹⁴) Se (O)₂, P (O) (R⁸), N (R⁷) P (
O) (R⁸), P (O) (R⁸) N (R⁷), N (R¹⁴), ON (R¹⁴)
And SiR²⁸R²⁹A group selected from the group consisting of (CH (R¹⁴))_c-W ¹ -(CH (R^Fifteen))_dWherein c and d are independently selected from 1-4
Integer, W¹Are O, S, C (O), C (S), C (O) O, C (S) O,
C (O) S, C (S) S, C (O) N (R¹⁴), (R¹⁴) NC (O), C (
S) N (R¹⁴), (R¹⁴) NC (S), OC (O) N (R¹⁴), (R¹⁴ ) NC (O) O, SC (S) N (R¹⁴), (R¹⁴) NC (S) S, SC (O
) N (R¹⁴), (R¹⁴) NC (O) S, OC (S) N (R¹⁴), (R¹⁴ ) NC (S) O, N (R^Fifteen) C (O) N (R¹⁴), (R¹⁴) NC (O) N
(R^Fifteen), N (R^Fifteen) C (S) N (R¹⁴), (R¹⁴) NC (S) N (R ^Fifteen ), S (O), S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴) S (O
)₂, Se, Se (O), Se (O)₂, Se (O)₂N (R¹⁴), N (R^{1 4} ) Se (O)₂, P (O) (R⁸), N (R⁷) P (O) (R⁸), P (O)
(R⁸) N (R⁷), N (R¹⁴), ON (R¹⁴), And SiR²⁸R²⁹ And a group selected from the group consisting of¹⁴))_e-W²²− (CH (
R^Fifteen))_hWherein e and h are independently selected from the group consisting of:
An integer selected from 0 to 2, and W²²Is CR⁴¹= CR⁴², CR⁴¹R ⁴² = C; vinylidene), ethinylidene (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-morpholine
Linyl, 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
Peridinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl
Nil, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,
3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydro
Furanyl, 2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuran
A group selected from the group consisting of¹⁴And R^FifteenIs directly bonded to N
A group selected from groups other than halo and cyano, and (CR³⁷R^{3 8} )_b, (CH (R¹⁴))_cAnd (CH (R¹⁴))_eIs E⁰Join to
;

R³⁷And R³⁷Is optionally 3-8 when attached to different carbons
A cycloalkyl ring having a proximity member, a cycloalkenyl ring having 3 to 8 proximity members,
Forming a ring selected from the group consisting of heterocyclyl rings having 3 to 8 members
Used together to form a linear spacer moiety having 1 to 7 adjacent atoms
R³⁷And R³⁸Has 3 to 8 neighbors when attached to different carbons
Cycloalkyl ring, cycloalkenyl ring having 3 to 8 members, 3 to 8 members
Near 1 to 7 forming a ring selected from the group consisting of heterocyclyl rings with members
Used together to form a linear spacer moiety with tangent atoms; R³⁸And R³⁸Has 3 to 8 neighbors when attached to different carbons
Cycloalkyl ring, cycloalkenyl ring having 3 to 8 members, 3 to 8 members
Near 1 to 7 forming a ring selected from the group consisting of heterocyclyl rings with members
Used together to form a linear spacer moiety with tangent atoms; R³⁷And R³⁸Are oxo, thiono, and alkyl when attached to the same carbon.
Len, haloalkylene and a cycloalkyl ring having 3 to 8 members, 3 to 8
Cycloalkenyl ring with three members, heterocyclyl with three to eight members
Two to seven adjacent atoms selected to form a ring selected from the group consisting of rings
Used together to form a group selected from the linear spacer moiety possessed; Y⁰Is optionally Q^b−Q^ss, Where Q^ssIs (CR³⁷R³⁸) _f , Where f is an integer selected from 1 to 6, (CH (R¹⁴))_c-W¹−
(CH (R^Fifteen))_dWhere c and d are independently selected from 1-4.
Integer, W¹Are O, S, C (O), C (S), C (O) O, C (S) O, C (
O) S, C (S) S, C (O) N (R¹⁴), (R¹⁴) NC (O), C (S)
N (R¹⁴), (R¹⁴) NC (S), OC (O) N (R¹⁴), (R¹⁴) N
C (O) O, SC (S) N (R¹⁴), (R¹⁴) NC (S) S, SC (O) N
(R¹⁴), (R¹⁴) NC (O) S, OC (S) N (R¹⁴), (R¹⁴) N
C (S) O, N (R^Fifteen) C (O) N (R¹⁴), (R¹⁴) NC (O) N (R ^Fifteen ), N (R^Fifteen) C (S) N (R¹⁴), (R¹⁴) NC (S) N (R^Fifteen ), S (O), S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴) S (O)₂ , Se, Se (O), Se (O)₂, Se (O)₂N (R¹⁴), N (R¹⁴)
Se (O)₂, P (O) (R⁸), N (R⁷) P (O) (R⁸), P (O) (R ⁸ ) N (R⁷), N (R¹⁴), ON (R¹⁴), And SiR²⁸R²⁹From
And a group selected from the group consisting of¹⁴))_e-W²-(CH (R^Fifteen ))_hA group selected from the group consisting of: wherein e and h are independently 0-2
An integer selected from and W²Is CR^4a= CR^4b, Ethinylidene (C≡
C; 1,2-ethynyl), and C = CR^4aR^4bSelected from the group consisting of
Group, where R¹⁴And R^FifteenIs halo and cyano when directly bonded to N
A group selected from groups other than³⁷R³⁸)_f, (CH (R^Fifteen)) _c And (CH (R^Fifteen))_eIs E⁰And Q^bIs Q^ssIs (CR^{3 7} R³⁸)_f, Where f is other than 1 and N (R²⁶) N (R²⁶) C (NR ²⁵ ) N (R²³) (R²⁴) Or ON (R²⁶) C (NR²⁵) N (R²³ ) (R²⁴) Is selected from groups other than;

Y ⁰ is, if desired, Q ^b -Q ^sss , where Q ^sss is (CH (R ³⁸ )) _r -W ³ , r is an integer selected from 1 to ³ , and W ³ is 1,1,1-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-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
-On-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,
Selected from the group consisting of 3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl and 3,5-tetrahydropyranyl is the group and each ring carbon and hydride-containing nitrogen W ³ other than the binding site, may ^{optionally, R 9, R 1 0,} R 11 and optionally substituted by R ¹² at one or more of the group consisting Where (CH (R ³⁸ )) _r is attached to E ⁰ and Q ^b is attached to the position with the least number of substituents on each W ³ ;

[0037] Y⁰Is optionally Q^b−Q^sssr, Where Q^sssrIs (CH (R ³⁸ ))_r-W⁴, R is an integer selected from 1 to 3, W⁴Is 1,2-cyclo
Butyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl
Sil, 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-piperazi
Nil, 1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,
6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl
Lysinyl, 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, 2,
H-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-te
Trahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuran
2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-
Tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetrahydropyran
A group selected from the group consisting of lanyl and 3,5-tetrahydropyranyl, and
And W other than the binding site⁴The ring carbon and the hydride-containing nitrogen of⁹ , R¹⁰, R¹¹And R¹²Replaced by one or more of the group consisting of:
Provided that (CH (R³⁸))_rIs E⁰And Q^bIs each W ⁴ Binds to the highest substituent of

[0038] Y⁰Is optionally Q^b−Q^ssss, Where Q^ssssIs (CH (R ³⁸ ))_r-W⁵, R is an integer selected from 1 to 3, W⁵Is 1,4-ind
Nyl, 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-i
Ndenyl, 2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzo
Furanyl, 2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzo
Furanyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzo
Thiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2
, 7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothio
Phenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4
-Imidazo (1,2-a) pyridinyl, 2,5-imidazo (1,2-a) pyridinyl
Nil, 2,6-imidazo (1,2-a) pyridinyl, 2,7-imidazo (1,2
-A) pyridinyl, 3,4-imidazo (1,2-a) pyridinyl, 3,5-imi
Dazo (1,2-a) pyridinyl, 3,6-imidazo (1,2-a) pyridinyl,
3,7-imidazo (1,2-a) pyridinyl, 2,4-indolyl, 2,5-i
Drill, 2,6-in drill, 2,7-in drill, 3,4-in drill, 3
, 5-Indolyl, 3,6-Indolyl, 3,7-Indolyl, 1,4-Isoyl
Drill, 1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl
Drill, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl
Drill, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazo
Ryl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazoly
2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxy
Sazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3
, 6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthy
1,1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl
2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl
2,2-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinyl
Nolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl, 3
, 5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl
Nil, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8
-Quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-i
Soquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-i
Soquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-i
Soquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-i
Soquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cy
Nonlinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolin
Nil, 3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl,
A group selected from the group consisting of 4,7-cinnolinyl and 4,8-cinnolinyl
, And W⁵The ring carbon and the hydride-containing nitrogen of⁹, R^{1 0} , R¹¹And R¹²May be substituted with one or more of the group consisting of
Yes, but Q^bIs each W⁵At the position having the least number of substituents, and (C
H (R³⁸))_rIs E⁰Binds to

Y ⁰ may be Q ^b -Q ^ssssr , where desired, where Q ^{sss sr} is (CH (R ³⁸ )) _r -W ⁶ , where r is selected from 1-3 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-benzofuranyl, 2, 7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothio Phenyl, 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-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-isoindolyl, 2,5- 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 1,3,7-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-cinnolinyl, 4,
The group selected from the group consisting of 6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl, and the carbon and hydride-containing nitrogen of the ring of W ⁶ may optionally be R ⁹ , R ¹⁰ , R ¹¹ and One or more of the group consisting of R ¹² may be substituted, provided that Q ^b is attached at the position with the highest number of substituents on each W ⁶ and (CH (R ³⁸ )) _r a variety of prevention of symptoms of thrombosis and treatment to anticoagulant therapy useful substituted polycyclic aryl and heteroaryl pyrimidinone including coronary artery and cerebrovascular disease represented by] binding to E ⁰ It relates to a group of compounds characterized by nonone or a pharmaceutically acceptable salt thereof.

Specific examples of the compound of formula (I) or a pharmaceutically acceptable salt thereof are: J is selected from the group consisting of O and S; J is CH-R ⁶ and group selected from the group consisting of ^{N-R 6,}
Here, R ⁶ is R ^4a to form a heterocyclyl ring having 5 to 8 members,
A linear spacer portion having a chain length of 1-4 atoms bonded to a binding site of a substituent selected from the group consisting of R ^4b , R ³⁹ , R ⁴⁰ , R ⁵ , R ¹⁴ and R ¹⁵ ; (V):

[0041]

Embedded image (V)

(Wherein; D¹, D², J¹, J²And K¹Independently represent C, N, O, S and
And a group selected from the group consisting of:
There is no, D¹, D², J¹, J²And K¹More than one is O
Never, D¹, D², J¹, J²And K¹S is more than one of
Never, D¹, D², J¹, J²And K¹Is O and S, then D ¹ , D², J¹, J²And K¹One must be a covalent bond, and
D¹, D², J¹, J²And K¹More than four cannot be N
But R³², R³³, R³⁴, R³⁵And R³⁶Are each independently a carbon
Maintain tetravalent properties, nitrogen trivalent properties, sulfur divalent properties, and oxygen divalent properties.
Selected to have a group represented by:

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 hydride, acetamido, haloacetamide, amidino, guanidino, dialkylsulfonium,
Trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhalo Aralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroaryl Amino-N-alkylamino, heteroarylamino Alkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxy kill shea alkyl, heteroaralkoxy,
Cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino,
Alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, hetero Arylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamide,
Alkylaminosulfonyl, amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamide, diarylamidosulfonyl, monoalkylmonoarylamidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio,
Heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralcanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalkyl,
Alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,
Hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, alkenylamino, hydroxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxy Alkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,
Carboalkoxy, alkoxycarboxamide, alkylamidocarbonylamide, arylamidocarbonylamide, carboalkoxyalkyl, carboalkoxyalkenyl, carboxy, carboaralkoxy, carboxamide, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl , A group selected from the group consisting of dialalkoxyphosphono and dialalkoxyphosphonoalkyl;

R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵And R³⁶Is optional
And independently Q^bWhere R¹⁶And R¹⁹More than one at the same time Q ^b Is not, Q^bIs Q^beR³²And R³³, R³³And R³⁴, R³⁴And R³⁵, And R^{3 5} And R³⁶Are optionally selected to form a spacer pair independently.
The selected group, wherein the spacer pair is a cycloalkane having 5 to 8 members
Nyl ring, partially saturated heterocyclyl ring having 5 to 8 members, 5 to 6
Of a ring selected from the group consisting of heteroaryl rings and aryls having adjacent members of
Having three to six adjacent atoms that bind to the binding site of the spacer pair for formation.
Used together to form one linear part, provided that the spacer pair R³²And
And R³³, R³³And R³⁴, R³⁴And R³⁵, And R³⁵And R^{3 6} No more than one is used simultaneously; R⁹And R¹⁰, R¹⁰And R¹¹, R¹¹And R¹², And R¹² And R¹³Are, optionally, independently selected for spacer pair formation.
Wherein the spacer pair is a cycloalkenyl ring having 5 to 8 close members,
Partially saturated heterocyclyl ring with 5 to 8 members, 5 to 6 members
Forming a ring selected from the group consisting of a heteroaryl ring and an aryl having
For example, a linear chain having 3 to 6 adjacent atoms bonded to the binding site of the spacer pair
Used together to form a part, except that the spacer pair R⁹And R¹⁰,
R¹⁰And R¹¹, R¹¹And R¹², And R¹²And R¹³One of
More are not used at the same time;

B is hydride, trialkyl, C2-C8 alkyl, C3-C
A group selected from the group consisting of 8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, C2-C8 haloalkyl and C3-C8 haloalkenyl, wherein each member of B is optionally a binding site for B to A B may be optionally substituted with one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ ; C3-C15 cycloalkyl, C5-C10 cycloalkenyl, C4-C12 saturated heterocyclyl, and C4-C9 moiety group selected from the group consisting of saturated heterocyclyl, wherein each ring carbon is ^optionally substituted with ^{R 33} And any ring carbon including a ring carbon other than the ring carbon of the bonding site of B to A is optionally substituted with oxo. Wherein the ring carbon and nitrogen adjacent to the carbon atom at the point of attachment, where no more than one ring carbon is simultaneously substituted with oxo, are optionally substituted with R ⁹ and R ¹³ The ring carbon or nitrogen atom adjacent to the R ⁹ position and 2 atoms away from the bonding site may be optionally substituted with R ^10, and may be substituted at the R ¹³ position with 2 atoms from the bonding site.
A ring carbon or nitrogen atom remote from the atom may be optionally substituted with R ¹² , and a ring carbon or nitrogen atom adjacent to the R ¹⁰ position 3 atoms away from the bonding site is
Optionally, a ring carbon or nitrogen atom adjacent to R ¹² which is 3 atoms away from the bonding site and which may be substituted with R ¹¹ may be optionally substituted with R ³³ and 4 atoms from the bonding site A remote ring carbon or nitrogen atom adjacent to R ¹¹ and R ³³ may be optionally substituted with R ³⁴ ;

A represents a single covalent bond and (W⁷)_rr-(CH (R^Fifteen))_paAnd (C
H (R^Fifteen))_pa− (W⁷)_rrA group selected from the group consisting of
Is an integer selected from 0 to 1, pa is an integer selected from 0 to 6, and W ⁷ Are O, S, C (O), C (S), C (O) S, C (S) O, C (O) N (R ⁷ ), C (S) N (R⁷), (R⁷) NC (O), (R⁷) NC (S), S (O
), S (O)₂, S (O)₂N (R⁷), (R⁷) NS (O)₂, P (O) (R ⁸ ), N (R⁷) P (O) (R⁸), P (O) (R⁸) N (R⁷), C (NR⁷ ) N (R⁷), (R⁷) NC (NR⁷), (R⁷) NC (NR⁷) NR⁷and
N (R⁷A group selected from the group consisting of rr and pa
No more than one can be zero at the same time; R⁷And R⁸Is independently hydride, hydroxy, alkyl, acyl,
A group selected from the group consisting of royl, heteroaroyl and alkoxyalkyl
R¹⁴, R^Fifteen, R³⁷And R³⁸Is independently hydride, hydroxy,
Halo, cyano, hydroxyalkyl, alkoxy, alkyl, alkoxyalkyl
, Cycloalkyl, cycloalkylalkyl, silk alkenyl, cycloal
Kenylalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkco
Xyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halosi
Chloroalkoxyalkyl, halocycloalkenyloxyalkyl, carboxy,
Carboxyalkyl, carboalkoxy, carboxamide and carboxyl
A group selected from the group consisting of a midalkyl; R¹⁴And R³⁸Is independently acyl, aroyl, and heteroaroyl
A group selected from the group consisting of: wherein acyl is formyl and 2-oxoa
Is selected from groups other than sil;⁵, O, C (O), C (S), S, S (O), S (O)₂, ON (
R⁵), P (O) (R⁸) And CR³⁹R⁴⁰A group selected from the group consisting of: R⁵Is hydride, hydroxy, amino, alkyl, alkoxy, alkoxy
The group consisting of alkyl, haloalkyl, acyl, aroyl, and heteroaroyl
A group selected from: R³⁹And R⁴⁰Is independently hydride, hydroxy, halo, cyano,
Droxyalkyl, acyl, aroyl, heteroaroyl, acylamide, alcohol
Xy, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, haloa
Alkoxyalkyl, alkylsulfonyl, haloalkylsulfonyl, carboxy
, Carboxyalkyl, carboalkoxy, carboxamide and carboxy
A group selected from the group consisting of amidoalkyl;

M is N and R¹A group selected from the group consisting of: -C; R²And R¹Is independently Z⁰-Q, hydride, alkyl, alkenyl and
R is a group selected from the group consisting of:¹Is optionally amino, aminoalkyl, alkylamino, amidino,
Guanidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl
, Alkoxyamino, thiol, alkylthio, dialkylsulfonium, tri
Alkylphosphonium, dialkylsulfoniumalkyl, heteroarylamido
No, nitro, arylamino, aralkylamino, alkanoyl, alkenoyl
, Aroyl, heteroaroyl, aralcanoyl, heteroaralkanoyl, haloa
From the group consisting of lucanoyl, hydroxyhaloalkyl, cyano, and phosphono
Group selected; Z⁰Is a single covalent bond and (CR⁴¹R⁴²)_q, Where q is 1-6
An integer selected from (CH (R⁴¹)_g-W⁰-(CH (R⁴²))_p,here
, G and p are independently an integer selected from 0 to 3, W⁰Are O, S, C (
O), C (S), C (O) O, C (S) O, C (O) S, C (S) S, C (O)
N (R⁴¹), (R⁴¹) NC (O), C (S) N (R⁴¹), (R⁴¹) NC
(S), OC (O) N (R⁴¹), (R⁴¹) NC (O) O, SC (S) N (R ⁴¹ ), (R⁴¹) NC (S) S, SC (O) N (R⁴¹), (R⁴¹) NC (
O) S, OC (S) N (R⁴¹), (R⁴¹) NC (S) O, N (R⁴²) C (
O) N (R⁴¹), (R⁴¹) NC (O) N (R⁴²), N (R⁴²) C (S)
N (R⁴¹), (R⁴¹) NC (S) N (R⁴²), S (O), S (O)₂, S
(O)₂N (R⁴¹), N (R⁴¹) S (O)₂, Se, Se (O), Se (O
)₂, Se (O)₂N (R⁴¹), N (R⁴¹) Se (O)₂, P (O) (R⁸ ), N (R⁷) P (O) (R⁸), P (O) (R⁸) N (R⁷), N (R⁴¹)
, ON (R⁴¹) And SiR²⁸R²⁹A group selected from the group consisting of:
(CH (R⁴¹))_e-W²²-(CH (R⁴²))_hGroup selected from here
Where h is an integer selected from 0 to 2;²²Is CR⁴¹= CR⁴², R⁴¹ R⁴²= C; vinylidene), ethinylidene (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-morph
Folinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazini
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-pyrrolidyl
Dinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl
, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrid
Lofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydrofurani
A group selected from the group consisting of⁴¹And R⁴²Is directly bonded to N
A group selected from groups other than halo and cyano, and Z⁰Is the pirimi
Directly attached to the dinone ring;

R ⁴¹ and R ⁴² are independently amidino, hydroxyamino, hydride,
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, halocyclo Alkoxyalkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl Heteroaryl, heteroaralkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfonyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfonyl and Q is a group selected from the group consisting of aralkylsulfonylalkyl;

[0049]

Embedded image (II)

Where D¹, D², J¹, J²And K¹Independently represent C, N, O, S and
And a group selected from the group consisting of:
There is no, D¹, D², J¹, J²And K¹More than one is O
Never, D¹, D², J¹, J²And K¹S is more than one of
Never, D¹, D², J¹, J²And K¹Is O and S, then D ¹ , D², J¹, J²And K¹One must be a covalent bond, and
D¹, D², J¹, J²And K¹More than four cannot be N
But R⁹, R¹⁰, R¹¹, R¹²And R¹³Is each independently 4 carbon atoms
Maintains trivalent nature of nitrogen, trivalent nature of sulfur, divalent nature of sulfur and divalent nature of oxygen
Q is optionally selected from a group represented by the formula (III):

[0051]

Embedded image (III)

[Wherein D³, D⁴, J³And J⁴Independently represent C, N, O, S and shared
A group selected from a bond, but D³, D⁴, J³And J⁴More than one of
Never O, D³, D⁴, J³And J⁴S is more than one of
Never, D³, D⁴, J³And J⁴Is O and S, then D³, D ⁴ , J³And J⁴One must be a covalent bond, and D³, D⁴, J ³ And J⁴Is not N, provided that R⁹, R¹⁰,
R¹¹, R¹²And R¹³Are each independently carbon tetravalent, nitrogen trivalent
, The divalent nature of sulfur and the divalent nature of oxygen
Q is a hydride, an alkyl, an alkoxy, an alkylamino, an alk
Kirthio, haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl,
Partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl
, Cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl
Chloroalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, ha
Rocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloal
Kenyloxyalkyl, halocycloalkoxyalkyl and halocycloalkene
A group selected from the group consisting of niloxyalkyl, provided that Z⁰Is Q
Is a group other than a single covalent bond; K is (CR^4aR^4b)_nWhere n is an integer selected from 1-2.
Number; R^4aAnd R^4bIs independently halo, hydride, hydroxy, cyano,
Droxyalkyl, alkyl, alkenyl, alkoxyalkyl, aralkyl,
Heteroaralkyl, alkylthioalkyl, haloalkyl, haloalkenyl and
A group selected from the group consisting of:⁰Is that K is (CR^4aR^4b)_nThen E¹, Where E¹Is a simple shared connection
In this case, O, S, C (O), C (S), C (O) O, C (S) O, C (O) S, C (
S) S, C (O) N (R⁷), (R⁷) NC (O), C (S) N (R⁷), (R ⁷ ) NC (S), OC (O) N (R⁷), (R⁷) NC (O) O, SC (S) N
(R⁷), (R⁷) NC (S) S, SC (O) N (R⁷), (R⁷) NC (O)
S, OC (S) N (R⁷), (R⁷) NC (S) O, N (R⁸) C (O) N (R ⁷ ), (R⁷) NC (O) N (R⁸), N (R⁸) C (S) N (R⁷), (R⁷ ) NC (S) N (R⁸), S (O), S (O)₂, S (O)₂N (R⁷), N (
R⁷) S (O)₂, S (O)₂N (R⁷) C (O), C (O) N (R⁷) S (O
)₂, P (O) (R⁸), N (R⁷) P (O) (R⁸), P (O) (R⁸) N (
R⁷), N (R⁷), ON (R⁷), CR^4a= CR^4b, Ethinylidene (C≡
C; 1,2-ethynyl) and C = CR^4aR^4bA group selected from the group consisting of
;

K is optionally (H (R¹⁴))_j-T, where j is selected from 0 to 2
T is a single covalent bond, O, S, and N (R⁷Selected from the group consisting of
A group represented by the formula (CH (R¹⁴))_jIs directly attached to the pyrimidinone ring; E⁰Means that K is (H (R¹⁴))_jIn the case of -T, if desired,², Where E ² Is a single covalent bond, C (O), C (S), C (O) O, C (S) O, C (O) S
, C (S) S, C (O) N (R⁷), (R⁷) NC (O), C (S) N (R⁷)
, (R⁷) NC (S), (R⁷) NC (O) O, (R⁷) NC (S) S, (R⁷ ) NC (O) S, (R⁷) NC (S) O, N (R⁸) C (O) N (R⁷), (R ⁷ ) NC (O) N (R⁸), N (R⁸) C (S) N (R⁷), (R⁷) NC (S
) N (R⁸), S (O), S (O)₂, S (O)₂N (R⁷), N (R⁷) S (
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
(R⁷A group selected from the group consisting of: K is G- (CH (R^Fifteen))_kWhere k is selected from 1-2
The selected integer, G, is O, S and N (R⁷A group selected from the group consisting of
But R^FifteenIs, when k is 1, hydroxy, cyano, halo, amino, alkyl
A group other than amino, dialkylamino and sulfhydryl; E⁰Is G- (CH (R^Fifteen))_kIf desired, E³, Where E³ Is a single covalent bond, O, S, C (O), C (S), C (O) O, C (S) O, C (
O) S, C (S) S, C (O) N (R⁷), (R⁷) NC (O), C (S) N (
R⁷), (R⁷) NC (S), OC (O) N (R⁷), (R⁷) NC (O) O,
SC (S) N (R⁷), (R⁷) NC (S) S, SC (O) N (R⁷), (R⁷ ) NC (O) S, OC (S) N (R⁷), (R⁷) NC (S) O, N (R⁸) C
(O) N (R⁷), (R⁷) NC (O) N (R⁸), N (R⁸) C (S) N (R ⁷ ), (R⁷) NC (S) N (R⁸), S (O), S (O)₂, S (O)₂N (
R⁷), N (R⁷) S (O)₂, P (O) (R⁸), N (R⁷) P (O) (R⁸ ), P (O) (R⁸) N (R⁷), N (R⁷), ON (R⁷), CR^4a= CR ^4b , Ethinylidene (C≡C; 1,2-ethynyl) and CＣCR^4aR^4bOr
A group selected from the group consisting of: Y⁰Is represented by the formula (IV):

[0054]

Embedded image (IV)

[Wherein D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from a bond, provided that more than one is not a covalent bond but a K²Is
Independently, C and N⁺A group selected from the group consisting of⁵, D⁶, J⁵and
J⁶Is not O, and D⁵, D⁶, J⁵And J⁶Of 1
More than one cannot be S and D⁵, D⁶, J⁵And J⁶Two of O
And for S, D⁵, D⁶, J⁵And J⁶One must be a covalent bond
, And K²Is N⁺In the case of D⁵, D⁶, J⁵And J⁶More than three are N
And K²If is carbon, D⁵, D⁶, J⁵And J⁶Of 4
More than one cannot be N, provided that R¹⁶, R¹⁷, R¹⁸And R ¹⁹ Are each independently, each independently a carbon tetravalent property, a nitrogen trivalent property,
Selected to maintain the divalent nature of sulfur and the divalent nature of oxygen]
Group; R¹⁶And R¹⁷May optionally have independently 5 to 8 neighbors
A loalkenyl ring, a partially saturated heterocyclyl ring having 5 to 8 members,
Selected from the group consisting of heteroaryl rings and aryl having 5 to 6 members
A linear spacer moiety having from 3 to 6 adjacent atoms attached to form a ring
Used together to form; Q^bIs NR²⁰R²¹,⁺NR²⁰R²¹R²², Oxy, alkyl, ami
Noalkylenyl, alkylamino, dialkylamino, dialkylsulfonium
Alkyl, acylamino and Q^beSelected from the group consisting of^{b e} Is a hydride and R²⁰, R²¹And R²²Are, independently, hydride,
Mino, alkyl, hydroxy, alkoxy, aminoalkylenyl, alkylamino
No, a group selected from the group consisting of dialkylamino and hydroxyalkyl,
Where R²⁰, R²¹And R²²More than one is simultaneously a hydroxy,
Never be alkoxy, alkylamino, amino and dialkylamino
, And R²⁰, R²¹And R²²Is K²Is N⁺In the case of hydroxy, al
Groups other than coxy, alkylamino, amino and dialkylamino;

R²⁰And R²¹, R²⁰And R²², And R²¹And R²²Is the place
If desired, the groups independently selected for spacer pair formation, where
-Serpair is a partially saturated heterocyclyl ring with 5 to 8 members
For the synthesis, it has 4 to 7 neighboring atoms that bind to the binding site of the spacer pair.
Used together to form one linear part, provided that the spacer pair R²⁰and
R²¹, R²⁰And R²², And R²¹And R²²More than one of the same
Sometimes not used; Q^bIs optionally N (R²⁶) SO₂N (R²³) (R²⁴), N (R^{2 6} ) C (O) OR⁵, N (R²⁶) C (O) SR⁵, N (R²⁶) C (S) OR ⁵ And N (R²⁶) C (S) SR⁵A group selected from the group consisting of: ²³ , R²⁴And R²⁶When two of the group consisting of are bonded to the same atom,^{2 3} , R²⁴And R²⁶More than one is hydroxy, alkoxy, alkyl
Cannot be amino, amino, and dialkylamino; Q^bIs optionally, a silalkylsulfonium, a trialkylphosphonium, a C
(NR²⁵) NR²³R²⁴, N (R²⁶) C (NR²⁵) N (R²³) (R^{2 4} ), N (R²⁶) C (O) N (R²³) (R²⁴), N (R²⁶) C (S) N
(R²³) (R²⁴), C (NR²⁵) OR⁵, C (O) N (R²⁶) C (NR ²⁵ ) N (R²³) (R²⁴), C (S) N (R²⁶) C (NR²⁵) N (R^{2 3} ) (R²⁴), N (R²⁶) N (R²⁶) C (NR²⁵) N (R²³) (R^{2 4} ), ON (R²⁶) C (NR²⁵) N (R²³) (R²⁴), N (R²⁶) N
(R²⁶) SO₂N (R²³) (R²⁴), C (NR²⁵) SR⁵, C (O) N
R²³R²⁴And C (O) R²³R²⁴A group selected from the group consisting of
, R²³, R²⁴And R²⁶Any two of the groups consisting of are bonded to the same atom
If you do²³, R²⁴And R²⁶More than one is hydroxy, alcohol
Cannot be xy, alkylamino, amino, or dialkylamino; ^b The group is directly attached to the carbon atom;²³, R²⁴, R²⁵And R²⁶Is independently hydride, alkyl,
Droxy, alkoxy, aminoalkylenyl, alkylamino, dialkylamido
A group selected from the group consisting of noamino and hydroxyalkyl;

R²³And R²⁴Is optionally a heterocyclyl ring having from 5 to 8 members
Linear spacer with 4 to 7 adjacent atoms attached to the binding site to form
Used to form parts; Q^sIs a single covalent bond, (CR³⁷R³⁸)_b− (W⁰)_az, Where az is
An integer selected from 0 to 1; b is an integer selected from 1 to 4;⁰Is O, S
, C (O), C (S), C (O) O, C (S) O, C (O) S, C (S) S, C
(O) N (R¹⁴), (R¹⁴) NC (O), C (S) N (R¹⁴), (R¹⁴ ) NC (S), OC (O) N (R¹⁴), SC (S) N (R¹⁴), SC (O)
N (R¹⁴), OC (S) N (R¹⁴), N (R^Fifteen) C (O) N (R¹⁴),
(R¹⁴) NC (O) N (R^Fifteen), N (R^Fifteen) C (S) N (R¹⁴), (R ¹⁴ ) NC (S) N (R^Fifteen), S (O), S (O)₂, S (O)₂N (R¹⁴ ), N (R¹⁴) S (O)₂, P (O) (R⁸), N (R⁷) P (O) (R⁸)
, P (O) (R⁸) N (R⁷), N (R¹⁴), And ON (R¹⁴Consisting of
A group selected from the group: (CH (R¹⁴)_c-W¹-(CH (R^Fifteen))_d,here
Wherein c and d are each independently an integer selected from 1-4,¹Is O, S, C
(O), C (S), C (O) O, C (S) O, C (O) S, C (S) S, C (O
) N (R¹⁴), (R¹⁴) NC (O), C (S) N (R¹⁴), (R¹⁴) N
C (S), OC (O) N (R¹⁴), (R¹⁴) NC (O) O, SC (S) N (
R¹⁴), (R¹⁴) NC (S) S, SC (O) N (R¹⁴), (R¹⁴) NC
(O) S, OC (S) N (R¹⁴), (R¹⁴) NC (S) O, N (R^Fifteen) C
(O) N (R¹⁴), (R¹⁴) NC (O) N (R^Fifteen), N (R^Fifteen) C (S
) N (R¹⁴), (R¹⁴) NC (S) N (R^Fifteen), S (O), S (O)₂,
S (O)₂N (R¹⁴), N (R¹⁴) S (O)₂, P (O) (R⁸), N (R ⁷ ) P (O) (R⁸), P (O) (R⁸) N (R⁷), N (R¹⁴), And O
N (R¹⁴And a group selected from the group consisting of (CH (R¹⁴))_e-W^{2 2} -(CH (R^Fifteen))_hA group selected from the group consisting of: wherein e and h are
An integer independently selected from 0 to 2, and W²²Is CR⁴¹= CR⁴² , CR⁴¹R⁴²= C; vinylidene), ethinylidene (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-piper
Dinyl, 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-pi
Loridinyl, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-
Tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and 3,4-tetra
A group selected from the group consisting of hydrofuranyl, provided that R¹⁴And R^FifteenIs
When directly bonded to N, a group selected from a group other than halo and cyano, and (
CR³⁷R³⁸)_b, (CH (R¹⁴))_cAnd (CH (R¹⁴))_eIs E ⁰ Binds to

[0058] Y⁰Is optionally Q^b−Q^ss, Where Q^ssIs (CR³⁷R³⁸) _f , Where f is an integer selected from 1 to 6, (CH (R¹⁴)_c-W¹− (
CH (R^Fifteen))_dWhere c and d are independently selected from 1-4
Integer, W¹Are O, S, C (O), C (S), C (O) O, C (S) O, C (O
) S, C (S) S, C (O) N (R¹⁴), (R¹⁴) NC (O), C (S) N
(R¹⁴), (R¹⁴) NC (S), OC (O) N (R¹⁴), (R¹⁴) NC
(O) O, SC (S) N (R¹⁴), (R¹⁴) NC (S) S, SC (O) N (
R¹⁴), (R¹⁴) NC (O) S, OC (S) N (R¹⁴), (R¹⁴) NC
(S) O, N (R^Fifteen) C (O) N (R¹⁴), (R¹⁴) NC (O) N (R^{1 5} ), N (R^Fifteen) C (S) N (R¹⁴), (R¹⁴) NC (S) N (R^Fifteen)
, S (O), S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴) S (O)₂,
P (O) (R⁸), N (R⁷) P (O) (R⁸), P (O) (R⁸) N (R⁷)
, N (R¹⁴), And ON (R¹⁴A group selected from the group consisting of
CH (R¹⁴))_e-W²-(CH (R^Fifteen))_hA group selected from the group consisting of
Wherein e and h are independently an integer selected from 0 to 2, and W²Is
, CR^4a= CR^4b, Ethinylidene (C≡C; 1,2-ethynyl), and C
= CR^4aR^4bA group selected from the group consisting of:¹⁴And R^FifteenIs
, When directly bonded to N, a group selected from groups other than halo and cyano, and
(CR³⁷R³⁸)_f, (CH (R^Fifteen))_cAnd (CH (R^Fifteen))_eIs
E⁰Binds to

Y ⁰ is, if desired, Q ^b -Q ^sss , where Q ^sss is (CH (R ³⁸ )) _r -W ³ , r is an integer selected from 1 to ³ , and W ³ is 1,1,1-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-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
-On-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,
Selected from the group consisting of 3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl and 3,5-tetrahydropyranyl And the carbon and hydride-containing nitrogens of the ring of W ³ other than each carbon and bond site are optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ^12. With the proviso that (CH (R ³⁸ )) _r is attached to E ⁰ and Q ^b is attached to the lowest substituent of each W ³ ;

[0060] Y⁰Is optionally Q^b−Q^sssr, Where Q^sssrIs (CH (R ³⁸ ))_r-W⁴, R is an integer selected from 1 to 3, W⁴Is 1,2-cyclo
Butyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl
Sil, 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-piperazi
Nil, 1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,
6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl
Lysinyl, 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, 2,
H-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-te
Trahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuran
2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-
Tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetrahydropyran
A group selected from the group consisting of lanyl and 3,5-tetrahydropyranyl, and
And W other than the binding site⁴The ring carbon and the hydride-containing nitrogen of⁹ , R¹⁰, R¹¹And R¹²Replaced by one or more of the group consisting of:
Provided that (CH (R³⁸))_rIs E⁰And Q^bIs each W ⁴ Binds to the highest substituent of

[0061] Y⁰Is optionally Q^b−Q^ssss, Where Q^ssssIs (CH (R ³⁸ ))_r-W⁵, R is an integer selected from 1 to 3, W⁵Is 1,4-ind
Nyl, 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-i
Ndenyl, 2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzo
Furanyl, 2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzo
Furanyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzo
Thiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2
, 7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothio
Phenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,7
-Imidazo (1,2-a) pyridinyl, 3,4-imidazo (1,2-a) pyridinyl
Nil, 3,5-imidazo (1,2-a) pyridinyl, 3,6-imidazo (1,2
-A) pyridinyl, 3,7-imidazo (1,2-a) pyridinyl, 2,4-in
Drill, 2,5-in drill, 2,6-in drill, 2,7-in drill, 3,
4-in drill, 3,5-in drill, 3,6-in drill, 3,7-in drill
1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolin
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolin
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-benz
Isoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazoly
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-quinoyl
Linyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,
4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolini
3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-
Quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquino
Linyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquino
Linyl, 3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquino
Linyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquino
Linyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquino
Linyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl
3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl, 4,
Consists of 6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl
A group selected from the group and W⁵The ring carbon and hydride-containing nitrogen of
By R⁹, R¹⁰, R¹¹And R¹²One or more of the group consisting of
May be substituted, provided that Q^bIs each W⁵Has the least number of substituents
Position (CH (R³⁸))_rIs E⁰Binds to

Y ⁰ is, if desired, Q ^b −Q ^sssr , where Q ^ssssr is (CH
_{^{(R 38)) r -W 6}} , r is an integer selected from 1 to 3, ^{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-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, , 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-
In drill, 2,5-in drill, 2,6-in drill, 2,7-in drill,
3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2, 5-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-benziso Xazolyl, 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-cinnolinyl,
The group selected from the group consisting of 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl, and the carbon and hydride containing nitrogen of the ring of W ⁶ are
May be 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 attached to E ⁰ ;
It is.

Specific examples of the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof are as follows: B is a compound represented by the formula (V):

[0064]

Embedded image (V)

[Wherein D¹, D², J¹, J²And K¹Independently represent C, N, O, S and
And a group selected from the group consisting of:
There is no, D¹, D², J¹, J²And K¹More than one is O
Never, D¹, D², J¹, J²And K¹S is more than one of
Never, D¹, D², J¹, J²And K¹Is O and S, then D ¹ , D², J¹, J²And K¹One must be a covalent bond, and
D¹, D², J¹, J²And K¹More than four cannot be N
But R³², R³³, R³⁴, R³⁵And R³⁶Are each independently a carbon
Maintain tetravalent properties, nitrogen trivalent properties, sulfur divalent properties, and oxygen divalent properties.
R is selected to have; R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁶, R¹⁷, R¹⁸, R¹⁹,
R³², R³³, R³⁴, R³⁵And R³⁶Are independently hydride, aceto
Amide, haloacetamide, amidino, guanidino, dialkylsulfonium,
Trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, f
Teloaralkylthio, heteroaralkoxy, cycloalkylamino, acylal
Kill, acylalkoxy, aryloylalkoxy, heterocyclyloxy, ara
Alkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl,
Perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl,
Aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl
, Halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfur
Finylalkyl, cycloalkylsulfonyl, cycloalkylsulfonyl
Kill, heteroarylamino, N-heteroarylamino-N-alkylamino,
Heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, al
Coxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy
, Cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl,
Chloroalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylene
Dioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocyclo
Alkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino
, Alkoxyamino, thio, nitro, lower alkylamino, alkylthio, al
Quilthioalkyl, arylamino, aralkylamino, arylthio, aryl
Luthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkyl
Rusulfinylalkyl, arylsulfinylalkyl, arylsulfonyl
Alkyl, heteroarylsulfinylalkyl, heteroarylsulfonylua
Alkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfur
Finylalkyl, haloalkylsulfonylalkyl, alkylsulfonamide
, Alkylaminosulfonyl, amidosulfonyl, monoalkylamidosulfonyl
, Dialkylamidosulfonyl, monoarylamidosulfonyl, aryls
Rufonamide, diarylamidosulfonyl, monoalkylmonoarylamide
Sulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio
, Heteroarylsulfinyl, heteroarylsulfonyl, heterocyclyls
Ruphonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, hete
Loaroyl, aralcanoyl, heteroaralkanoyl, haloalkanoyl, al
Kill, alkenyl, alkynyl, alkenyloxy, alkenyloxyalkyl
, Alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloal
Kilalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cyclo
Loalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy
, Hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, al
Kyenylamino, hydroxyheteroaralkyl, haloalkoxyalkyl, ant
Aralkyl, aryloxy, aralkoxy, aryloxyalkyl,
Saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryl
Ruoxy, heteroaryloxyalkyl, arylalkyl, heteroaryl
Alkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl
, Carboalkoxy, alkoxycarboxamide, alkylamide carbonyl
Luamido, arylamidocarbonylamido, carboalkoxyalkyl, cal
Alkoxyalkenyl, carboxy, carboalkoxy, carboxamide
, Carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phos
Honoalkyl, dialalkoxyphosphono and dialalkoxyphosphonoalkyl
A group selected from the group consisting of:

R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵And R³⁶Is optional
And independently Q^bWhere R¹⁶And R¹⁹More than one at the same time,
Q^bIs not, Q^bIs Q^beB is hydride, trialkylsilyl, C2-C8 alkyl, C
3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, C2-
A group selected from the group consisting of C8 haloalkyl and C3-C8 haloalkenyl
Wherein each member of B is optionally up to 6 atoms from the site of attachment of B to A
Any of the carbon atoms including³², R³³, R³⁴, R³⁵And R³⁶Or
B may be optionally substituted with C3-C12 cycloalkyl, C5-C10 cycloalkene.
A group selected from the group consisting of nyl and C4-C9 saturated heterocyclyl, wherein
And each ring carbon is optionally R³³May be substituted by
Any ring carbon other than the ring carbon at the bond site is optionally substituted with oxo.
Provided that more than one ring carbon is simultaneously substituted with oxo
No ring carbon and nitrogen adjacent to the carbon atom at the point of attachment⁹You
And R¹³May be substituted with⁹Adjacent to the site and 2 atoms away from the binding site
The ring carbon or nitrogen atom is optionally R¹⁰May be substituted with ¹³ A ring carbon or nitrogen atom adjacent to the position and two atoms away from the bond is optionally
R¹²May be substituted with R 3 atoms away from the binding site¹⁰Next to rank
The ring carbon or nitrogen atom is optionally¹¹May be replaced by
R 3 atoms away from the merging site¹²A ring carbon or nitrogen atom adjacent to
R³³May be substituted at a position 4 atoms away from the binding site,¹¹and
R³³Is optionally substituted with a ring carbon or nitrogen atom³⁴Has been replaced by
May be;

A is a single covalent bond as well as (W⁷)_rr-(CH (R^Fifteen))_paAnd (C
H (R^Fifteen))_pa− (W⁷)_rrA group selected from the group consisting of
Is an integer selected from 0 to 1, pa is an integer selected from 0 to 6, and W ⁷ Are O, S, C (O), C (O) N (R⁷), C (S) N (R⁷), (R⁷)
NC (O), (R⁷) NC (S) and N (R⁷A group selected from the group consisting of
Where more than one of the group consisting of rr and pa is simultaneously zero.
No; R⁷And R⁸Is independently hydride, hydroxy, alkyl and alcohol
A group selected from the group consisting of xyalkyl; R¹⁴, R^Fifteen, R³⁷And R³⁸Is independently hydride, hydroxy,
Halo, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy and ha
A group selected from the group consisting of lower alkoxyalkyl; R¹⁴And R³⁸Consists of, independently, aroyl, and heteroaroyl
A group selected from the group;⁵, C (O) and S (O)₂A group selected from the group consisting of: R⁵Is selected from the group consisting of hydride, hydroxy, alkyl and alkoxy.
Selected group; R³⁹And R⁴⁰Is independently hydride, hydroxy, halo, hydroxy
Alkyl, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy and
And M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, alkyl, alkenyl, cyano, halo, haloalkyl, ha
Lower alkoxy, haloalkylthio, amino, aminoalkyl, alkylamino,
Amidino, guanidino, hydroxy, hydroxyamino, alkoxy, hydroxy
Consisting of silalkyl, alkoxyamino, thiol, alkylthio and phosphono
A group selected from the group consisting of

R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, (CR⁴¹R⁴²)_q, Where q is selected from 1-3
Integer, (CH (R⁴¹))_g-W⁰-(CH (R⁴²))_p, Where g
And p are independently an integer selected from 0 to 3, W⁰Is O, S, C (O)
, S (O), S (O)₂, N (R⁴¹) And ON (R⁴¹)
Groups selected, and (CH (R⁴¹)_e-W²²-(CH (R⁴²))_hChoose from
Selected groups, wherein e and h are independently an integer selected from 0-2, W ²² Is CR⁴¹= CR⁴², 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-pipera
Dinyl, 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-pi
Loridinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2,3-tetrahi
Drofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl
And a group selected from the group consisting of 3,4-tetrahydrofuranyl, wherein Z ⁰ Is directly attached to the pyrimidinone ring; R⁴¹And R⁴²Is independently amidino, hydroxyamino, hydride,
Hydroxy, amino and alkyl; Q is hydride, but Z⁰Is a single feed bond, formula (II):

[0069]

Embedded image (II)

[Wherein D¹, D², J¹, J²And K¹Independently represent C, N, O, S and
And a group selected from the group consisting of:
There is no, D¹, D², J¹, J²And K¹More than one is O
Never, D¹, D², J¹, J²And K¹S is more than one of
Never, D¹, D², J¹, J²And K¹Is O and S, then D ¹ , D², J¹, J²And K¹One must be a covalent bond, and
D¹, D², J¹, J²And K¹More than four cannot be N
But R³², R³³, R³⁴, R³⁵And R³⁶Are each independently a carbon
Maintain tetravalent properties, nitrogen trivalent properties, sulfur divalent properties, and oxygen divalent properties.
K is selected from (CR^4aR^4b)_nWherein n is an integer selected from 1-2; R^4aAnd R^4bIs independently halo, hydride, hydroxyalkyl, a
Alkyl, alkoxyalkyl, alkylthioalkyl and haloalkyl
A group selected from the group consisting of⁰Is a single covalent bond, C (O), C (S), C (O) N (R⁷), (R⁷) N
C (O), S (O)₂, (R⁷) NS (O)₂And S (O)₂N (R⁷From)
A group selected from the group consisting of: Y⁰Is represented by the formula (IV):

[0071]

Embedded image (IV)

[Wherein D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from a bond, provided that no more than one is a covalent bond,
K²Independently represent C and N⁺A group selected from the group consisting of⁵, D⁶, J ⁵ And J⁶Is not O, and D⁵, D⁶, J⁵and
J⁶Is not S, and D⁵, D⁶, J⁵And J⁶2
If one is O and S, D⁵, D⁶, J⁵And J⁶One must be a covalent bond
Must and K²Is N⁺In the case of D⁵, D⁶, J⁵And J⁶More than three
But not N, and K²If is carbon, D⁵, D⁶, J⁵and
J⁶Cannot be N, provided that R¹⁶, R¹⁷, R¹⁸ And R¹⁹Are independently, each independently, the tetravalent nature of carbon, the trivalent nature of nitrogen
, The divalent nature of sulfur and the divalent nature of oxygen
A group represented by]; Q^bIs NR²⁰R²¹,⁺NR²⁰R²¹R²², Aminoalkylenyl and
And Q^beA group selected from the group consisting of^beIs a hydride and R^{2 0} , R²¹And R²²Is independently hydride, alkyl, hydroxy,
, Aminoalkylenyl, dialkylamino, alkylamino and hydroxy
A group selected from the group consisting of alkyl, provided that R²⁰, R²¹And R²²of
More than one, at the same time, hydroxy, amino, alkylamino or dialkyi
Never be Lamino; Q^bIs optionally C (NR²⁵) NR²³R²⁴, N (R²⁶) C (NR ²⁵ ) N (R²³) (R²⁴), C (O) N (R²⁶) C (NR²⁵) N (R^{2 3} ) (R²⁴), N (R²⁶) N (R²⁶) C (NR²⁵) N (R²³) (R^{2 4} ) And ON (R²⁶) C (NR²⁵) N (R²³) (R²⁴A group consisting of
A group selected from:²³, R²⁴And R²⁶Any of the group consisting of
When two are bonded to the same atom, R²³, R²⁴And R²⁶More than one of
, Hydroxy, alkylamino, amino, or dialkylamino
No; R²³, R²⁴, R²⁵And R²⁶Is independently hydride, alkyl,
Droxy, amino, alkylenylamino, dialkylamino, alkylamino,
And a group selected from the group consisting of: hydroxyalkyl;

Q^sIs a single covalent bond and (CR³⁷R³⁸)_b− (W⁰)_az, Here a
z is an integer selected from 0 to 1, b is an integer selected from 1 to 5, W⁰Is
O, C (O), S (O), S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴)
S (O)₂And N (R¹⁴), A group selected from the group consisting of (CH (R¹⁴)
)_c-W¹-(CH (R^Fifteen))_dWherein c and d are independently 1 to 4
An integer selected from W¹Are O, S, C (O), C (S), C (O) O, C (
S) O, C (O) S, C (S) S, C (O) N (R¹⁴), (R¹⁴) NC (O
), C (S) N (R¹⁴), (R¹⁴) NC (S), OC (O) N (R¹⁴),
(R¹⁴) NC (O) O, SC (S) N (R¹⁴), (R¹⁴) NC (S) S,
SC (O) N (R¹⁴), (R¹⁴) NC (O) S, OC (S) N (R¹⁴),
(R¹⁴) NC (S) O, N (R^Fifteen) C (O) N (R¹⁴), (R¹⁴) NC
(O) N (R^Fifteen), N (R^Fifteen) C (S) N (R¹⁴), (R¹⁴) NC (S
) N (R^Fifteen), S (O), S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴ ) S (O)₂, P (O) (R⁸), N (R⁷) P (O) (R⁸), P (O) (R ⁸ ) N (R⁷), N (R¹⁴) And ON (R¹⁴Selected from the group consisting of
Group, and (CH (R¹⁴))_e-W²²-(CH (R^Fifteen))_hGroup consisting of
Wherein e and h are independently an integer selected from 0 to 2
, And W²²Is CR⁴¹= CR⁴², CR⁴¹R⁴²= 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-
Rufolinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl
Nil, 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
Lysinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetra
Selected from the group consisting of hydrofuranyl, and 3,4-tetrahydrofuranyl
Group, provided that R¹⁴And R^FifteenIs halo and shea when directly bonded to N
A group selected from groups other than³⁷R³⁸)_b, (CH (R¹⁴)
)_cAnd (CH (R¹⁴))_eIs E⁰Binds to

[0074] Y⁰Is optionally Q^b−Q^ss, Where Q^ssIs (CR³⁷R³⁸) _f Where f is an integer selected from 1 to 4, (CH (R¹⁴))_c-W¹−
(CH (R^Fifteen))_dWhere c and d are independently selected from 1-2.
Integer, W¹Are O, S, C (O), C (O) N (R¹⁴), (R¹⁴) NC (
O), N (R^Fifteen) C (O) N (R¹⁴), (R¹⁴) NC (O) N (R^Fifteen)
, N (R¹⁴) And ON (R¹⁴A group selected from the group consisting of:
H (R¹⁴))_e-W²-(CH (R^Fifteen))_hA group selected from the group consisting of
Here, e and h are independently an integer selected from 0 to 2, and W²Is
CR^4a= CR^4b, Ethinylidene (C≡C; 1,2-ethynyl), and C =
CR^4aR^4bA group selected from the group consisting of:¹⁴And R^FifteenIs
When directly bonded to N, a group selected from a group other than halo, and (CR³⁷R^{3 8} )_f, (CH (R^Fifteen))_cAnd (CH (R^Fifteen))_eIs E⁰Join to
; Y⁰Is optionally Q^b−Q^sssWhere Q^sssIs (
CH (R³⁸))_r-W³, R is an integer selected from 1 to 2, W³Is 1,1
-Cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclopropyl
Clobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclo
Hexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholy
Nil, 2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,
4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-pipe
Radinyl, 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
Nyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,
6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrol
Lysinyl, 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, 2
H-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-tetrahydro
Furanyl, 2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,
5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetrahydride
A group selected from the group consisting of lopyranyl and 3,5-tetrahydropyranyl,
And the carbon and hydride-containing nitrogens of the ring of W3 other than the binding site are optionally
R⁹, R¹⁰, R¹¹And R¹²Replaced by one or more of the group consisting of
Provided that (CH (R³⁸))_rIs E⁰And Q^bAre each
W³Binds to the position with the least number of substituents;

Y ⁰ can be Q ^b -Q ^sssr if desired, where Q ^sssr is (CH (R ³⁸ )) _r -W ⁴ , where r is an integer selected from 1-2 , 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, 2,4-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 The group selected from the group consisting of pyranyl, 3,4-tetrahydropyranyl and 3,5-tetrahydropyranyl, and the carbon and hydride-containing nitrogens of the ring of W ⁴ other than the bonding site are optionally R ⁹ , It may be substituted with one or more of the group consisting of R ¹⁰ , R ¹¹ and R ¹² , provided that (CH (R ³⁸ )) _r is attached to E ⁰ and Q ^b is each W ⁴ is attached to the position having the largest number of substituents;

Y ⁰ may be Q ^b -Q ^ssss , where desired, where Q ^ssss is (CH (R ³⁸ )) _r -W ⁵ , where r is an integer selected from 1-2 , 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,
, 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-isoindolyl, 2,5-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-benziso Xazolyl, 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-
A group selected from the group consisting of cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl, and W ⁵ The ring carbon and hydride-containing nitrogen may be optionally substituted with one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , wherein Q ^b is each W ⁵ is attached to the position having the least number of substituents, and (CH (R ³⁸ )) _r is attached to E ⁰ ;

[0077] Y ⁰ is optionally ^may be a Q ^{b -Q SSSSR,, here, Q ssss r _{is, (CH (R 38))}} r -W 6, r is selected from 1-2 An integer, W ⁶ is 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl,
, 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-
In drill, 3,4-in drill, 3,5-in drill, 3,6-in drill,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,
6-isoindolyl, 2,4-isoindolyl, 2,5-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-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,
A group selected from the group consisting of 6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl and 4,8-cinnolinyl, and The ring carbon and hydride-containing nitrogen of W ⁶ may be optionally substituted by one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , wherein Q ^b is each the binding to highest position in the number of substituents ^{W 6, (CH (R 38} )) r, binds to ^{E 0;} a.

Specific examples of the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof are as follows: J is represented by O;

[0079]

Embedded image

[Wherein, R⁹, R¹⁰, R¹¹, R¹², R¹³, R³², R³³, R³⁴, R ³⁵ And R³⁶Is independently hydride, acetamido, haloacetamide,
Amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyl
Oxy, alkoxy, alkoxyalkyl, haloalkoxyalkyl, hydroxy
, Amino, alkoxyamino, nitro, lower alkylamino, alkylthio,
Alkylthioalkyl, alkylsulfinyl, alkylsulfonyl, alkyl
Sulfonylalkyl, aryl, aralkyl, cycloalkyl, cycloalkyl
Alkyl, alkylsulfonamide, alkylaminosulfonyl, amidosulfo
Nil, monoalkylamidosulfonyl, dialkylamidosulfonyl, alkano
Yl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloa
Lucenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, a
Minoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy
C, carboxy, carboxamide, carboxamidoalkyl and cyano
A group selected from the group consisting of:⁹, R¹⁰, R¹¹, R¹²And R¹³Is optionally a heteroaryl
And a group selected from the group consisting of:⁹, R¹⁰, R ¹¹ , R¹²And R¹³Is a substituent for a group other than B; R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵And R³⁶Is optional
And independently Q^bWhere R¹⁶And R¹⁹More than one at the same time,
Q^bIs not, Q^bIs Q^be B is hydride, trialkylsilyl, C2-C8 alkyl, C
3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl and C
A group selected from the group consisting of 2-C8 haloalkyl, wherein each member of group B is
Optionally, any carbon comprising up to 6 atoms from the attachment site of B to A is
R³², R³³, R³⁴, R³⁵And R³⁶One or more of the group consisting of
And may be substituted;

[0081] B is a group selected from the group consisting of C3-C12 cycloalkyl and C4- heterocyclyl, wherein each ring carbon is optionally ^may be substituted with ^{R 33,} binding of B to A Any ring carbon other than the ring carbon of the site may be optionally substituted by oxo, provided that no more than one ring carbon is simultaneously replaced by oxo. The ring carbon and nitrogen adjacent to the atom may be optionally substituted with R ⁹ and R ¹³ , and adjacent to R ⁹ ,
A ring carbon or nitrogen atom 2 atoms away from the bonding site may be optionally substituted with R ¹⁰ and a ring carbon or nitrogen atom adjacent to the R ¹³ position and 2 atoms away from the bonding site may optionally be The ring carbon or nitrogen atom adjacent to the R ¹⁰ position which may be substituted by R ¹² and is 3 atoms away from the bonding site may be optionally substituted by R ¹¹ and is 3 atoms away from the bonding site The ring carbon or nitrogen atom adjacent to R ¹² may be optionally substituted with R ³³ , and 4
A ring carbon or nitrogen atom adjacent to R ¹¹ and R ³³ which is separated by an atom may be optionally substituted by R ³⁴ ; A is a single covalent bond and (W ⁷ ) _rr — (CH (R ¹⁵ )) _Pa and (C
_{^{H (R 15)) pa -}} (W 7) a group selected from the group consisting of _rr, here, rr
Is an integer selected from 0 to 1, pa is an integer selected from 0 to 6, and
W ⁷ is O, S, C (O), (R ⁷ ) NC (O), (R ⁷ ) NC (S) and N
No more than one group selected from the group consisting of (R ⁷ ), wherein rr and pa are simultaneously 0; R ⁷ is selected from the group consisting of hydride, hydroxy and alkyl R ¹⁵ is a group selected from the group consisting of hydride, hydroxy, halo, alkyl and haloalkyl; Ψ is a group selected from the group consisting of NH and NOH;

M is a group selected from the group consisting of N and R ¹ -C; R ¹ is hydride, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio, amino, aminoalkyl, alkylamino ,
Amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl,
A group selected from the group consisting of alkoxyamino, thiol and alkylthio; R ² is a group represented by Z ⁰ -Q; Z ⁰ is a single covalent bond and (CR ⁴¹ R ⁴² ) _q , wherein q is An integer selected from 1 to 3, (CH (R ⁴¹ )) _g -W ^0- (CH (R ⁴² )) _p , wherein g and p are an integer selected from 0 to 3, and W ⁰ is O, S, C (
From _{^{(CH (R 42)) h}} - O), S (O), N (R 41) and ON ^(group selected from the group consisting of ^{R 41) _{and, (CH (R 41))}} e -W 22 A group selected from the group consisting of: wherein e and h are independently an integer selected from 0 to 1, W ²² is CR ⁴¹ ＣＲCR 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
A group selected from the group consisting of -pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydrofuranyl With the proviso that Z ⁰ is directly attached to the pyrimidinone ring; R ⁴¹ and R ⁴² are independently amidino, hydroxyamino, hydride,
A group selected from the group consisting of hydroxy, amino and alkyl; Q is a hydride, wherein Z ⁰ is a group other than a single covalent bond, and formula (II):

[0083]

Embedded image (II)

[Wherein D¹, D², J¹, J²And K¹Independently represent C, N, O, S and
And a group selected from the group consisting of:
There is no, D¹, D², J¹, J²And K¹More than one is O
Never, D¹, D², J¹, J²And K¹S is more than one of
Never, D¹, D², J¹, J²And K¹Is O and S, then D ¹ , D², J¹, J²And K¹One must be a covalent bond, and
D¹, D², J¹, J²And K¹More than four cannot be N
But R³², R³³, R³⁴, R³⁵And R³⁶Are each independently a carbon
Maintain tetravalent properties, nitrogen trivalent properties, sulfur divalent properties, and oxygen divalent properties.
K is a group selected from the group consisting of:^4aR^4b)_nWherein n is an integer selected from 1-2; R^4aAnd R^4bIs independently halo, hydride, hydroxyalkyl, a
From alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl
A group selected from the group consisting of: E⁰Is that K is (CR^4aR^4b)_nThen E¹, Where E¹Is a simple shared connection
C (O), C (S), C (O) N (R⁷), (R⁷) NC (O), S (O) ₂ , (R⁷) NS (O)₂, And S (O)₂N (R⁷Selected from the group consisting of
Group; Y⁰Is represented by the formula (IV):

[0085]

Embedded image (IV)

[Wherein D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from a bond, provided that more than one is not a covalent bond but a K²Is C
, D⁵, D⁶, J⁵And J⁶Is not O, and D⁵,
D⁶, J⁵And J⁶Is not S, and D⁵, D⁶, J ⁵ And J⁶Is O and S, then D⁵, D⁶, J⁵And J⁶One of the
Must be a covalent bond, D⁵, D⁶, J⁵And J⁶More than four are N
Where R¹⁶, R¹⁷, R¹⁸And R¹⁹Are independent
To obtain carbon tetravalent, nitrogen trivalent, sulfur divalent and oxygen
Selected to maintain the nature of valency]; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Nitro, alkoxyamino, lower alkylamino, alkylthio, alkylsul
Finyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl,
Alkenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, al
Consists of killamino, haloalkoxyalkyl, carboalkoxy and cyano
A group selected from the group; Q^bIs NR²⁰R²¹, Aminoalkylenyl, Q^be, Where Q^beIs
Hydride and N (R²⁶) C (NR²⁵) N (R²³) (R²⁴),and
C (NR²⁵) NR²³R²⁴A group selected from the group consisting of:²⁰You
And R²¹More than one, at the same time, hydroxy, amino, alkylamino or
Or dialkylamino, and R²³And R²⁴One of
Often, at the same time, hydroxy, amino, alkylamino or dialkylamido
It cannot be R; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
De, alkyl, hydroxy, aminoalkylenyl, amino, dialkylamino,
A group selected from the group consisting of alkylamino and hydroxyalkyl; Q^sIs a single covalent bond, (R³⁷R³⁸)_b, Where b is selected from 1-4
Integer, and (CH (R¹⁴))_c-W¹-(CH (R^Fifteen))_dConsisting of
A group selected from the group wherein c and d are independently selected from 1-3
Integer, and W¹Is C (O) N (R¹⁴), (R¹⁴) NC (O), S (O)
, S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴) S (O)₂And N (R ¹⁴ A group selected from the group consisting of:¹⁴Is directly bonded to N
, A group selected from groups other than halo, and (CR³⁷R³⁸)_bAnd (CH
(R¹⁴))_cIs E⁰Binds to

R ¹⁴ is a group selected from the group consisting of hydride, halo, alkyl and haloalkyl; R ³⁷ and R ³⁸ are independently a group selected from the group consisting of hydride, alkyl and haloalkyl; R ³⁸ Is optionally a group selected from the group consisting of aroyl and heteroaroyl; Y ⁰ is optionally a group represented by Q ^b -Q ^ss , wherein Q ^ss is (CH
(R ¹⁴ )) _e -W ^2- (CH (R ¹⁵ )) _h , where e and h are independently an integer selected from 1-2, and W ² is CR ^4a = CR ^4b Wherein (CH (R ¹⁴ )) _e is bonded to E ⁰ ;

Y ⁰ is optionally a group selected from the group consisting of Q ^b -Q ^ssss and Q ^b -Q ^ssssr , wherein Q ^sss 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, and, ^{W 5} and ^{W 6} being independently 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-isoindolyl, 2,5-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
-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 2,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl,
4,7 cinnolinyl and 4,8-cinnolinyl group selected from the group consisting of and,, ^{W 5} and non-binding sites of ^{W 6,} ring carbon and hydride-containing ring nitrogen and ^{W 6} of ^{W 5} is If desired, one or more of the group consisting of R ⁹ , R ¹⁰ , R ¹¹ and R ¹² may be substituted, provided that Q ^b is the position with the least number of substituents on each W ⁵ And Q ^b is bonded to the position with the highest number of substituents on each W ⁶ , and (CH (R ³⁸ )) _r is bonded to E ⁰ .

More specific examples of the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof, wherein J is O;

[0090]

Embedded image

[Wherein, R³², R³³, R³⁴, R³⁵And R³⁶, Independently, hydride
, Acetamide, haloacetamide, amidino, guanidino, alkylenedioxy
Si, haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino
, Alkoxyamino, alkanoyl, haloalkanoyl, nitro, lower alkyl
Amino, alkylthio, aryl, aralkyl, cycloalkyl, cycloalkyl
Alkyl, alkylsulfonamide, amidosulfonyl, monoalkylamide
Sulfonyl, dialkylamidosulfonyl, alkyl, alkenyl, halo, halo
Alkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, alkyleni
Ruamino, carboalkoxy, carboxy, carboxamide, cyano and Q ^b B is a hydride, a trialkylsilyl, a C2-C8 alkyl, a C2
3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl and C
A group selected from the group consisting of 2-C8 haloalkyl, wherein each member of group B is
Optionally, any carbon containing up to 6 atoms from the site of attachment of B to A is
R³², R³³, R³⁴, R³⁵And R³⁶One or more of the group consisting of
And B is a group consisting of C3-C12 cycloalkyl and C4-heterocyclyl.
Groups selected from wherein each ring carbon is optionally R³³Even if
Frequently, any ring carbon other than the ring carbon of the bonding site of B to A can be optionally
, Oxo, provided that at the same time more than one ring carbon is
Ring carbons and nitrogens adjacent to the carbon atom at the point of attachment that are not substituted for xo
Is optionally R⁹And R¹³May be substituted with⁹Adjacent to the site
, A ring carbon or nitrogen atom two atoms away from the bond is optionally¹⁰Put in
May be replaced by R¹³Ring carbon adjacent to the site and two atoms away from the binding site
Or a nitrogen atom, if desired,¹²May be substituted from the binding site
Atom away, R¹⁰The ring carbon or nitrogen atom adjacent to the position¹¹ May be substituted with 3 atoms away from the binding site,¹²Ring carbon adjacent to
Or a nitrogen atom, if desired,³³May be substituted from the binding site
4 atoms away, R¹¹And R³³A ring carbon or nitrogen atom adjacent to
Than R³⁴May be substituted;

R⁹, R¹⁰, R¹¹, R¹²And R¹³Are independently hydride, aceto
Amide, haloacetamide, alkoxyamino, alkanoyl, haloalkanoy
, Amidino, guadinino, alkylenedioxy, haloalkylthio, alkoxy
Si, hydroxy, amino, lower alkylamino, alkylthio, alkylsulf
Ynyl, alkylsulfonyl, alkylsulfonamide, amidosulfonyl,
Noalkylamidosulfonyl, dialkylamidosulfonyl, alkyl, halo,
Haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, cal
Selected from the group consisting of boxyalkyl, carboxy, carboxamide, and cyano
Selected group; R⁹, R¹⁰, R¹¹, R¹²And R¹³Is optionally a heteroaryl
And a group selected from the group consisting of:⁹, R¹⁰, R ¹¹ , R¹²And R¹³Is a substituent for a group other than B; A is a single covalent bond and ((CH (R^Fifteen))_pa− (W⁷)_rrGroup consisting of
Wherein rr is an integer selected from 0 to 1 and pa is 0 to
An integer selected from 3 and W⁷Are O, S, C (O), (R⁷) NC (O)
, (R⁷) NC (S) and N (R⁷R) a group selected from the group consisting of:⁷Is a group selected from the group consisting of hydride, hydroxy and alkyl;^FifteenIs composed of hydride, hydroxy, halo, alkyl and haloalkyl.
A group selected from the group consisting of

Ψ is NH; M is a group selected from the group consisting of N and R ¹ -C; R ¹ is hydride, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl , alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, groups selected from the group consisting of alkoxy, amino, thiol and alkylthio; R ² is a group represented by Z ^{0 -Q;} Z 0 is a single covalent A bond as well as (CR ⁴¹ R ⁴² ) _q , where q is an integer selected from 1-2, (CH (R ⁴¹ )) _g -W ^0- (CH (R ⁴² )) _p , where g and p is independently an integer selected from 0 to 3, W ⁰ is a group selected from the group consisting of O, S and N (R ⁴¹ ), and (CH (R ⁴¹ )) _{^{e -W 2 2 - (CH (}} R 42)) a group selected from the group consisting of _h, herein, e and h are independently an integer 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 A group selected from the group consisting of, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydrofuranyl, wherein Z ⁰ is directly bonded to the pyrimidinone ring; R ⁴¹ and R ⁴² are A group independently selected from the group consisting of hydride, hydroxy and amino; Q is hydride, wherein Z ⁰ is a group other than a single covalent bond, a group selected from the group consisting of aryl and heteroaryl, In addition, the carbon adjacent to the carbon at the bonding site may be optionally substituted with R ⁹ , The other carbons in contact may optionally be substituted with R ¹³ , the carbon adjacent to R ⁹ and two atoms away from the carbon at the binding site may optionally be substituted with R ¹⁰ , adjacent to R ^13, carbon distant 2 atoms from the carbon of the binding site is optionally, may be substituted in R ^{1 2,} all of the carbon adjacent to the binding site of both R ¹⁰ and R ^12, optionally Accordingly, it may be substituted with R ^11; K is a group represented by CHR ^4a, here, R ^4a is selected hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, from the group consisting of alkylthioalkyl, and haloalkyl A group; E ⁰ is a single covalent bond and C (O) N (H), (H) NC (O), (R ⁷ )
A group selected from the group consisting of NS (O) ₂ and S (O) ₂ N (R ⁷ ); Y ⁰ is a group represented by the formula (IV):

[0094]

Embedded image (IV)

[Wherein D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from a bond, provided that more than one is not a covalent bond but a K²Is C
, D⁵, D⁶, J⁵And J⁶Is not O, and D⁵,
D⁶, J⁵And J⁶Is not S, and D⁵, D⁶, J ⁵ And J⁶Is O and S, then D⁵, D⁶, J⁵And J⁶One of the
Must be a covalent bond, D⁵, D⁶, J⁵And J⁶More than four are N
Where R¹⁶, R¹⁷, R¹⁸And R¹⁹Are independent
To obtain carbon tetravalent, nitrogen trivalent, sulfur divalent and oxygen
Selected to maintain the nature of valency]; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl
, Alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, ha
Loalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and shea
A group selected from the group consisting of¹⁶And R¹⁹Is optionally Q^bWhere R¹⁶And R¹⁹Of 1
More than one, at the same time, Q^bIs not, Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride and N (R ²⁶ ) C (NR²⁵) N (R²³) (R²⁴), And C (NR²⁵) NR²³ R²⁴A group selected from the group consisting of:²⁰And R²¹More than one of
But simultaneously with hydroxy, amino, alkylamino or dialkylamino
There is no, R²³And R²⁴More than one is simultaneously a hydroxy,
Cannot be amino, alkylamino or dialkylamino; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
, Alkyl, hydroxy, amino, alkylamino and dialkylamino
A group selected from the group consisting of:

Q^sIs a single covalent bond and (R³⁷R³⁸)_b, Where b is from 1-4
The selected integer, and (CH (R¹⁴))_c-W¹-(CH (R^Fifteen))_dOr
Wherein c and d are independently an integer selected from 1-3
, And W¹Is C (O) N (R¹⁴), (R¹⁴) NC (O), S (O), S
(O)₂, S (O)₂N (R¹⁴), N (R¹⁴) S (O)₂And N (R¹⁴ A group selected from the group consisting of:¹⁴Is, when directly bonded to N,
Groups selected from groups other than b, and (CR³⁷R³⁸)_bAnd (CH (R ¹⁴ ))_cIs E⁰Binds to R¹⁴Is selected from the group consisting of hydride, halo, alkyl and haloalkyl
Group to be used; R³⁷And R³⁸Is independently hydride, alkyl and haloalkyl
A group selected from the group consisting of: R³⁸Is optionally selected from the group consisting of aroyl and heteroaroyl
Group; Y⁰Is optionally Q^b−Q^ssWherein Q is a group represented by^ssIs (CH
(R¹⁴))_e-W²-(CH (R^Fifteen))_hWhere e and h are independently
And an integer selected from 1-2, and W²Is CR^4a= CH, where (C
H (R¹⁴))_eIs E⁰Binds to

Still more specific examples of the compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein: J is O;

[0098]

Embedded image

Wherein R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently hydride, acetamido, haloacetamide, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino , Alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl,
Alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, groups represented by radical selected from the group consisting of cyano and Q ^b; A is a single covalent bond and (CH (R _{^{15)) pa - (W 7}} ) a group selected from the group consisting of _rr, here, rr is an integer selected from 0 to 1, pa is 0-3
And W ⁷ is a group selected from the group consisting of (R ⁷ ) NC (O) and N (R ⁷ ); R ⁷ is selected from the group consisting of hydride, hydroxy and alkyl A group wherein R ¹⁵ is selected from the group consisting of hydride, halo, alkyl and haloalkyl; Ψ is NH; a group wherein M is selected from the group consisting of N and R ¹ -C; R ¹ is hydride A group selected from the group consisting of, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo;

R²Is Z⁰A group represented by -Q; Z⁰Is O, S, NH and CH²A group selected from the group consisting of: aryl and heteroaryl, wherein Q is selected from the group consisting of aryl and heteroaryl.
One carbon adjacent to the carbon at the binding site may optionally be R⁹Even if
Often, the other carbon adjacent to the carbon at the binding site is optionally R¹³Is replaced by
May be, R⁹Adjacent to and two atoms away from the carbon at the binding site,
R¹⁰May be substituted with¹³, And two atoms from the carbon at the binding site
The detached carbon is optionally R¹²May be substituted with¹⁰And R ¹² All carbons adjacent to both are optionally R¹¹May be replaced by
R⁹, R¹¹And R¹³Is independently hydride, hydroxy, amino, a
Midino, guanidino, lower alkylamino, alkylthio, alkylsulfone
Amide, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoa
Rukylamidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloa
Lucoxy, hydroxyalkyl, carboxy, carboxamide and cyano
A group selected from the group consisting of: R¹⁰And R¹²But independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, al
Coxyamino, lower alkylamino, alkylsulfonamide, amidosulfonyl
, Monoalkylamidosulfonyl, dialkylamidosulfonyl, hydroxya
Alkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl
Selected from the group consisting of amide carbonyl, halo, haloalkyl and cyano
K is CH₂E⁰Is C (O) N (H); Y⁰Is represented by the formula (IV):

[0101]

Embedded image (IV)

[Wherein D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from a bond, provided that more than one is not a covalent bond but a K²Is C
, D⁵, D⁶, J⁵And J⁶Is not O, and D⁵,
D⁶, J⁵And J⁶Is not S, and D⁵, D⁶, J ⁵ And J⁶Is O and S, then D⁵, D⁶, J⁵And J⁶One of the
Must be a covalent bond, D⁵, D⁶, J⁵And J⁶More than four are N
A group represented by the formula: R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl
, Alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloa
Selected from the group consisting of lucoxy, hydroxyalkyl, aminoalkyl and cyano
Selected group; R¹⁶And R¹⁹Is optionally Q^bWhere R¹⁶And R^{1 9} More than one at the same time, Q^bIs not, Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride, and
C (NR²⁵) NR²³R²⁴A group selected from the group consisting of, but simultaneously
R²⁰And R²¹Is not hydroxy, and R²³You
And R²⁴No more than one is hydroxy; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
Q, a group selected from the group consisting of alkyl, and hydroxy;^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
;

Further more specific examples of the compounds of formula (I) or pharmaceutically acceptable salts thereof are: J is O; B is optionally hydride, C2-C8 alkyl, C3-C8 alkenyl ,
A group selected from the group consisting of C3-C8 alkynyl and C2-C8 haloalkyl, wherein each member of B is optionally any carbon up to 6 atoms from the point of attachment of B to A, wherein ^R32 , R ^{33, R 34, R 35} and ^{R 36} may be substituted by one or more radicals of the group consisting of; ^{R 32,} R ^33, R ^{34, R 35} and ^{R 36,} independently, Hydride, acetamide, haloacetamide, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, Carboalkoxy, carboxy, carboxy De, cyano and ^Q groups are selected from the group consisting of ^b; A is a single covalent bond and _{^{(CH (R 15)) pa}} - group selected from the group consisting of (W _{7) rr,} here, rr is , An integer selected from 0 to 1, pa is 0 to 3
And W ⁷ is a group selected from the group consisting of (R ⁷ ) NC (O) and N (R ⁷ ); R ⁷ is selected from the group consisting of hydride, hydroxy and alkyl A group; R ¹⁵ is a group selected from the group consisting of hydride, halo, alkyl and haloalkyl;

Ψ is NH; M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, hydroxy, hydroxyamino, amidino, amino, shea
No, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoal
Kill, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and
A group selected from the group consisting of halo; R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, O, S, NH and CH₂A group selected from the group consisting of
Q is a group selected from the group consisting of aryl and heteroaryl, wherein
One carbon adjacent to the carbon at the binding site may optionally be R⁹Even if
Often, the other carbon adjacent to the carbon at the binding site is optionally R¹³Is replaced by
May be, R⁹Adjacent to and two atoms away from the carbon at the binding site,
R¹⁰May be substituted with¹³, And two atoms from the carbon at the binding site
The detached carbon is optionally R¹²May be substituted with¹⁰And R ¹² All carbons adjacent to both are optionally R¹¹May be replaced by
R⁹, R¹¹And R¹³Is independently hydride, hydroxy, amino, a
Midino, guanidino, lower alkylamino, alkylthio, alkylsulfone
Amide, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoa
Rukylamidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloa
Lucoxy, hydroxyalkyl, carboxy, carboxamide and cyano
A group selected from the group consisting of: R¹⁰And R¹²Is independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, al
Coxyamino, lower alkylamino, alkylsulfonamide, amidosulfoni
Monoalkylamidosulfonyl, dialkylamidosulfonyl, hydroxyal
Kill, alkylenylamino, carboalkoxy, carboxy, carboxyalkyl
Amide, amide carbonyl, halo, haloalkyl and cyano
K is CH²E⁰Is C (O) N (H); Y⁰Is represented by the formula (IV):

[0105]

Embedded image (IV)

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently a group selected from C, N, O, S and a covalent bond, provided that more than one is a covalent bond Is not
K ² is not O, more than one of C, D ⁵ , D ⁶ , J ⁵ and J ⁶ is O, and more than one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S There is nothing, D ⁵ ,
When two of D ⁶ , J ⁵ and J ⁶ are O and S, one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be a covalent bond, and D ⁵ , D ⁶ , J ⁵ and J ^No more than four of ⁶ can be N, provided that R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are
Each independently selected to maintain the tetravalent nature of carbon, the trivalent nature of nitrogen, the divalent nature of sulfur and the divalent nature of oxygen; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ is independently hydride, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
R ¹⁶ and R ¹⁹ are groups selected from the group consisting of lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkylenylamino and cyano; , Optionally Q ^b , provided that one of R ¹⁶ and R ¹⁹
Many than one is, that they are not simultaneously ^{Q b, Q b} is ^Q be; ^{Q b is, NR 20 R 21, Q be} , ^{here, Q BE} is hydrido, C (N
^{R 25) NR} 23 R ²⁴ and ^{N (R 26) C (NR} 25) N (R 23) ( a group selected from the group consisting of ^{R 2 4),} however, at the same ^time, than one of ^{R 20} and ^{R 21} Many are not hydroxy and, at the same time, no more than one of R ²³ and R ²⁴ are hydroxy; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are A group independently selected from the group consisting of hydride, alkyl and hydroxy; Q ^s is a group selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ .

Further details of the compound of formula (I) or a pharmaceutically acceptable salt thereof
Specific examples are: J is O; B is selected from the group consisting of C3-C7 cycloalkyl and C4 heterocyclyl.
A selected group, wherein each ring carbon is optionally R³³May be replaced by
, A ring carbon other than the ring carbon in the bonding site of B to A is optionally substituted with oxo.
Provided that more than one ring carbon is simultaneously substituted with oxo.
And the ring carbon and nitrogen adjacent to the carbon at the point of attachment can optionally be R ⁹ Or R¹³May be substituted with⁹Adjacent to the site, 2 sites from the binding site
An isolated ring carbon or nitrogen is R¹⁰May be substituted with¹³Next to rank
And a ring carbon or nitrogen two atoms away from the binding site is R¹²Even if
Often, three atoms away from the binding site, R¹⁰The ring carbon adjacent to the moiety is R¹¹Put in
R 3 which is 3 atoms away from the binding site¹²Ring carbon adjacent to site
Is R³³May be substituted at a position 4 atoms away from the binding site,¹¹and
R³³The ring carbon adjacent to the position is R³⁴May be substituted; R⁹, R¹¹And R¹³Is independently hydride, hydroxy, amino, a
Midino, guanidino, lower alkylamino, alkylthio, alkylsulfone
Amide, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoa
Rukylamidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloa
Lucoxy, hydroxyalkyl, carboxy, carboxamide and cyano
A group selected from the group consisting of: R¹⁰And R¹²Is independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, al
Coxyamino, lower alkylamino, alkylsulfonamide, amidosulfoni
, Monoalkylamidosulfonyl, dialkylamidosulfonyl, hydroxy
Alkyl, alkylenylamino, carboalkoxy, carboxy, carboxyl
Selected from the group consisting of alkyl, amidocarbonyl, halo, haloalkyl and cyano.
Group selected;

R³³And R³⁴Is independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamido
, Lower alkylamino, alkylthio, amidosulfonyl, monoalkylamido
Dosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl,
Haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carbo
Xyxamide, cyano and Q^bA is a single covalent bond and ((CH (R^Fifteen))_pa− (W⁷)_rrGroup consisting of
Wherein rr is an integer selected from 0 to 1 and pa is 0 to
An integer selected from 3 and W⁷Is (R⁷) NC (O) and N (R⁷) Or
A group selected from the group consisting of: R⁷Is a group selected from the group consisting of hydride, hydroxy and alkyl;^FifteenIs selected from the group consisting of hydride, halo, alkyl and haloalkyl
Ψ is NH; M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, hydroxy, hydroxyamino, amidino, amino, shea
No, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoal
Kill, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and
A group selected from the group consisting of halo; R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, O, S, NH and CH₂A group selected from the group consisting of
Q is a group selected from the group consisting of aryl and heteroaryl, wherein
The carbon adjacent to the carbon at the site of attachment may optionally be R⁹May be replaced by
Other carbons adjacent to the carbon at the binding site may optionally be R¹³Even if
Well, R⁹And two carbons away from the carbon at the site of attachment, if desired, ¹⁰ May be substituted with¹³Adjacent to and 2 atoms away from the carbon at the binding site
Carbon is optionally R¹²May be substituted with¹⁰And R¹²Both
Any adjacent carbon of the other binding site may optionally be R¹¹Has been replaced by
K is CH₂E⁰Is C (O) N (H); Y⁰Has the formula (IV):

[0109]

Embedded image (IV)

[Wherein D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from a bond, provided that no more than one is a covalent bond,
K²Is C and D⁵, D⁶, J⁵And J⁶O is more than one of
But not D⁵, D⁶, J⁵And J⁶No more than one is S
D⁵, D⁶, J⁵And J⁶Is O and S, then D⁵, D⁶, J⁵And
And J⁶One must be a covalent bond and D⁵, D⁶, J⁵And J⁶The four
More cannot be N, except that R¹⁶, R¹⁷, R¹⁸And R^{1 9} Are, independently and independently of each other, carbon tetravalent, nitrogen trivalent, sulfur
Selected to maintain the divalent nature of yellow and the divalent nature of oxygen; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl
, Alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloa
The group consisting of lucoxy, hydroxyalkyl, alkylenylamino and cyano
A group selected from: R¹⁶And R¹⁹Is optionally Q^bWhere R¹⁶And R^{1 9} More than one at the same time Q^bIs not, Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride, and
C (NR²⁵) NR²³R²⁴A group selected from the group consisting of:²⁰You
And R²¹Are not simultaneously hydroxy, and R ²³ And R²⁴Many one cannot be hydroxy at the same time; R²⁰, R²¹, R²³, R²⁴And R²⁵Are, independently, hydride, al
A group selected from the group consisting of kill and hydroxy; Q^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
A group represented by;

The most specific examples of the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof are: J is O; B is a compound represented by the formula:

[0112]

Embedded image

[Wherein R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently hydride, acetamido, haloacetamide, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino , Alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl,
Alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, groups represented by radical selected from the group consisting of cyano and Q ^b; A is a single covalent bond and (CH (R _{^{15)) pa - (W 7}} ) a group selected from the group consisting of _rr, here, rr is an integer selected from 0 to 1, pa is 0-3
And W ⁷ is N (R ⁷ ); R ⁷ is a group selected from the group consisting of hydride and alkyl; R ¹⁵ is selected from the group consisting of hydride, halo, alkyl and haloalkyl Ψ is NH; M is a group selected from the group consisting of N and R ¹ -C; R ¹ is hydride, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, A group selected from the group consisting of alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R ² is a group represented by Z ⁰ -Q; Z ⁰ is a single covalent bond;

Q is a group selected from the group consisting of aryl and heteroaryl, wherein
One carbon adjacent to the carbon at the binding site may optionally be R⁹Even if
Often, the other carbon adjacent to the carbon at the binding site is optionally R¹³Is replaced by
May be, R⁹Adjacent to and two atoms away from the carbon at the binding site,
R¹⁰May be substituted with¹³, And two atoms from the carbon at the binding site
The detached carbon is optionally R¹²May be substituted with¹⁰And R ¹² All carbons adjacent to both are optionally R¹¹May be replaced by
R⁹, R¹¹, And R¹³But independently, hydride, hydroxy, amino,
Amidino, guanidino, lower alkylamino, alkylthio, alkoxy, al
Killsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamido
Dosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxya
Selected from the group consisting of alkyl, carboxy, carboxamide and cyano
Group; R¹⁰And R¹²But independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkyl, alkoxy, alkoxyamino, amino
Alkyl, hydroxy, amino, lower alkylamino, alkylsulfonamide
, Amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfo
Nil, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboal
From koxy, carboxy, carboxyalkyl, carboxamide and cyano
A group selected from the group consisting of:₂E⁰Is C (O) N (H); Y⁰Is the formula (IV):

[0115]

Embedded image (IV)

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently a group selected from C, N, O, S and a covalent bond, provided that more than one is a covalent bond Is not
K ² is C and more than one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is never O, and more than one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S Is not
When two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and S, one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be a covalent bond, and D ⁵ , D ⁶ , J ⁵ and many more than four of ^{J 6} is a group represented by is not an ^{N]; R 16, R 17} , R 18 and ^{R 19} are independently hydrido, amidino, guanidino, carboxy, halo Alkylthio, alkoxy, hydroxy, amino,
A group selected from the group consisting of lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; R ¹⁶ and R ¹⁹ are preferably by a ^{Q b, where} more than one of ^{R 16} and ^{R 1 9} are never at the same time ^{Q b, Q b} is ^Q be; ^{Q b is, NR 20 R 21, Q be} , where In addition, ^Qbe is a hydride, and C (N
R ²⁵⁾ group is selected from the group consisting of ^{NR 23 R 24; R 20,} R 21, R 23, R 24 and ^{R 25} are independently groups selected from the group consisting of hydrido and alkyl; ^{Q s} Is CH ₂ ;

Other most specific examples of the compounds of formula (I) or pharmaceutically acceptable salts thereof are: J is O; B is hydride, C2-C8 alkyl, C3-C8 Alkenyl,
A group selected from the group consisting of C3-C8 alkynyl and C2-C8 haloalkyl, wherein each member of B is, optionally, any carbon up to 6 atoms from the point of attachment of B to A is R ³² , in one or more radicals of the group consisting of R ^{33, R 34, R 35} and ^{R 36,} which may be substituted; ^{R 32,} R ^33, R ^{34, R 35} and ^{R 36} are independently , Hydride, acetamide, haloacetamide, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl , Carboalkoxy, carboxy, carboxy Bromide, cyano and ^{Q b} group is selected from the group consisting of; is A, a single covalent bond and _{^{(CH (R 15)) pa}} - (W 7) a group selected from _rr, here, rr is 0 An integer selected from 1; pa is an integer selected from 0 to 3; and W ⁷ is N (R ⁷ ); R ⁷ is a group selected from the group consisting of hydride and alkyl; R ¹⁵ is A group selected from the group consisting of hydride, halo, alkyl and haloalkyl; Ψ is NH; M is a group selected from the group consisting of N and R ¹ -C; R ¹ is hydride, hydroxy, hydroxyamino, Amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and halo A group selected from the group consisting of

R²Is Z⁰-Q; Z⁰Is a single covalent bond; Q is a group selected from the group consisting of aryl and heteroaryl, wherein
One carbon adjacent to the carbon at the binding site may optionally be R⁹Even if
Often, the other carbon adjacent to the carbon at the binding site is optionally R¹³Is replaced by
May be, R⁹Adjacent to and two atoms away from the carbon at the binding site,
R¹⁰May be substituted with¹³, And two atoms from the carbon at the binding site
The detached carbon is optionally R¹²May be substituted with¹⁰And R ¹² All carbons adjacent to both are optionally R¹¹May be replaced by
R⁹, R¹¹, And R¹³Is independently hydride, hydroxy, amino,
Amidino, guanidino, lower alkylamino, alkylthio, alkoxy, al
Killsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamido
Dosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxya
Selected from the group consisting of alkyl, carboxy, carboxamide and cyano
Group; R¹⁰And R¹²Is independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkyl, alkoxy, alkoxyamino, amino
Alkyl, hydroxy, amino, lower alkylamino, alkylsulfonamide
, Amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfo
Nil, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboal
From koxy, carboxy, carboxyalkyl, carboxamide and cyano
A group selected from the group consisting of: Y⁰Is the formula (IV);

[0119]

Embedded image (IV)

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently a group selected from C, N, O, S and a covalent bond, provided that more than one is a covalent bond Is not
K ² is C and more than one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is never O, and more than one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S Is not
When two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and S, one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be a covalent bond, and D ⁵ , D ⁶ , J ⁵ and many more than four of ^{J 6} is never a N, ^{however, R 16, R 17, R} 18 and ^{R 1 9} are each independently, each independently, tetravalent nature of carbon , Nitrogen, trivalent sulfur and divalent oxygen are selected; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are independently hydride, amidino , Guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
R ¹⁶ and R ¹⁹ are preferably groups selected from the group consisting of lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; By Q ^b , provided that one of R ¹⁶ and R ¹⁹
Many than one is never at the same time ^{Q b, Q b} is ^Q be; ^{Q b is, NR 20 R 21, Q be} , ^{here, Q BE} hydrido, N ^{(R 26)}
A group selected from the group consisting of C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ) and C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ Is independently a group selected from the group consisting of hydride and alkyl; Q ^s is CH ₂ ;

Other most specific embodiments of the compounds of formula (I) or a pharmaceutically acceptable salt thereof are: wherein J is O; B is from the group consisting of C3-C7 cycloalkyl and C4 heterocyclyl group selected, here, each carbon is optionally may be substituted with R ^33, ring carbon other than the ring carbon of the binding site of B to a is optionally, substituted by oxo Provided that no more than one ring carbon is simultaneously substituted with oxo and that the ring carbon and nitrogen adjacent to the carbon at the point of attachment are optionally
A ring carbon or nitrogen adjacent to the R ⁹ site and 2 atoms from the bond site may be substituted for R ⁹ or R ^13, and may be substituted for R ¹⁰ , adjacent to the R ¹³ site and 2 atoms of the ring carbon or nitrogen from the site may be substituted with R ^12, ring carbon adjacent the binding site 3 atoms and R ¹⁰ sites may be substituted with R ^{1 1,} binding site ring carbon adjacent to the 3 atom and R ¹² sites from may be substituted with R ^33, ring carbon adjacent the binding site 4 atoms and R ¹¹ and R ³³ sites is substituted with R ³⁴ R ⁹ , R ¹¹ and R ¹³ independently represent hydride, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl, a R ¹⁰ and R ¹² are independently hydride, a group selected from the group consisting of alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamide and cyano; , Acetamide, haloacetamide, amidino, guanidino, alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino, alkylsulfonamide, amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxyamide and groups selected from the group consisting of cyano; R ³³ Contact Fine R ³⁴ is, independently, hydride, amidino, guanidino, alkoxy, hydroxy, amino, alkoxy, amino, lower alkylamino, alkylthio, amido sulphonyl, monoalkyl amide sulfonyl, dialkylamido sulfonyl, alkyl, halo, haloalkyl, haloalkoxy , hydroxyalkyl, carboalkoxy, carboxy, groups selected from the group consisting of carboxamide and cyano; R ³³ is may be optionally Q ^b group;

A is a group 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, pa Is 0-
An integer selected from 3 and W ⁷ is N (R ⁷ ); R ⁷ is a group selected from the group consisting of hydride, hydroxy and alkyl; R ¹⁵ is a group consisting of hydride, halo, alkyl and haloalkyl Ψ is NH; M is a group selected from the group consisting of N and R ¹ -C; R ¹ is hydride, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy A group selected from the group consisting of, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R ² is Z ⁰ -Q; Z ⁰ is a single covalent bond; And a group selected from the group consisting of:
The carbon adjacent to the carbon at the binding site may be optionally substituted with R ⁹ ,
Other carbon adjacent to the carbon binding sites, optionally, may be substituted by R ^13, the carbon of the 2 atoms from the carbon of the adjacent and binding sites R ⁹ is optionally substituted on R ^{1 0} And two carbons from the carbon adjacent to and at the binding site to R ¹³ may be optionally substituted with R ¹² , and all carbons adjacent to both R ¹⁰ and R ^{12 at} the bonding site are optionally may be substituted with ^{R 11;} K ^is, CH 2; ^{E 0} is, C (O) N (H ); is ^{Y 0,} the formula (IV):

[0123]

Embedded image (IV)

Wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently a group selected from C, N, O, S and a covalent bond, provided that more than one is a covalent bond Is not
K ² is C and more than one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is never O, and more than one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is S Is not
If two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and S, one of D ⁵ , D ⁶ , J ⁵ and J ⁶ must be a covalent bond, and D ⁵ , D ⁶ , J ⁵ and many more than four of ^{J 6} is never a N, ^{however, R 16, R 17, R} 18 and ^{R 1 9} are each independently, each independently, tetravalent nature of carbon , Which is selected so as to maintain the trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; and R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are each independently Hydride, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
R ¹⁶ and R ¹⁹ are groups selected from the group consisting of lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkylenylamino and cyano; , Optionally Q ^b , provided that one of R ¹⁶ and R ¹⁹
Many than one is, that they are not simultaneously ^{Q b, Q b} is ^Q be; ^{Q b is, NR 20 R 21, Q be} , ^{here, Q BE} is hydrido, and ^{C (NR} 25) NR ²³ group is selected from the group consisting of ^{R 24; R 20, R 21} , R 23, R 24 and ^{R 25} are independently groups selected from the group consisting of hydrido and alkyl; ^{Q s} is _CH 2; It is.

As a specific example represented by the formula (I), a compound represented by the formula (IS):

[0126]

Embedded image (IS) wherein B is:

[0127]

Embedded image

Wherein R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently hydride, amidino, guanidino, carboxy, methyl, ethyl, isopropyl, propyl, methoxy, ethoxy, isopropoxy, Propoxy, hydroxy, amino,
Methoxyamino, ethoxyamino, acetamide, trifluoroacetamide,
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, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropa Noyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, 2,2,2-
Trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N- methylamide carbonyl, N, is selected N- dimethylamide carbonyl from the group consisting of cyano and Q ^b B is hydride, 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-butenyl, 1-methyl-3 -Butenyl, 1-methyl-2-butynyl, 3-pen Le, 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-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, 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-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 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-heptynyl, 1-methyl-3-heptynyl, 1-methyl- 4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptenyl, 1-methyl-
3-heptynyl, 1-methyl-4-heptynyl, 1-methyl-5-heptynyl,
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-pentynyl, 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- A group selected from the group consisting of trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl and 3,3,3-trifluoropropyl, wherein each member of B is optionally A 5 from the binding site of B to
At all carbons up to the atom, one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ may be substituted;

B is optionally cyclopropyl, cyclobutyl, oxetan-2-yl,
Oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiethane-2-yl, thiethane-3-yl, cyclopentyl, cyclohexyl, adamantyl, norbornyl, 3-trifluoromethylnor bornyl, bicyclo [3.1.0] hexane-6-yl, radical selected from the group consisting of cycloheptyl and cyclooctyl, in which each carbon is optionally, be substituted by R ³³ Optionally, the ring carbon and nitrogen adjacent to the carbon at the binding site may be optionally substituted with R ⁹ or R ¹³ , and 2 carbon atoms adjacent to the R ⁹ site and 2 atoms from the carbon at the bonding site may be optionally substituted. It may be substituted with R ^10, the carbon of the 2 atoms from the carbon of the adjacent and binding sites R ¹³ sites, if desired, in R ¹² May be ^{conversion; R 9, R 10, R} 11, R 12 and ^{R 13} are independently 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, methanesulfonamide, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1- Hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1
-Hydroxyethyl, 2,2,2-trifluoro-1-trifluoromethyl-1-
A group selected from the group consisting of hydroxyethyl, carboxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethoxyamidocarbonyl and cyano;

A is a single covalent bond, O, S, NH, N (CH ₃ ), N (OH), C (O), C
H 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 C
_{H 2, CH 3 CHCH 2,} CF 3 CHCH 2, CH 3 CC (O) CH 2, CF 3 CC (O) CH 3, CH 2 C (O) CCH 3, CH 2 C (O) CCF 3, CH A group selected from the group consisting of ₂ CH ₂ C (O) and CH ₂ (O) CCH ₂ ; A is CH ₂ N (CH ₃ ), CH ₂ N (CH ₂ CH ₃ ), CH ₂ A group selected from the group consisting of CH ₂ N (CH ₃ ), CH ₂ CH ₂ N (CH ₃ ) and CH ₂ CH ₂ N (CH ₂ CH ₃ ), where B is hydride; M is N and group is selected from the group consisting of ^{R 1} -C; R ¹ is hydrido, hydroxy, amino, thiol, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, methylamino, dimethylamino, Ano, 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
A group selected from the group consisting of tetrafluoroethoxy, fluoro, chloro and bromo;

R ² is a group represented by Z ⁰ -Q; Z ⁰ is a single covalent bond, O, 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 groups selected from the group consisting of _{(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 1,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazole-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-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl,
1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4
-A group selected from the group consisting of triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,3-triazin-4-yl and 1,2,3-triazin-5-yl here, one carbon adjacent to the carbon binding sites, optionally, it may be substituted by R ^9, the other carbon adjacent to the carbon binding sites, optionally substituted on R ^{1 3} The carbon adjacent to the R ⁹ position and 2 atoms away from the carbon at the bonding site may be optionally substituted with R ¹⁰ , and adjacent to the R ¹³ position and 2 carbons from the carbon at the bonding site. The carbon away from the atom may be optionally substituted with R ¹² , and all carbons adjacent to both R ¹⁰ and R ¹² may be optionally substituted with R ¹¹ ; K is CH ^4a , wherein CH ^4a is methyl, ethyl, propyl E ⁰ is a group selected from the group consisting of isopropyl, hydroxymethyl, 1-hydroxyethyl, methoxymethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoromethyl, methylthiomethyl and hydride; single covalent bond, C (O) N (H ), (H) NC (O) and _{S (O) 2 N (H} ); Y 0 is formula;

[0132]

Embedded image

Embedded image

Embedded image A group selected from the group consisting of:

R¹⁶, R¹⁷, R¹⁸And R¹⁹Is independently hydride, methyl, ethi
Isopropyl, propyl, amidino, guanidino, carboxy, methoxy,
Ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino
, Ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-
N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio
E, isopropylthio, trifluoromethylthio, methylsulfinyl, ethyl
Sulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl,
N-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentane
Fluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroeth
Xy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfo
Nyl, N, N-dimethylamidosulfonyl, acetyl, propanoyl, trifur
Oroacetyl, pentafluoropropanoyl, hydroxymethyl, 1-hydroxy
Ciethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxy
A group selected from the group consisting of ethyl and cyano; R¹⁶And R¹⁹Is optionally Q^bWhere R¹⁶And R^{1 9} More than one at the same time Q^bIs not, Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride and C (N
R²⁵) NR²³R²⁴And N (R²⁶) C (NR²⁵) NR²³R²⁴From
A group selected from the group consisting of:²⁰And R²¹More than one of the
In addition, being hydroxy, N-methylamino and N, N-dimethylamino
No, R²³And R²⁴More than one is simultaneously hydroxy, N-methyl
Never amino and N, N-dimethylamino; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
, Methyl, ethyl, propyl, butyl, isopropyl, hydroxy, 2-amido
Noethyl, 2- (N-methylamino) ethyl and 2- (N, N-dimethylamido)
No) a group selected from the group consisting of ethyl;^sIs a single covalent bond, CH₂, CH₂CH₂, CH₃CH, CF₃CH, CH ₃ CHCH₂, CF₃CHCH₂, CH₂(CH₃) CH, CH = CH, CF =
CH, C (CH3) = CH, CH = CHCH₂, CF = CHCH₂, C (CH₃ ) = CHCH₂, CH₂CH = CH, CH₂CF = CH, CH₂C (CH₃) =
CH, CH₂CH = CHCH₂, CH₂CF (CH₃) = CHCH₂, CH₂C
(CH₃) = CHCH₂, CH₂CH = CHCH₂CH₂, CH₂CF = CHC
H₂CH₂And CH₂C (CH₃) = CHCH₂CH₂Selected from the group consisting of
Or a pharmaceutically acceptable salt thereof.

As a more specific example of Formula (I), Formula (I-MPS):

[0135]

Embedded image

[Wherein B is a compound of the formula:

Embedded image

(Wherein R³², R³³, R³⁴, R³⁵And R³⁶, Independently, hydride
, Amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy,
Propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetoa
Amide, trifluoroacetamide, N-methylamino, dimethylamino, NE
Tylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl
Pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pe
N-fluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoro
Ethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidos
Ruphonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydro
Xyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxy
Ethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methyl
Cylamide carbonyl, N, N-dimethylamidocarbonyl, cyano and Q^b
A group selected from the group consisting of: A is a single covalent bond, NH, N (CH₃), N (OH), CH₂, CH₃CH,
CF₃CH, NHC (O), N (CH₃) C (O), C (O) NH, C (O) N
(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂And CF ₃ CHCH₂A group selected from the group consisting of: Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride, and
C (NR²⁵) NR²³R²⁴A group selected from the group consisting of:²⁰You
And R²¹Is not simultaneously hydroxy, and R²³You
And R²⁴No more than one is simultaneously hydroxy; R²⁰, R²¹, R²³, R²⁴And R²⁵The, independently, hydride, meth
From the group consisting of ethyl, propyl, butyl, isopropyl and hydroxy
Group selected; Q^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
Or a pharmaceutically acceptable salt thereof.

Another more specific example of formula (I) is represented by formula (I-MPS):

[0139]

Embedded image (I-MPS)

[Wherein B is hydride, 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,
-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-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, 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, 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-triphenyl A group selected from the group consisting of fluoropropyl,
Wherein each member of B is, optionally, one of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ^{36 wherein} any carbon containing up to 5 atoms from the bonding site of B to A is Or may be substituted with more groups;

R³², R³³, R³⁴, R³⁵And R³⁶Are, independently, hydride,
Dino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propo
Xy, hydroxy, amino, methoxyamino, ethoxyamino, acetamide,
Trifluoroacetamide, N-methylamino, dimethylamino, N-ethylamine
Mino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pen
Tafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentaf
Fluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy
Si, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl
, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl
Chill, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl
, Methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methyla
Midocarbonyl, N, N-dimethylamidocarbonyl, cyano and Q^bConsists of
A is a single covalent bond, NH, N (CH₃), N (OH), CH₂, CH₃CH,
CF₃CH, NHC (O), N (CH₃) C (O), C (O) NH, C (O) N
(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂And CF ₃ CHCH₂A is optionally CH₂N (CH₃), CH₂N (CH₂CH₃), CH₂ CH₂N (CH₃), CH₂CH₂N (CH₃) And CH₂CH₂N (CH₂ CH₃Q is a group selected from the group consisting of:^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride and C (N
R²⁵) NR²³R²⁴And N (R²⁶) C (NR²⁵) NR²³R²⁴From
A group selected from the group consisting of:²⁰And R²¹More than one of the
Without being hydroxy, R²³And R²⁴More than one of the
Cannot be hydroxy; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
Of methyl, ethyl, propyl, butyl, isopropyl and hydroxy
A group selected from the group consisting of^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
Or a pharmaceutically acceptable salt thereof.

Another even more specific example of formula (I) is represented by formula (I-PMS):

[0143]

Embedded image (I-MPS)

[Wherein B is, if desired, cyclopropyl, cyclobutyl, oxetane-3-
Yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl,
Thiaethane-3-yl, cyclopentyl, cyclohexyl, norbornyl, bis
Selected from the group consisting of clo [3.1.0] hexane-6-yl and cycloheptyl
Wherein each carbon is optionally substituted with R³³May be replaced by
, The ring carbon and the nitrogen adjacent to the carbon at the point of attachment are optionally R⁹Or R^{1 3} A carbon atom adjacent to the binding site and two atoms away from the binding site
Element or nitrogen may optionally be R¹⁰May be substituted with¹³Next to the rank
, A ring carbon or nitrogen two atoms away from the bond, optionally¹²Replaced by
A is a single covalent bond, NH, N (CH₃), N (OH), CH₂, CH₃CH,
CF₃CH, NHC (O), N (CH₃) C (O), C (O) NH, C (O) N
(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂And CF ₃ CHCH₂A group selected from the group consisting of: R³³Are independently hydride, amidino, guanidino, carboxy,
Si, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxya
Mino, ethoxyamino, acetamide, trifluoroacetamide, N-methyl
Amino, dimethylamino, N-ethylamino, methylthio, ethylthio, isop
Ropirthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Oroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy
1,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amide
Sulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl
, Hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2
2-trifluoro-1-hydroxyethyl, methoxycarbonyl, amide carb
Nyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, shea
No and Q^bA group selected from the group consisting of: Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride, and
C (NR²⁵) NR²³R²⁴A group selected from the group consisting of:²⁰You
And R²¹Is not simultaneously hydroxy, and R²³You
And R²⁴No more than one is simultaneously hydroxy; R²⁰, R²¹, R²³, R²⁴And R²⁵The, independently, hydride, meth
From the group consisting of ethyl, propyl, butyl, isopropyl and hydroxy
Group selected; Q^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
Wherein B is a non-aromatic ring substituent or a pharmaceutically acceptable compound thereof.
salt.

A more specific example (I-MPS) is:

[0146]

Embedded image

M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, hydroxy, amino, amidino, hydroxyamino,
Nomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl
, Ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Roethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy
Siethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy,
Consists of 1,1,2,2-tetrafluoroethoxy, fluoro, chloro and bromo
A group selected from the group consisting of: R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, O, S, NH and CH₂A group selected from the group consisting of
Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2
-Pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazo
Ryl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl
Ryl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyridyl
Midinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridinyl
A group selected from the group consisting of dazinyl and 1,3,5-triazin-2-yl,
Here, one carbon adjacent to the carbon at the bonding site is optionally R⁹Is replaced by
And other carbons adjacent to the carbon at the site of attachment may optionally be R¹³Put in
May be replaced by R⁹Adjacent to the position and two atoms away from the carbon at the binding site
, If desired, R¹⁰May be substituted with¹³Adjacent to the position
Carbon two atoms away from carbon may optionally be¹²May be substituted with ¹⁰ And R¹²All carbons adjacent to both are optionally R¹¹Is replaced by
R⁹, R¹¹And R¹³Is independently hydride, amidino, guanidino,
Carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy,
Isopropoxy, propoxy, hydroxy, amino, N-methylamino, N, N
-Dimethylamino, N-ethylamino, methylthio, ethylthio, isopropyl
Thio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Chill, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy, 1,
1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfo
Amide, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethyl
Amidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy
Ethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,
N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and cyano
A group selected from the group consisting of: R¹⁰And R¹²Is hydride, amidino, guanidino, carboxy, cal
Boxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy
, Isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxy
Cyamino, acetamide, trifluoroacetamide, aminomethyl, 1-amido
Noethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethyl
Amino, methanesulfonamide, amidosulfonyl, N-methylamidosulfoni
, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl
Chill, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl
, Methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methyla
Midocarbonyl, N, N-dimethylamidocarbonyl, fluoro, chloro, bromine
A group selected from the group consisting of mo and cyano; Y⁰Is:

[0148]

Embedded image

Embedded image

Embedded image A group selected from the group of formulas consisting of:

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are independently hydride, 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, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3 , 3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoromethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl , 1-hydroxyethyl, 2-hydroxyethyl, 2,2
, 2 groups selected from the group consisting of-trifluoro-1-hydroxyethyl, and cyano; ^{R 16} and ^{R 19,} optionally a ^{Q b, however, R 16} and ^{R 19} 1
Salts often than one may not be at the same time Q ^b, Q ^b is acceptable compound or pharmaceutical of the present invention represented by Q ^BE].

The most detailed example of formula (I) is represented by formula (I-EMPS):

[0151]

Embedded image (I-EMPS, where B is aromatic)

[Wherein B is;

[0153]

Embedded image

Wherein R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently hydride, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy,
Amino, N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, group amide carbonyl, carboxy, represented by groups) selected from the group consisting of cyano and ^{Q b;} A is a single covalent _{bond, NH, N (CH 3)} , CH 2, CH 3 CH and _CH 2 C
Group is selected from the group consisting of H _2; ^{Q b is NR} 20 ^{R 21} and ^C (NR ²⁵⁾ group selected from the group consisting of ^NR 23 ^{R 24,} provided that, ^{Q b} is bonded directly to a carbon atom R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are each independently a group selected from the group consisting of hydride, methyl and ethyl; Q ^s is represented by a single covalent bond, CH ₂ ] A compound or a pharmaceutically acceptable salt thereof.

Another most specific example of formula (I) is represented by formula (I-EMPS):

[0156]

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

[Wherein B is hydride, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 2-butynyl, sec-butyl, te
rt-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-heptynyl, 3-heptynyl, 4-heptynyl, 5-
Heptynyl, 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-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl and 3,3,3- A group selected from the group consisting of trifluoropropyl, wherein
Each member of B is optionally one or more of the group consisting of R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ , wherein any carbon containing up to 5 atoms from the site of attachment of B to A is R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently hydride, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N- Methylamino, dimethylamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carbonyl , group A is selected from the group consisting of cyano and ^{Q b} is a single covalent bond, NH, N (CH ₃ ), CH ₂ , CH ₃ CH and CH ₂ C
Group is selected from the group consisting of H _2; A is _{optionally, 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 A group selected from the group consisting of (CH ₂ CH ₃ ), wherein B is a hydride; Q ^b is NR ²⁰ R ²¹ , C (NR ²⁵ ) NR ²³ R ²⁴ and N (R ²⁶ )
A group selected from the group consisting of C (NR ²⁵ ) NR ²³ R ^{24 wherein} the Q ^b group is directly bonded to a carbon atom; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are A group independently selected from the group consisting of hydride, methyl and ethyl; Q ^s is a compound represented by CH ₂ ], wherein B is a non-aromatic ring substituent or a pharmaceutically acceptable group thereof. salt

A more specific example of formula (I) is represented by formula (I-EMPS):

[0159]

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

[Wherein B is, if desired, cyclopropyl, cyclobutyl, oxetane-3-
Yl, azetidin-3-yl, Chiaetan-3-yl, radical selected from the group consisting of cyclopentyl and cyclohexyl, with the proviso that each carbon can optionally be substituted in R ^33, the carbon binding sites The ring carbon and nitrogen adjacent to may be optionally substituted with R ⁹ or R ^13, and the ring carbon or nitrogen adjacent to and two atoms away from the binding site may optionally be substituted with R ¹⁰ A ring carbon or nitrogen adjacent to the R ¹³ position and 2 atoms away from the bond may optionally be substituted with R ¹² ; R ³³ is independently hydride, amidino , Guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, carboxy, amino, N-methylamino, dimethylamino, methylthio, ethylthio, tri Ruoromechiru, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amide sulfonyl, N- methylamide sulfonyl, hydroxymethyl, amido carbonyl,
Group is selected from the group consisting of cyano and ^{Q b;} A is a single covalent _{bond, NH, N (CH 3)} , CH 2, CH 3 CH and _CH 2 C
Group is selected from the group consisting of H _2; ^{Q b is NR} 20 ^{R 21} and ^C (NR ²⁵⁾ group selected from the group consisting of ^NR 23 ^{R 24,} provided that, ^{Q b} group is bonded directly to a carbon atom R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are each independently a group selected from the group consisting of hydride, methyl and ethyl; Q ^s is a compound represented by CH ₂ ] And B are non-aromatic ring substituents, or pharmaceutically acceptable salts thereof.

The most specific example (I-EMPS) has the formula:

[0162]

Embedded image

Wherein M is a group selected from the group consisting of N and R ¹ -C; R ¹ is hydride, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, A group selected from the group consisting of trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro and chloro; R ² is a group represented by Z ⁰ -Q; Z ⁰ is a single covalent bond Q is a group selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazoyl, 3-isoxazoyl, 2-pyridyl and 3-pyridyl; carbon adjacent to the site of carbon, if desired, may be substituted by R ^9, the other carbon adjacent to the carbon binding site Optionally may be substituted by R ^13, adjacent to R ^9, carbon distant 2 atoms from the carbon of the binding site is optionally, may be substituted in R ^10, adjacent to the R ^13, carbon away 2 atoms from the carbon of the binding site is optionally, may be substituted with R ^12, all carbon adjacent binding sites of both R ¹⁰ and R ¹² are optionally substituted with R ¹¹ R ⁹ , R ¹¹ , and R ¹³ are independently hydride, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N, N-dimethylamino, methylthio, trifluoromethyl , Pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfo Nil, hydroxymethyl, 1
A group selected from the group consisting of -hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy and cyano; R ¹⁰ and R ¹² are independently hydride, amidino, amidocarbonyl,
N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2, 2,2-trifluoroethyl, trifluoroacetamide, aminomethyl, N-methylamino, dimethylamino, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo and cyano group is selected from the group consisting of; Y ⁰ is:

[0164]

Embedded image

Embedded image

Embedded image Selected from the group of formulas consisting of

R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are independently hydride, 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, tri Fluoromethoxy, fluoro, chloro, amidosulfonyl, N-
A group selected from the group consisting of amidosulfonyl, hydroxymethyl, carboxy and cyano] or a pharmaceutically acceptable salt thereof.

The compounds of the present invention find use in anticoagulant therapy for the treatment and prevention of thrombotic conditions, including coronary and cerebrovascular disease. The compounds of the present invention can be used for serine protease inhibition involving the coagulation cascade and factors II, VII, VII, IX, X, XI or XII. Compounds of the invention can inhibit the formation of platelet aggregates, fibrin, and embolism in mammals, blood, blood products and mammalian organs. In addition, the present compound, in mammals, unstable angina, intractable angina, myocardial infarction, transient cerebral ischemic attack, atrial fibrillation, thrombotic stroke,
It can be used to treat or prevent embolic stroke, deep vein thrombosis, disseminated intravascular blood coagulation, increased fibrin in the eye, and reocclusion or restenosis of reopened blood vessels. The compounds can also be used for prophylactic treatment of subjects at risk of developing such a disease. The compounds can be used for low risk of atherosclerosis (CVA).
Further, the compound represented by the formula (I) can be used for prevention of cerebrovascular disorder or stroke. In addition, the compounds can be used in the treatment of humans, and can be used in veterinary treatment of companion animals, including mammals, rodents and the like, and exotic animals and livestock.
More preferred animals include horses, dogs and cats. As a further embodiment of the present invention, the novel compounds are selected from the compounds shown in Examples 1 to 19 and Table 1.

The generic terms used in the description of the compounds herein are clearly defined. Unless otherwise specified, basic elemental symbols are used to refer to a specific type. The symbol "C" means a carbon atom. The symbol "O" means an oxygen atom. The symbol "N" means a nitrogen atom. The symbol "P" means a phosphorus atom. The symbol "S" means a sulfur atom. The symbol "H" means a hydrogen atom. 2
Element symbols written with two symbols are used as definitions of elements in the periodic table (ie, Cl means chlorine and Se means selenium).

As used herein, the term “alkyl” is used alone or “haloalkyl”
And in other terms, such as "alkylthio", means an acyclic alkyl radical containing 1 to about 10, preferably 3 to about 8, more preferably 3 to about 6 carbon atoms. The alkyl radical may be optionally substituted by the following groups. For example, methyl, ethyl, chloroethyl, hydroxyethyl, n
-Propyl, oxopropyl, isopropyl, n-butyl, cyanobutyl, isobutyl, sec-butyl, tert-butyl, pentyl, aminopentyl, is
Radicals including o-amyl, hexyl, octyl and the like.

The term “alkenyl” refers to an unsaturated acyclic hydrocarbon radical containing at least one double bond. Such alkenyl radicals contain 2 to about 10, preferably 3 to about 8, more preferably 3 to about 6 carbon atoms. The alkenyl radical may be optionally substituted by the following groups. For example, suitable alkenyl radicals are propenyl, 2-chloropropenyl, buten-1-yl, isobutenyl, penten-1-yl, 2-methylbuten-1-yl, 3-methylbuten-1-yl, hexen-1-. Yl, 3-hydroxyhexen-1-yl, hepten-1-yl and octen-1-yl and the like.

The term “alkynyl” refers to an unsaturated acyclic hydrocarbon radical containing one or more triple bonds, such radicals being from 2 to about 10, preferably 3
From about 8, more preferably from 2 to about 6 carbon atoms. The alkynyl radical may be optionally substituted by the following groups. For example, suitable alkynyl radicals are ethynyl, propynyl, hydroxypropynyl, butyn-1-yl, butyn-2-yl, pentyn-1-yl, pentyn-2-yl, 4-methoxypentyn-2-yl, -Methylbutyn-1-yl, hexyn-1-yl, hexyn-2-yl, hexyn-3-yl, 3,3-dimethylbutyn-1-yl radical and the like.

The term “hydride” denotes one hydrogen atom (H). The hydride radical may, for example, bond to an oxygen atom to form a “hydroxy” radical, one hydride radical may bond to a carbon atom to form a “methine” radical —CH ＝, or The two hydride radicals combine with a carbon atom to form "methylene"
A (—CH ₂ —) radical may be formed. The term "carbon" radical refers to a carbon atom that has no covalent bonds and is capable of forming four covalent bonds. The term “cyano” radical denotes a carbon atom in which three of the four covalent bonds are shared by a nitrogen atom.

The term “hydroxyalkyl” includes radicals wherein any one or more of the alkyl carbon atoms is replaced with a hydroxy as described above. Specifically, it includes monohydroxyalkyl, dihydroxyalkyl and polyhydroxyalkyl radicals.

The term “alkanoyl” includes radicals in which any one or more of the terminal alkyl carbon atoms has been replaced by one or more of the carbonyl radicals described below. Specifically, it includes monocarbonylalkyl and dicarbonylalkyl radicals. For example, monocarbonylalkyl radicals include formyl, acetyl, and pentanoyl. For example, dicarbonylalkyl radicals include oxalyl, malonyl and succinyl.

The term “alkylene” radical refers to a straight-chain or branched radical having from 1 to about 10 carbon atoms and having points of attachment to two or more covalent bonds. For example, such radicals are methylene, ethylene, methylethylene and isopropylidene. The term "alkenylene" radical refers to a straight-chain or branched radical having from 2 to about 10 carbon atoms, at least one double bond, and a point of attachment to two or more covalent bonds. For example, such a radical is 1,1-vinylidene _(CH 2 = C), 1,2-vinylidene (-CH = CH-) and 1,4-butadienyl (-CH = CH-CH = CH- ) is there.

The term “halo” means a halogen, such as a fluorine, chlorine, bromine or iodine atom. The term “haloalkyl” includes radicals wherein any one or more of the alkyl carbon atoms is replaced with the above halo. Specifically, it includes monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. For example, a monohaloalkyl radical may have a bromine, chlorine or fluorine atom in the radical. A dihalo radical may have two or more identical halo atoms or a combination of different halo atoms, and a polyhaloalkyl radical may have more than two identical halo atoms or a combination of this different halo radical. Is also good.
More preferred haloalkyl radicals are "lower haloalkyl" radicals having one to about six carbon atoms. For example, such haloalkyl is fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trifluoroethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, Including difluoropropyl, dichloroethyl and dichloropropyl.

The term “hydroxyhaloalkyl” includes radicals wherein any one or more of the haloalkyl carbons is substituted with a hydroxy as described above. For example, a “hydroxyhaloalkyl” radical includes hexafluorohydroxypropyl. The term "haloalkylene" radical includes an alkylene radical wherein any one or more of the alkylene carbon atoms is replaced with the above halo. A dihaloalkylene radical may have two or more identical halo atoms or a combination of different halo atom radicals, and a polyhaloalkylene radical may have more than two identical halo atoms or different halohalo radicals. You may have a combination. More preferred haloalkylene radicals are "lower haloalkylene" radicals having one to about six carbon atoms. For example, "haloalkylene" radicals include difluoromethylene, tetrafluoroethylene, tetrachloroethylene, alkyl-substituted monofluoromethylene, and aryl-substituted trifluoromethylene.

The term “haloalkenyl” refers to a straight or branched radical having from 1 to about 10 carbon atoms, wherein any one or more of the alkenyl carbon atoms is substituted with the halo described above. Dihaloalkenyl radicals may have two or more identical or different combinations of halo atoms, and polyhaloalkenyl radicals may have two or more identical or different combinations of halo atoms. You may have one.

The terms “alkoxy” and “alkoxyalkyl” include straight-chain or branched oxy-containing radicals having an alkyl portion of 1 to about 10 carbon atoms, such as a methyl radical. Also, the term “alkoxyalkyl” has one or more alkoxy radicals attached to the alkyl radical, forming monoalkoxyalkyl and dialkoxyalkyl radicals. More preferred alkoxy radicals are "lower alkoxy" having 1 to 6 carbon atoms. For example, such radicals include methoxy, ethoxy, propoxy, butoxy, isopropoxy and tert-butoxyalkyl. Further, the "alkoxy" radical is
One or more of the halo atoms such as fluorine, chlorine or bromine may be substituted to provide “haloalkoxy” and “haloalkoxyalkyl”. For example,
Such haloalkoxy radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy, difluoromethoxy, trifluoroethoxy, fluoroethoxy, tetrafluoroethoxy, pentafluoroethoxy and fluoropropoxy. For example, such haloalkoxyalkyl radicals include fluoromethoxymethyl, chloromethoxyethyl, trifluoromethoxymethyl, difluoromethoxyethyl and trifluoroethoxymethyl.

The terms “alkenyloxy” and “alkynyloxyalkyl” include oxy-containing radicals having an alkenyl portion of from 2 to about 10 carbon atoms, such as an ethenyloxy or propenyloxy radical. The term "alkenyloxyalkyl" also includes alkenyl radicals having one or more alkenyloxy radicals attached to the alkyl radical, forming monoalkenyloxyalkyl and dialkenyloxyalkyl radicals. And preferably, the alkenyloxy radical is a "lower alkenyloxy" radical having 2 to 6 carbon atoms. For example, such radicals include ethenyloxy, propenyloxy, butenyloxy and isopropenyloxyalkyl. Further, an "alkenyloxy" radical may be substituted on one or more halo atoms such as fluorine, chlorine or bromine to provide a "haloalkenyloxy" radical. For example, such radicals include trifluoroethenyloxy, fluoroethenyloxy, difluoroethenyloxy and fluoropropenyloxy.

The term “haloalkoxyalkyl” also includes alkyl radicals having one or more haloalkoxy radicals attached to the alkyl radical, forming monohaloalkoxyalkyl and dihaloalkoxyalkyl radicals.
Also, the term “haloalkenyloxy” includes oxygen radicals that have one or more haloalkenyloxy radicals attached to an oxygen radical and form monohaloalkenyloxy and dihaloalkenyloxy radicals. Also, the term "haloalkenyloxyalkyl" includes alkyl radicals having one or more haloalkenyloxy radicals attached to the alkyl radical, forming monohaloalkenyloxyalkyl and dihaloalkenyloxyalkyl radicals.

The term “alkylenedioxy” radical refers to an alkylene radical having at least two oxygens attached to one alkylene group. For example, "alkylenedioxy" radicals include methylenedioxy, ethylenedioxy, alkyl-substituted methylenedioxy, and aryl-substituted methylenedioxy. The term "haloalkylenedioxy" radical refers to a haloalkylene radical having at least two oxy groups attached to the haloalkyl group. For example, "haloalkylenedioxy" radicals include difluoromethylenedioxy, tetrafluoroethylenedioxy, tetrachloroethylenedioxy, alkyl-substituted monofluoromethylenedioxy and aryl-substituted monofluoromethylenedioxy.

The term “aryl”, alone or in combination, signifies a carbocyclic aromatic system comprising one, two or three rings, wherein such a ring is bonded to another pair Or may be condensed. The term “fused” means that there is a second ring (ie, attached or formed) that has two common (ie, shared) atoms with the first ring. The term “fuse” is synonymous with the term “condence”. The term "aryl" includes aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl. The term "perhaloaryl" includes aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl, where the aryl radical has been replaced by three or more of the above halo radicals.

The term “heterocyclyl” embraces 4-15 membered saturated and partially saturated heteroatom-containing ring radicals, wherein at least one ring atom selected from carbon, nitrogen, sulfur and oxygen is a heteroatom. It means the atom "C4-C15 heterocyclyl". A heterocyclyl radical may include one, two, or three rings, wherein the rings connect or fuse the other of the pair. For example, a saturated heterocyclic radical is a saturated 3-6 membered heteromonocyclic group containing 1-4 nitrogen atoms [eg, pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.]; 1-2 oxygen atoms and 1-2 A 3-6 membered heteromonocyclic group containing three nitrogen atoms [eg, morpholinyl and the like]; a saturated 3-6 membered heteromonocyclic group containing 1-2 sulfur atoms and 1-3 nitrogen atoms [ For example,
Thiazolidinyl, etc.]. For example, partially saturated heterocyclyl radicals include dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole. Without limitation, heterocyclic radicals include, for example, 1,3-dioxolanyl, 2H-pyranyl, 4H-pyranyl, piperidinyl, 1,4-dioxanyl, morpholinyl, 1,4-dithianyl, thiomorpholinyl, and the like.

The term “heteroaryl” is selected from carbon, nitrogen, sulfur and oxygen.
Includes fully unsaturated heteroatom-containing cyclic aromatic radicals having 15 members and at least one ring atom being a heteroatom. Heteroaryl radicals may contain one, two or three rings that can be attached or fused to the other of the pair. For example, a "heteroaryl" radical is, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl,
Pyridazinyl, triazoyl [eg, 4H-1,2,4-triazoyl, 1H
-1,2,3-triazoyl, 2H-1,2,3-triazoyl and the like], tetrazoyl [for example, 1 to 4 such as 1H-tetrazoyl, 2H-tetrazoyl and the like]
Unsaturated 5- or 6-membered heteromonocyclyl group containing two nitrogen atoms, such as indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzothiazoyl, tetrazolopyridazinyl [eg tetrazolo [1,5 -B] pyridazinyl etc.] and unsaturated condensed heterocyclic groups containing 1 to 5 nitrogen atoms, and 3 to 6 membered heteromonocycles having an oxygen atom such as pyranyl, 2-furyl, 3-furyl and the like. Click groups, for example 2-thienyl,
Unsaturated 5- to 6-membered sulfur-containing heteromonocyclic groups such as 3-thienyl and the like, for example, oxazolyl, isoxazolyl, oxadiazolyl [for example, 1,2
, 4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.] and unsaturated 5- to 6-membered heteromonomers containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms Cyclic groups, one or two oxygen atoms and one to two
Unsaturated condensed heterocyclic groups containing three nitrogen atoms, such as thiazolyl,
Unsaturated 5-6 membered heteromonocyclic containing 1-2 sulfur and 1-3 nitrogen atoms, such as thiadiazolyl [eg, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, etc.] Groups, unsaturated fused heterocyclic groups containing 1-2 sulfur atoms and 1-3 nitrogen atoms [eg benzothiazolyl, benzothiadiazolyl, etc.] and the like. The term also includes radicals in which a heterocyclic radical condenses with an aryl radical. For example, such condensed bicyclic radicals include benzofuran, benzothiophene, and the like. The above “heterocyclic” group may be substituted with the following 1 to 3 substituents. Preferably, the heterocyclic radical comprises a 5-12 membered condensed or non-condensed radical. For example and without limitation, heteroaryl radicals include pyrrolyl, pyridinyl, pyridyloxy, pyrazolyl, triazolyl, pyrimidinyl, pyridazinyl, oxazolyl, thiazolyl, imidazolyl, indolyl, thiophenyl, furanyl, tetrazonyl, 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 -Including tritianil, benzo (b) thiophenyl, benzimidazolyl, quinolinyl, tetraazolyl and the like.

The term “sulfonyl”, whether used alone or in combination with other terms, such as alkylsulfonyl, denotes a divalent radical —SO ₂ —, respectively. “Alkylsulfonyl” includes the above alkyl radicals that bind to a sulfonyl radical. “Alkylsulfonylalkyl” includes an alkylsulfonyl radical bonded to the above alkyl radical. “Haloalkylsulfonyl” includes the haloalkyl radicals described above, which bind to a sulfonyl radical. “Haloalkylsulfonylalkyl” includes haloalkylsulfonyl radicals bonded to the above alkyl radicals. The term "aminosulfonyl" includes an amino radical that binds to a sulfonyl radical.

The term “sulfinyl”, whether used alone or in combination with other terms, such as alkylsulfonyl, denotes a divalent radical —S (O) —, respectively. “Alkylsulfinyl” includes the above alkyl radicals that bind to a sulfinyl radical. “Alkylsulfinylalkyl” includes an alkylsulfinyl radical bonded to the above alkyl radical. “Haloalkylsulfinyl” is
Includes the haloalkyl radicals described above which bind to a sulfinyl radical. “Haloalkylsulfinylalkyl” includes haloalkylsulfinyl radicals bonded to the above alkyl radicals.

[0187] The term "aralkyl" includes aryl-substituted alkyl radicals. Preferably,
Aryl radicals are "lower aralkyl" radicals having an aryl radical, having from one to six carbon atoms, attached to the alkyl radical. For example, such radicals include benzyl, diphenylmethyl, triphenylmethyl, phenylmethyl and diphenylethyl. The terms benzyl and phenylmethyl are interchangeable. The term "heteroaralkyl" includes heteroaryl-substituted alkyl radicals,
Here, the heteroaralkyl radical may be substituted by three or more of the above aralkyl radicals. The term “perhaloaralkyl” refers to an aryl-substituted alkyl radical in which an aralkyl radical may be replaced by three or more of the above halo radicals.

The term “aralkylsulfinyl” includes the aralkyl radicals described above, which bind to a sulfinyl radical. “Aralkylsulfinylalkyl” includes an aralkylsulfinyl radical that is bonded to the above alkyl radical. The term "aralkylsulfonyl" includes the aralkyl radicals described above, which bind to a sulfonyl radical. “Aralkylsulfonylalkyl” includes aralkylsulfonylradicals bonded to the above alkyl radicals.

The term “cycloalkyl” includes radicals having 3 to 15 carbon atoms. More preferred cycloalkyl radicals are "lower cycloalkyl" radicals having three to seven carbon atoms. For example, include radicals such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. The term cycloalkyl includes radicals having 7 to 15 carbon atoms and having 2 to 4 rings. For example, radicals such as norbornyl (ie, bicyclo [2.2.1] heptyl) and adamantyl. The term "cycloalkylalkyl" includes cycloalkyl-substituted alkyl radicals. Preferred cycloalkylalkyl radicals are “lower cycloalkylalkyl” radicals having one to six carbon atoms and a cycloalkyl radical attached to the alkyl radical. For example, such radicals include cyclohexylhexyl. The term "cycloalkenyl" includes radicals having 3 to 10 carbon atoms and having one or more carbon-carbon double bonds. Preferred cycloalkenyl radicals are "lower cycloalkenyl" radicals having three to seven carbons. For example, such a radical
Including cyclobutenyl, cyclopentenyl, cyclohexenyl and cycloheptenyl. The term “halocycloalkyl” refers to any one of the cycloalkyl carbon atoms
One or more include the halo-substituted radical. For example, specifically, monohalocycloalkyl radicals may have any of the bromine, chlorine or fluorine atoms in the radical. The dihalo radical may have any two or more of the same halo atom or a combination of different halo atoms,
A polyhalocycloalkyl radical may have more than two of the same halo atom or a combination of different halo atoms. More preferred halocycloalkyl radicals are "lower halocycloalkyl" radicals having three to about ten carbon atoms. For example, such halocycloalkyl radicals include fluorocyclopropyl, difluorocyclobutyl, trifluorocyclopentyl, and dichlorocyclopropyl. The term "halocycloalkenyl" includes radicals wherein any one or more of the cycloalkenyl carbon atoms is replaced with the above halo. Specifically, it includes monohalocycloalkenyl, dihalocycloalkenyl and polyhalocycloalkenyl radicals.

The term “cycloalkoxy” includes cycloalkyl radicals attached to oxy radicals. For example, such radicals include cyclohexoxy and cyclopentoxy. The term "cycloalkoxyalkyl" also includes radicals in which one or more of the cycloalkoxy radicals is bonded to an alkyl radical to form monocycloalkoxyalkyl and dicycloalkoxyalkyl radicals. For example, such radicals include cyclohexoxyethyl. The term “cycloalkoxy” radical may be substituted on one or more halo atoms such as fluorine, chlorine or bromine to provide “halocycloalkoxy” and “halocycloalkoxyalkyl”.

The term “cycloalkylalkoxy” includes cycloalkyl radicals attached to an alkoxy radical. For example, such radicals include cyclohexylmethoxy and cyclopentylmethoxy. The term "cycloalkenyloxy" includes cycloalkenyl radicals that are bonded to an oxy radical. For example, such radicals include cyclohexenyloxy and cyclopentenyloxy. Alternatively, the term "cycloalkenyloxyalkyl" has one or more cycloalkenyloxy radicals attached to an alkyl radical to form monocycloalkenyloxyalkyl and dicycloalkenyloxyalkyl. For example, such radicals include cyclohexenyloxyethyl. “Cycloalkenyloxy” radicals may be substituted on one or more halo atoms such as fluorine, chlorine or bromine to provide “halocycloalkenyloxy” and “halocycloalkenyloxyalkyl” radicals . The term "cycloalkylenedioxy" radical is
Includes cycloalkylene radicals having at least two oxygen atoms attached to one cycloalkylene group. For example, the “alkylenedioxy” radical is 1,2
-Including dioxycyclohexylene.

The term “cycloalkylsulfinyl” includes the above cycloalkyl radicals attached to a sulfinyl radical. "Cycloalkylsulfinylalkyl" includes cycloalkylsulfinyl radicals bonded to the above alkyl radicals. The term "cycloalkylsulfonyl" includes the above cycloalkyl radicals which bind to a sulfonyl radical. “Cycloalkylsulfonylalkyl” includes cycloalkylsulfonyl radicals bonded to the above alkyl radicals. The term "cycloalkylalkanoyl" includes radicals in which one or more cycloalkyl carbons are replaced by one or more carbonyl radicals as described below. Specifically, it includes monocarbonylcycloalkyl and dicarbonylcycloalkyl. For example, monocarbonylcycloalkyl radicals include cyclohexylcarbonyl, cyclohexylacetyl, and cyclopentylcarbonyl. For example, a dicarbonylcycloalkyl radical includes 1,2-dicarbonylcyclohexane.

The term “alkylthio” includes radicals containing a straight or branched chain of 1 to 10 carbon atoms attached to divalent sulfur. More preferred alkylthio radicals are 1 to
It is a "lower alkylthio" radical having six carbon atoms. For example, "lower alkylthio" mother, methylthio _(CH 3 -S-). An “alkylthio” radical may be substituted on one or more halo atoms such as fluorine, chlorine or bromine to provide a “haloalkylthio” radical. For example, such radicals include fluoromethylthio, chloromethylthio, trifluoromethylthio, dichloromethylthio, trifluoroethylthio, fluoroethylthio, tetrafluoromethylthio, pentafluoroethylthio and fluoropropylthio.

The term “alkylarylamino” includes a straight or branched alkyl radical of 1 to 10 carbon atoms and one aryl radical attached to the amino radical. For example, N-methyl-4-methoxyaniline, N-ethyl-4-methoxyaniline and N-methyl-4-trifluoromethoxyaniline are included. The term alkylamino refers to "monoalkylamino" and "dialkylamino", each containing one or two alkyl radicals attached to an amino radical. The term arylamino refers to "monoarylylamino" and "diarylamino", each containing one or two alkyl radicals attached to an amino radical. For example, such radicals include N-phenylamino and N-naphthylamino. The term "aralkylamino" includes the aralkyl radicals described above, which bind to an amino radical. The term aralkylamino refers to "monoaralkylamino" and "diaaralkylamino", which contain one or two aralkyl radicals, respectively, attached to an amino radical. Further, the term aralkylamino refers to "monoaralkylmonoalkylamino" which includes one aralkyl radical and one alkyl radical attached to an amino radical.

The term “arylsulfinyl” includes radicals including the above aryl radicals attached to a divalent S (O) atom. The term "arylsulfinylalkyl"
An arylsulfinyl radical attached to a linear or branched alkyl radical of 1 to 10 carbon atoms is shown. The term “arylsulfonyl” includes the aryl radicals described above which bind to a sulfonyl radical. "Arylsulfonylalkyl"
Includes an arylsulfonyl radical bonded to the alkyl radical. The term "heteroarylsulfinyl" includes radicals including the above heteroaryl radicals attached to a divalent S (O) atom. The term "heteroarylsulfinylalkyl" denotes a heteroalkylsulfinyl attached to a linear or branched alkyl radical of 1 to 10 carbon atoms. The term "heteroarylsulfonyl" includes the above heteroaryl radicals linked to a sulfonyl radical. "Heteroarylsulfonylalkyl" includes a heteroarylsulfonylradical linked to the above alkyl radical.

The term “aryloxy” includes the above aryl radicals bonded to an oxygen atom. For example, such radicals are phenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 3-trifluoromethoxyphenoxy, 4-methylphenoxy, 3-trifluoromethoxyphenoxy, 3-triphenyl Fluoromethylphenoxy, 4-fluorophenoxy, 3,4-dimethylphenoxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 4-fluoro-3-methylphenoxy, 5,6,7,8 -Tetrahydronaphthyloxy, 3-isopropylphenoxy, 3-cyclopropylphenoxy, 3
-Ethylphenoxy, 3-pentafluoroethylphenoxy, 3- (1,1,2
, 2-tetrafluoroethoxy) -phenoxy and 4-tert-butylphenoxy.

The term “aroyl” includes the above aryl radical linked to the above carbonyl radical. For example, such radicals include benzoyl and toluoyl. The term "aralkanoyl" includes the aralkyl radical attached to the carbonyl radical. For example, such radicals include phenylacetyl. The term "aralkoxy" includes oxy-containing aralkyl radicals attached to another radical via an oxygen atom. More preferred aralkoxy radicals include "lower aralkoxy" radicals having a phenyl radical attached to the lower alkoxy radical. For example, such radicals include benzyloxy, 1-phenylethoxy, 3-trifluoromethoxybenzyloxy, 4-propylbenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy and 2-phenylethoxy.

The term “aryloxyalkyl” includes the above aryloxyalkyl attached to an alkyl group. For example, such radicals include phenoxymethyl. The term "haloaryloxyalkyl" includes the above aryloxyalkyl radicals wherein one to five halo radicals are attached to an aryloxy group. The term "heteroaroyl" includes the above heteroaryl radicals to which the above carbonyl radicals are attached. For example, such radicals include furoyl and nicotinyl. The term "heteroaralkanoyl" includes the above heteroaralkyl radical bonded to the above carbonyl radical. For example, such radicals include pyridylacetyl and furylbutyryl. The term "heteroaralkoxy" includes oxy-containing heteroaralkyl radicals bonded to other radicals via an oxygen atom. More preferably, the heteroaralkoxy radical is a "lower heteroaralkoxy" radical having a heteroaryl radical attached to the lower alkoxy radical. The term "haloheteroaryloxyalkyl" means that one to four halo radicals are
Includes the above heteroaryloxyalkyl radicals attached to a heteroaryloxy group.

The term “heteroarylamino” includes the above heterocyclyl radicals attached to an amino group. For example, such radicals include pyridylamino. The term "heteroarylaminoalkyl" includes the above heteroarylamino radicals attached to an alkyl group. For example, such radicals include pyridylmethylamino. The term "heteroaryloxy" includes the above heterocyclyl radicals attached to an oxy group. For example, such radicals are 2-thiophenyloxy, 2-
Includes pyrimidyloxy, 2-pyridyloxy, 3-pyridyloxy and 4-pyridyloxy. The term "heteroaryloxyalkyl" includes the above heteroaryloxy radicals attached to an alkyl group. For example, such radicals include 2-pyridyloxymethyl, 3-pyridyloxyethyl and 4-pyridyloxymethyl.

The term “arylthio” includes the above aryl radicals bonded to a sulfur atom.
For example, such radicals include phenylthio. The term "arylthioalkyl" includes the above arylthio radicals attached to an alkyl group. For example, such radicals include phenylthiomethyl. The term "alkylthioalkyl" includes the above alkylthio radicals attached to an alkyl group. For example, such radicals include methylthiomethyl. The term "alkoxyalkyl" includes the above alkoxy radicals attached to an alkyl group.

The term “carbonyl” refers to a carboxy radical that shares two of the four covalent bonds with an oxygen atom. The term "carboxy" includes the above hydroxy radical attached to one of the two non-shared bonds of the carbonyl group. The term "carboxamide" includes amino, monoalkylamino, dialkylamino, monocycloalkylamino, alkylcycloalkylamino and dicycloalkylamino radicals attached to one of the two non-covalent bonds of the carbonyl group. The term "carboxamidoalkyl" includes the above carboxamido radical attached to an alkyl group. The term "carboalkyl" includes the above carboxy radicals attached to an alkyl group. The term "carboalkoxy" includes the above alkoxy radical attached to one of the two non-shared bonds of the carbonyl group. The term "carboaralkoxy" includes the above aralkoxy radical attached to one of the two non-shared bonds of the carbonyl group. The term "monocarboalkoxyalkyl" includes the above carboalkoxy radical attached to an alkyl group. The term "dicarboalkoxyalkyl" includes two of the above carboalkoxy radicals attached to an alkylene group. The term "monocyanoalkyl" includes one of the above cyano radicals attached to an alkyl group. The term "dicyanoalkylene" includes the two above mentioned cyano radicals attached to an alkyl group. The term "carboalkoxycyanoalkyl" includes one of the above cyano radicals attached to a carboalkoxyalkyl group.

The term “acyl” alone or in combination, for example, hydride, alkyl,
Alkenyl, alkynyl, haloalkylalkoxy, alkoxyalkyl, haloalkoxy, aryl, heterocyclyl, heteroarylalkylsulfinylalkyl, alkylsulfonylalkyl, aralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, alkylthio, arylthio, amino,
A carbonyl or thionocarbonyl group bonded to a radical selected from alkylamino, aralkoxy, arylthio and alkylthioalkyl. For example, "acyl" is formyl, acetyl, benzoyl, trifluoroacetyl, phthaloyl, malonyl, nicotinyl, and the like. The term “haloalkanoyl” includes one or more halo radicals attached to the above alkanoyl radical. For example, such radicals include chloroacetyl, trifluoroacetyl, bromopropanoyl and heptafluorobutanoyl.

[0203] The term "phosphono" includes tetravalent phosphorus bonded to two covalent bonds that bind to an oxygen radical. The term "dialkoxyphosphono" denotes two of the above alkoxy radicals linked to a phosphorus radical by two covalent bonds. The term "diaralkoxyphosphono" refers to two of the above aralkoxy radicals linked to a phosphorus radical by two covalent bonds. The term "dialkoxyphosphonoalkyl" denotes the above dialkoxyphosphono radical attached to an alkyl radical.

The term “amino” refers to a nitrogen atom that contains two substituents, such as hydride, hydroxy, or alkyl, and has one covalent bond to which a single atom, such as carbon, can be attached. For example, such amino _radicals, -NH _2, -NHCH _3, -NHO
Including H and -NHOCH _3. The term "imino" refers to a nitrogen atom that contains one substituent, such as hydride, hydroxy, or alkyl, and has two covalent bonds that can be attached to a single atom, such as carbon. For example, such an imino radical is = N
_H, including = NCH 3, = NOH, and = NOCH _3. The term "iminocarbonyl" refers to a carbon radical having two of the four linkages that share an imino group. For example, such an iminocarbonyl radical is C = NH, C = N
CH ₃ , including C = NOH and C = NOCH ₃ . The term "amidino" includes a saturated or unsaturated amino group attached to one of two available groups for iminocarbonyl radical. For example, such amidino _radicals, NH 2 -C = NH
_{, NH 2 -C = NCH 3,} NH 2 -C = NOCH 3 , and _CH 3 NH-C = NO
H. The term "guanidino" refers to an amidino group attached to an amino group, wherein the amino group can be attached to a third group. For example, the guanidino radical is NH ₂ —C (
_{NH) -NH-, NH 2 -C (} NCH 3) -NH-, NH 2 -C (NOCH 3)
-NH- and _CH 3 NH-C (NOH) including -NH-.

The term “sulfonium” refers to alkyl, alkenyl, aralkyl or aryl
Shows a positive trivalent sulfur atom substituted by three such carbon base groups. The term "di
"Alkylsulfonium" refers to a sulfonium group substituted by two alkyl groups.
You. For example, such a dialkylsulfonium radical is (CH₃)₂S⁺ -Is included. The term "dialkylsulfoniumalkyl" refers to one of the above alkylene groups.
2 shows a dialkylsulfonium group bonded to two bonds. For example, such a gia
The alkylsulfonium alkyl radical is (CH₃)₂S⁺-CH₂CH₂-
Including. The term "phosphonium" refers to alkyl, alkenyl, aralkyl or aryl
Positive tetravalent phosphorus atoms substituted on four of the carbon base groups as indicated. The term "g
"Lialkylphosphonium" refers to a phosphonium group substituted with three alkyl groups.
Show. For example, such a trialkylphosphonium radical is represented by (CH₃) ₃ P⁺including.

The above “alkyl”, “alkenyl”, “alkynyl”, “alkanoyl”,
"Alkylene", "alkenylene", "hydroxyalkyl", "haloalkyl", "haloalkylene", "haloalkenyl", "alkoxy", "alkenyloxy", "alkenyloxyalkyl", "alkoxyalkyl", "aryl" , “Perhaloaryl”, “haloalkoxy”, “haloalkoxyalkyl”, “haloalkenyloxy”, “haloalkenyloxyalkyl”, “alkylenedioxy”, “haloalkylenedioxy”, “heterocyclyl”, “heterocyclyl” “Aryl”, “hydroxyhaloalkyl”, “alkylsulfonyl”, “haloalkylsulfonyl”, “alkylsulfonylalkyl”, “haloalkylsulfonylalkyl”, “alkylsulfinyl”, “alkylsulfinylalkyl”, “alkylsulfonyl” Ynyl, alkylsulfinylalkyl, haloalkylsulfinylalkyl, aralkyl, heteroaralkyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl "
“Cycloalkyl”, “cycloalkylalkanoyl”, “cycloalkylalkyl”, “cycloalkenyl”, “halocycloalkyl”, “halocycloalkenyl”, “cycloalkylsulfinyl”, “cycloalkylsulfinylalkyl”, “cycloalkyl” “Alkylsulfonyl”, “cycloalkylsulfonylalkyl”, “cycloalkoxy”, “cycloalkoxyalkyl”, “cycloalkylalkoxy”, “cycloalkenyloxy”, “cycloalkenyloxyalkyl”, “cycloalkylenedioxy”, “halo” “Cycloalkoxy”, “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", "aralkoxy", "aryloxyalkyl", "haloaryloxyalkyl", "heteroaroyl", "heteroaralka" Noyl "," heteroaralkoxy "," heteroaralkoxyalkyl "," alkylthio "," arylthioalkyl "," alkoxyalkyl ",
The groups "acyl", "amidino", "guanidino", "dialkylsulfonium" and "dialkylsulfoniumalkyl" may optionally be Aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroaryl Aminoalkyl, heteroaryloxy, heteroaryloxyalkyl, haloalkylthio, alkanoy Oxy, alkoxy, alkoxyalkyl, haloalkoxyalkyl, heteroalkoxy, cycloalkoxy, cycloalkenyloxy,
Cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, Alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heterosulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfinylalkyl, alkylsulfonyl,
Alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamide, alkylaminosulfonyl,
Amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamide, diarylamidosulfonyl, monoalkylmonoarylamidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, Alkanoyl, alkenoyl, aroyl, heteroaroyl, aralcanoyl, heteroaralkanoyl, 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, aryloxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, Non-aqueous substituents such as carboalkoxy, alkoxycarbonyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono and diaralkoxyphosphonoalkyl One or more may be substituted.

The term “spacer” has a covalent bond and a backbone of 1-7 contiguous atoms.
One straight chain portion. The spacer is a monovalent or polyvalent chain of 1 to 7 atoms.
You may have. Monovalent chains have = C (H)-, = C (R^2a)-, -O-,
-S-, -S (O)-, -S (O)₂-, -NH-, -N (R^2a)-, -N =
, -CH (OH)-, -CH (OR^2a)-, = C (OR^2a)-And -C (
O)-, which may be constituted by a radical selected from^2aIs
, Alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl
, Aryloxyalkyl, alkoxyalkyl, alkylthioalkyl, ant
Thioalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl,
Haloalkenyl, haloalkoxyalkyl, perhaloalkyl, heteroali
Alkyl, heteroaryloxyalkyl, heteroarylthioalkyl,
And heteroarylalkenyl. Multivalent chains can be one or two or
Is a straight chain of 3 or 4 or 5 or 6 or 7 atoms, or 1 or 2 having a side chain
It can comprise a straight chain of 2 or 3 or 4 or 5 or 6 atoms. chain
Is lower alkylene, lower alkenyl, -O-, -O-CH₂-, -S-CH₂ -, -CH₂CH₂-, Ethenyl, -CH = CH (OH)-, -OCH₂O-,
-O (CH₂)₂O-, -NHCH₂-, -OCH (R^2a) O-, -O (CH ₂ CHR^2a) O-, -OCF₂O-, -O (CF₂)₂O-, -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 =, -OCH₂-, -SCH₂-, S (O) CH₂-, -CH₂(O)-
, -CH (OH)-, = C (OH)-, CH (OR^2a)-, = C (OR^2a)
-, S (O)₂CH₂− And NR^2aCH₂One of the radicals selected from-
Or more, and many other radicals described above, or known or
May be constituted by a group confirmed by a person. Side chains are amidino, guanidino, di
Alkylsulfonium, trialkylphosphonium, dialkylsulfonium
Lucyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylua
Alkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halosik
Loalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloal
Killsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfo
Nylalkyl, heteroarylamino, N-heteroarylamino-N-alkyl
Ruamino, heteroarylaminoalkyl, heteroaryloxy, heteroaryl
Oxyalkyl, haloalkylthio, alkanoyloxy, alkoxy,
Alkoxyalkyl, haloalkoxyalkyl, heteroaralkoxy, cycloal
Coxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkyl
Alkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, ha
Rocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenylo
Xy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro
B, lower alkylamino, alkylthio, alkylthioalkyl, arylamido
No, aralkylamino, arylthio, arylthioalkyl, heteroararco
Xyalkyl, alkylsulfinyl, alkylsulfinylalkyl, aryl
Rusulfinylalkyl, arylsulfonylalkyl, heteroarylsulf
Ynylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl,
Rukylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkyl
Sulfonylalkyl, alkylsulfonamide, alkylaminosulfonyl,
Midosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl
, Monoarylamidesulfonyl, arylsulfonamide, diarylamide
Sulfonyl, monoalkylmonoarylamidosulfonyl, arylsulfini
, Arylsulfonyl, heteroarylthio, heteroarylsulfinyl,
Heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroa
Royl, aralcanoyl, heteroaralkanoyl, haloalkanoyl, alkyl
, Alkenyl, alkynyl, alkenyloxy, alkenyloxyalkyl, a
Lucylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkenyl
, Lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, halo
Alkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydro
Xiaralkyl, hydroxyalkyl, aminoalkyl, hydroxyheteroara
Alkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, a
Ralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl
Kuryl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl
, Arylalkyl, heteroarylalkyl, arylalkenyl, hetero
Arylalkenyl, carboxyalkyl, carboalkoxy, carboarco
Xy, carboxamide, carboxamidoalkyl, cyano, carbohalal
Coxy, phosphono, phosphonoalkyl, dialalkoxyphosphono and dialal
Substitution such as one or more non-aqueous substituents such as xyphosphonoalkyl
It may contain groups.

The compounds of the present invention can exist in tautomeric, geometric or stereoisomers.
In the present invention, cis- and trans-geometric isomers, E- and Z-geometric isomers, R- and S-enantiomers, diastereomers, d-isomers, 1-isomers, racemic mixtures thereof and other mixtures Are contemplated and are within the scope of the present invention. Pharmaceutically acceptable salts in the form of such tautomers, geometric isomers or stereoisomers are also within the scope of the present invention.

The terms “cis” and “trans” mean that two carbon atoms joined by a double bond are each on the same side of the double bond (“cis”) or on the opposite side of the double bond (“trans” ]) Shows the form of a tautomer having a hydrogen atom.

Some of the described compounds containing an alkenyl group are cis and trans
Or is meant to include both "E" and "Z" geometric isomers. Some of the described compounds containing one or more stereoisomers are meant to include the R, S and mixtures of the R and S forms for each stereocenter present.

Some of the compounds described herein may contain one or more ketone or aldehyde carbonyl groups or a combination thereof alone or as part of a heterocyclic ring system. Such carbonyl groups are part or major of the "keto" form of each aldehyde and ketone group, and one or more "enol"
It can be part or main part of the shape. Compounds of the invention having an aldehyde or ketone carbonyl group are meant to include both "keto" and "enol" tautomers. Some of the compounds described in this invention may contain one or more amidocarbonyl groups or a combination thereof alone or as part of a heterocyclic ring system. Such carbonyl groups can each be present as part or main part of the "keto" form of the amide group, and as part or main part of one or more "enol" forms. Compounds of the present invention having an amidocarbonyl group are meant to include both "keto" and "enol" tautomers. The amide carbonyl group can be both oxo (C = O) and thiono (C = S).

Some of the compounds according to the present invention may contain one or more imine or enamine groups, or a combination thereof. Such groups can be present as a part or main part of the "imine" form and one or more "enamine" forms of each group. The compound of the present invention having an imine or enamine group is represented by "
It is meant to include "imine" and "enamine" tautomers.

The present invention also relates to the treatment and prevention of various conditions of thrombosis, including mainly coronary and cerebrovascular diseases, in a subject having such a disease, in a therapeutically effective amount of a compound of formula (I)
):

Embedded image (I) A compound or a pharmaceutically acceptable salt thereof is administered, which is characterized by treatment and prevention with anticoagulant treatment.

In a further aspect, the compounds of the invention of formula (I) or a pharmaceutically acceptable salt thereof described above are administered to a subject with such a disease in a therapeutically effective amount of a compound of formula (I). It is mainly characterized by the treatment and prevention of coronary artery disease, cerebrovascular disease and other coagulation cascade-related diseases, characterized in that the compound represented or a pharmaceutically acceptable salt thereof is administered. Further, the compound of the present invention represented by the formula (I) or a pharmaceutically acceptable salt thereof,
Requirement for inhibition of coagulation of stored whole blood and inhibition of coagulation for testing or storage of other biological samples. Thus, the clotting inhibitors of the present invention include, for example, plasma clotting factors when mammalian blood is contacted with a substance selected from the group consisting of vascular grafts, orthoses, artificial hearts, and extracorporeal circulation. Stored whole blood and all media suspected of containing and where inhibition of coagulation is desired can be added or contacted.

Compounds of formula (I) can inhibit the activity of serine proteases on the coagulation cascade, and thus, in the manufacture of formulations, in mammals, blood, blood products, and mammalian organs, the formation of platelet clots It can be used for methods of prophylactic and therapeutic treatment of diseases mediated by coagulation cascade serine proteases, such as inhibition, inhibition of fibrin formation, inhibition of thrombus formation and inhibition of embolism. In addition, the compound is used for unstable angina, intractable angina, myocardial infarction, transient cerebral ischemic attack, atrial fibrillation, thrombotic attack, embolic attack, deep vein thrombosis, disseminated intravascular coagulation in mammals. It can be used to treat or prevent the onset of disease, the development of fibrin enhancement and the reocclusion or restenosis of revascularized vessels. The compounds can also be used to study the mechanism of action of the coagulation cascade serine protease for the design of better inhibitors and the development of better analytical methods. Also,
The compound represented by the formula (I) can be used for prevention of cerebrovascular disorder (CVA) or stroke.

Further, pharmaceutically acceptable salts of the compounds represented by the formula (I) are included in this group. The term "pharmaceutically acceptable salts" includes the salts commonly used in the form of alkali metal salts and addition salts of free acids or free bases. Natural salts are not important and are not pharmaceutically acceptable. Suitable pharmaceutically acceptable acid addition salts of compounds of formula (I) are
Can be prepared from inorganic or organic acids. For example, inorganic salts are hydrochloric acid, bromic acid, hydrogen iodide, nitric acid, carbonic acid, sulfuric acid and phosphoric acid. Suitable organic acids are aliphatic acids, cycloaliphatic acids, aromatic acids, araliphatic acids, heterocyclic acids, carboxylic acids and sulfonic acids of organic acids, such as formic acid, acetic acid, propionic acid, succinic acid, Glycolic, lactic, malic, tartaric, citric, ascorbic, maleic,
Fumaric acid, pyruvic acid, aspartic acid, glutamic acid, benzoic acid, anthranilic acid, mesylic acid, salicylic acid, p-hydroxybenzoic acid, phenylacetic acid, mandelic acid, embonic (pamoic acid), methanesulfonic acid, ethylsulfonic acid, benzenesulfone It can be selected from acids, sulfanilic acids, stearic acids, cyclohexylaminosulfonic acids, arginic acids, galacturonic acids. formula(
Suitable pharmaceutically acceptable base addition salts of compounds represented by I) are aluminum,
Metal salts made from calcium, lithium, magnesium, potassium, sodium and zinc or organic made from N, N-dibenzylethylenediamine, choline, chloroprocaine, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine Contains salt. All of these salts can be produced from the corresponding compound of the formula (I) by a conventional method, for example, by reacting the compound of the formula (I) with a suitable acid or base.

The present invention also features a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) together with at least one pharmaceutically acceptable carrier, adjuvant or diluent. . The pharmaceutical composition of the present invention comprises one or more non-toxic, pharmaceutically acceptable carriers and / or diluents and / or adjuvants (herein referred to as "carrier" substances) and If desired, the active compound of the formula (I) can be contained together with other active components. Active compounds of the invention are
It can be administered by any suitable route, preferably in the form of a pharmaceutical composition adapted to such a route, and in an effective amount for the intended treatment. For example, the active compounds and compositions can be administered orally, intravascularly, intraperitoneally, subcutaneously, intramuscularly, intraocularly, or topically. For the treatment of the occurrence of fibrin enhancement, the compound
It can be administered intraocularly or topically as well as orally or parenterally. The compounds can be administered in the form of a depot injection or implant preparation which can be formulated in such a manner as to permit a sustained release of the active ingredient. The active ingredient can be compressed into pellets or small cylinders and implanted subcutaneously or intramuscularly as a depot injection or implant. Implants can use inert materials such as biodegradable polymers or synthetic silicones, for example silastic, silicone rubber or other polymer-containing silicones. Also, the compounds can be administered in the form of liposome delivery systems such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. Liposomes can be formed in the form of various phospholipids, such as cholesterol, stearylamine or phosphatidylcholine.

Also, the compounds of the present invention can be delivered by the use of monoclonal antibodies, such as a respective carrier, which is combined with the compound molecules. Also, the compound can be combined with a water-soluble polymer, such as a targeting agent carrier. Such polymers are
Polyvinylpyrrolidone, pyran copolymer, polyhydroxy-propyl-methacrylamide-phenol, polyhydroxyethyl-aspartamide-phenol or polyethylene oxide-polylysine substituted with palmitoyl residues.
Thus, the compounds are useful in achieving biodegradable control of drug release, such as polyacetic acid, polyglycolic acid, copolymers of polyacetic acid and polyglycolic acid, polyepsilon caprolactone, poly Hydroxybutyrate polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates and hydrogels can be combined with crosslinked or amphipathic block copolymers. For oral administration, the pharmaceutical compositions include, for example, tablets, capsules (each containing a sustained or timed release formulation), pills, powders, granules, elixirs, tinctures, suspensions,
It may be in the form of a liquid containing syrup and an emulsion. Preferably, the pharmaceutical compositions are prepared in unit dosage form containing an appropriate amount of the active ingredient. For example, the unit form is a tablet or a capsule. The active ingredient can also be administered by injection as a composition in which, for example, saline, dextranase or water can be used as a suitable carrier.

The amount of the therapeutically active compound to be administered and the dosage of the compound and / or composition of the invention for the treatment of a disease condition will depend on the age, body weight, sex and condition of the subject, the severity of the condition, the severity of the administration. It depends on a variety of factors, including the route and frequency, and especially the compound used, and can therefore be broad. The pharmaceutical composition may range from about 0.1 to 2000 mg, preferably from 0.5 to 30 mg.
The active ingredient can be included in the range of 0 mg. A daily dose of about 0.01-100 mg / kg, preferably about 0.5-20 g / kg, is suitable. Daily administration can be from one to four times daily. The compound is, for example, 0.075 to 30% w / w of the total amount, preferably 0.2 to 2%.
It may be formulated as a topical ointment or cream or suppository with 0% w / w, more preferably 0.4-15% w / w of the active ingredient. For ointment formulations, the active ingredient may be paraffinic or a water-miscible oil base.

As an alternative, the active ingredients can be formulated in oil-in-water cream-based creams. Optionally, the aqueous layer of the cream base is at least 30%
w / w, for example, polyaqueous alcohols such as propylene glycol, butane-1,3-diol, mannitol, glycerol, polyethylene glycol and mixtures thereof. Topical formulations may preferably include compounds that increase the absorption or penetration of the active ingredient into the skin or other affected areas. For example, such dermal penetration enhancers include dimethyl sulfoxide and related analogs. Also, the compounds of the present invention can be formulated by a transdermal method. Preferred topical administration can be accomplished using a patch form of the accumulation and porous membrane or various solid matrices. In each case, the active agent is continually delivered from a storage or microcapsule via a membrane to the active agent-penetrating adhesive and contacts the skin or mucous membrane of the recipient. When the active agent is absorbed into the skin, control and scheduled flow of the active agent is controlled for the recipient. In the case of microcapsules, the encapsulating agent can function as a membrane.

The oil layer of the emulsion of the present invention can be composed of known components by a known method. Between the layers
It consists solely of an emulsifier and may comprise a mixture of at least one emulsifier and a lipid or oil, or both a lipid and an oil. Preferably, both hydrophilic emulsifiers include a lipophilic emulsifier that acts as a stabilizer. It also preferably contains both oils and lipids. Both emulsifiers, with or without stabilizers, constitute emulsifying waxes, which, together with oils and lipids, constitute the emulsifying ointment base which forms the oil dispersion layer of the so-called cream formulation. Emulsifiers and emulsion stabilizers used in the formulations of the present invention include, in particular, Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate and sodium lauryl sulfate. The choice of appropriate oils or lipids for the formulation is based on the desired surface properties to be achieved, and therefore the solubility of the most oil-like active compounds used in pharmaceutical emulsion formulations is very low. Thus, the cream is preferably a non-greasy, non-staining and product that can be washed in suitable concentrations to prevent leakage from tubes or other containers. Diisoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acid, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate, or branched chain ester Linear or branched, single or dibasic alkyl esters, such as mixtures, can be used. These can be used alone or in combinations depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and / or liquid paraffin or other inorganic oils can be used.

For therapeutic purposes, the compounds of the invention will generally have one suitable for the required route of administration.
Combine one or more adjuvants. For oral administration, compounds include 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 and sulfuric acid, gelatin, acacia The gum, sodium alginate, polyvinyl pyrrolidone, and / or polyvinyl alcohol can be mixed and then tableted or encapsulated for convenient formulation. Such capsules or tablets may contain a controlled-release formulation as may provide a dispersion of the active compound in hydroxypropylmethyl cellulose. Formulations for parenteral administration may be in the form of sterile injectable aqueous or non-aqueous solutions or suspensions. These solutions and suspensions can be prepared from sterile powders or granules containing one or more of the above carriers or diluents for use in formulations for oral administration. The compounds 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 modes of administration are well and widely known in the pharmaceutical art.

Indeed, the methods of the present invention for the treatment and prevention of various thrombotic conditions, including coronary and cerebrovascular diseases, the compounds and pharmaceutical compositions of the present invention, alone or in combination with each other or other It is administered in combination with a therapeutic or in vivo diagnostic agent. Further, the coagulation cascade inhibitor of the present invention, for treating or preventing an arterial effect,
Anticoagulants such as, but not limited to, ticlopidine or clopidrogel, for example, fibrinogen receptor antagonists (eg, for treating or preventing unstable angina or restenosis and restenosis after angioplasty), aspirin, Warfarin or heparin, plasminogen activators or thrombolytic agents such as streptokinase which act synergistically in the treatment of various diseases, lipid-lowering agents including anticholesterol agents (eg mevastatin, lovastatin, simvastatin, pravastatin and fluvastatin HMG CoA reductase inhibitors such as HMG C
oA synthetase inhibitors), antidiabetic agents, or other vasoactive agents (loop diuretics, thiazide diuretics, nitrates, aldosterone antagonists (ie,
Spironolactone and epoxy mexylrelenone), angiotensin converting enzyme (eg, ACE) inhibitors, angiotensin II receptor antagonists, beta blockers, antiarrhythmics, antihypertensives and calcium channel inhibitors)
Can be co-administered with a suitable anti-platelet collecting agent. For example, fibrinogen receptor antagonists and the clotting cascade inhibitors of the present invention are useful for patients suffering from coronary artery disease and for patients undergoing angioplasty procedures. Coagulation cascade inhibitors also enhance the activator-mediated thrombolytic agent reperfusion capacity of tissue plasminogen.

The local dosage of a coagulation cascade inhibitor of the present invention and another suitable antiplatelet agent, anticoagulant tax, vasoactive or thrombolytic agent may be an antiplatelet, anticoagulant, vasoactive or A dose similar to the coagulation cascade inhibitor dose without co-administration plus a thrombolytic agent may be provided, substantially depending on the patient in need of treatment, an antiplatelet agent,
The dosage of the coagulation cascade inhibitor without co-administration with an anticoagulant, vasoactive or thrombolytic may be lower. All of the above references are hereby expressly incorporated and incorporated herein.

Although the invention has been described with specific examples, the details of these examples provide an explanation of the invention and do not limit its scope. Without further elaboration, one skilled in the art may, using the above, utilize the full scope of the invention. Accordingly, the following preferred specific embodiments are merely illustrative and are not limiting in any way whatsoever. Compounds containing various types of structural changes described in the schemes or in the examples below are also contemplated. Those skilled in the art will readily understand that known species of the following synthetic conditions and processes are available for the preparation of these compounds. The art can use the preparation methods of the following specific examples, which are characterized by ¹ H NMR
, Mass spectrometry, elemental analysis and similar methods. Also, the compounds may be formed in vivo. The following examples include a detailed description of the preparation of compounds of formula (I). These detailed descriptions are in scope, are merely illustrative, and do not limit the scope of the invention. All parts are by weight and temperatures are in degrees Celsius unless otherwise noted.

The following general synthetic sequence is useful in the present invention. The abbreviations used in the schemes and tables are: “AA” for amino acid, “AcCN” for acetonitrile, “AcOH” for acetic acid, 2,2′-bis (diphenylphosphino) -1,1 "-BINAP" means -binaphthyl, "BnOH" means benzyl alcohol, "BnCHO" means 2-phenylethanal.
"I refer to benzylsulfonyl chloride" BnSO ₂ Cl ", tert-
“Boc” for butyloxycarbonyl, “BOP” for benzotriazol-1-yl-oxy-tris- (dimethylamino), “bu” for butyl, “dba” for dibenzylidene-acetone "DCC" meaning 1,3-dicyclohexylcarbodiimide, "DCM" meaning dichloromethane or methylene chloride, "DIBAH" or "DIBAL" meaning diisobutylaluminum chloride, "DC" meaning dimethylformamide
“MF”, “DMSO” for dimethylsulfoxide, “DPPA” for diphenylphosphorylazide, 1- [3- (dimethylamino) propyl] -3-
“EDC” for ethyl carbodiimide hydrochloride, “Ex. No” for example number, “Fm” for 9-fluorenylmethoxycarbonyl
"oc", "HOBt" for hydroxybenzoltriazole, "LDA" for lithium diisopropylamide, "MW" for molecular weight, "NMN" for N-methylmorpholine, "NMN" for phenyl or aryl P
h "," PHTH "for phthaloyl group," phZ "for 4-nitrobenzyloxy-carbonyl," PTC "for phase transfer catalyst," py "for pyridine, primary organic amine “RNH ₂ ”, “SEM” meaning 2- (trimethylsilyl) ethoxy-methyl chloride, “p-TsOH” meaning paratoluenesulfonic acid, “TBAF” meaning tetrabutylammonium fluoride, 2- ( 1H-benzotriol-1-yl) -1,
"TB" meaning 1,3,3-tetramethyluronium tetrafluoroborate
“TU”, “TEA” for triethylamine, “TFA” for trifluoroacetic acid, “THF” for tetrahydrofuran, “TMS” for trimethylsilyl, “TMSCN” for trimethylsilyl cyanide and benzyloxycarbonyl And “Cbz” or “Z”.

General Synthesis Methods and Detailed Examples The compounds of the present invention can be synthesized, for example, by the following methods and schemes. Various R ² - General synthesis of substituted pyrimidinone, shown in Scheme 1 Scheme 5 below. Substituted benzamidine was obtained by treatment of a solution of ethyl benzimidate hydrochloride in methanol and aminoacetaldehyde dimethyl acetal. Cyclization of benzamidine with dimethylmethoxymethylene-malonate formed a pyrimidinone heterocyclic nucleus with the desired functional group in a further operation. Demethylation of the ester and lithium iodide, followed by Curtius rearrangement of the resulting acid, introduced a critical nitrogen at C-5 as a protected carbamate. N-3 was provided with a glycine moiety by hydrolysis of the dimethyl acetal and oxidation of the resulting aldehyde and sodium chlorate. Protection of the acid as a t-butyl ester, followed by deprotection of the carbamate by hydrogenation gave the free amine at C-5. Treatment of the amine with a sulfonyl chloride or aldehyde under reductive amination conditions gave the sulfonamide or secondary amine, respectively. The protected acid was then unmasked with HCl. These acids were then coupled with various amines under standard peptide coupling conditions. These amines are typically multifunctional and utilize for some protection formation. Removal of the protecting group gave the compound to be evaluated. The synthesis diagram and synthesis method are shown below.

Scheme 1: General Pyrimidinone Synthesis-I

Embedded image

Scheme 2: General pyrimidinone synthesis-I (continued)

Embedded image

Scheme 3: General pyrimidinone synthesis-I (continued)

Embedded image

Scheme 4: General Pyrimidinone Synthesis-I (continued)

Embedded image

Scheme 5: General pyrimidinone synthesis-I (continued)

Embedded image Synthetic FIGS. 1-5 are demonstrated in the following examples.

Example 1

Embedded image

Example 1-A A solution of ethyl benzimidate (92.25 g, 496.9 mmol) (1.68 M) in 300.0 mL dry methanol was cooled to about 0 ° C. and dried methanol (75. (0 mL, 9.0 M), a solution of aminoacetaldehyde dimethyl acetal (73.10 mL, 670.9 mmol) was added dropwise while maintaining the temperature at 5 ° C or lower. The resulting solution was kept at a temperature below 5 ° C. and kept stirring for 3 days, then the reaction mixture was concentrated under reduced pressure to give a yellow oil. Residue is 1N
Dissolved in aOH (750 mL) and extracted with dichloromethane (4 × 250 mL). Combine the organic solutions, dry (MgSO ₄ ), concentrate and add 10% as a yellow oil.
8.13 g of crude N- (2,2-dimethoxyethyl) benzamidine was obtained. Crude N- (2,2-dimethoxyethyl) benzamidine (108.13 g, 519.2 mmol) in dry methanol (125.0 mL, 4.2 M) was partially dimethylmethoxymethylenemalonate (94.13 g, 540.5 mmol) was added at room temperature. The resulting solution was heated to about 100 ° C. and gradually upstream for more than 2 hours. The resulting dark brown solution was cooled to room temperature and diluted with ethyl acetate (1 L).
The organic solution was washed with saturated NH ₄ Cl (2 × 500 mL) and brine (1 × 500 mL).
). The organic solution was dried (MgSO _4), filtered, and concentrated. MPL
The crude product was purified by C (25% ethyl acetate / hexane) and pure methyl- (2,2-dimethoxyethylene-2-phenylpyrimidine-6 (1H) as a tan oil in 73% yield. ^1- H NMR (300 MHz, CDCl ₃ ) δ 8.73 (s, 1H), 7.59-7.49 (m, 5H), 4.86 (t, J =
5.5 Hz, 1H), 4.16 (d, J = 5.4 Hz, 2H), 3.95 (s, 3H), 3.32 (s, 6H); ¹³ C
NMR (75 MHz, CDCl ₃ ) δ 165.9, 164.6, 159.3, 158.2, 134.6, 130.9, 128.93
, 128.78, 114.9, 101.4, 56.0, 55.1, 52.7, 49.1; HRMS (ES) C ₁₆ H ₁₉ N ₂ O ₅ Calculated 319.1294, Found 319.1288.

Example 1B Methyl 1- (2,2-dimethoxyethyl-2-phenylpyrimidin-6 (1H) -one-5-carboxylate (93.00 g, 292) in 420.0 mL of dry pyridine .2 mmol) solution (0.70 M) in a portion of lithium iodide (98.00 mL, 732.2 mmol) at room temperature with stirring.
Was added, at which time an exotherm occurred. The resulting pale brown suspension was heated at reflux for 2 hours. The dark brown reaction was allowed to cool to room temperature and the volatile components were removed under reduced pressure. The resulting oil was diluted with 1N HCl (500 mL). The aqueous solution was extracted with dichloromethane / methanol (4: 1, 4 × 250 mL). The combined organic solution was washed with 6N HCl (2 × 250 mL), dried (MgSO ₄ )
, Filtered and concentrated. The crude product is purified by crystallization (ethyl acetate / hexane) and as a white solid in 63% yield, pure 1- (2,2-dimethoxyethyl-2).
-Phenylpyrimidin-6 (1H) -one-5-carboxylate (Example-1
B) was obtained: ¹ H NMR (300 MHz, CDCl ₃ ) δ 12.99 (s, 1H), 8.97 (s, 1H), 7.63-7.51 (m, 5H
), 4.78 (dd, J = 4.3, 5.5 Hz, 1H), 4.28 (d, J = 5.4 Hz, 2H), 3.30 (s, 6H)
; ¹³ C NMR (75 MHz, CDCl ₃ ) δ 165.8, 165.1, 164.1, 159.1, 133.6, 131.5, 1
29.1, 129.0, 112.6, 101.0, 55.8, 49.2; HRMS (ES) C ₁₅ H ₁₇ N ₂ O ₅ Calculated 305.1
137, found 305.1113.

Example 1C 1- (2,2-Dimethoate) in 800 mL of 1,4-dioxane
Xylethyl-2-phenylpyrimidin-6 (1H) -one-5-carboxylar
(65.93 g, 216.67 mmol) in a suspension (0.27 M).
Cylamine (50.0 mL, 358 mmol) was added, followed by a portion of the diphenylamine.
Ruphosphoryl azide (51.40 mL, 238.5 mmol) was added at room temperature.
. The resulting solution was heated slowly and heated to reflux for 2 hours. Then, the reaction mixture
Benzyl alcohol (45.00 mL, 434.8 mmol) was added to
Reflux was continued for 14 hours. The black solution is allowed to cool to room temperature,
The minute was removed under reduced pressure. The resulting residue was diluted with ethyl acetate (1.5L). Yes
Solution with saturated NH₄Cl (2 × 500 mL), 1N NaOH (1 × 500 mL)
) And saline (1 × 500 ml). Dry the organic solution (MgSO₄ ), Filtered and concentrated to give the crude product. MPLC (15% to 30% ethyl acetate
/ Hexanes), pure [5- [as a light brown solid in 46% yield.
(Benzyloxycarbonyl) amino] -2-phenyl-6-oxo-1,6-
Dihydro-1-pyrimidinyl] acetaldehyde dimethyl acetal (Example 1
C) got:¹ H NMR (400 MHz, CDCl_Three) δ 8.72 (br s, 1H), 7.53-7.32 (m, 11H), 5.20 (s,
 2H), 4.68 (t, J = 5.6 Hz, 1H), 4.12 (d, J = 5.6 Hz, 2H), 3.22 (s, 6H); ¹³ C NMR (100 MHz, CDCl_Three) δ 158.3, 153.7, 153.2, 135.9, 134.9, 134.7, 13
0.1, 129.1, 128.9, 128.8, 128.71, 128.66, 128.4, 125.1, 101.3, 67.7, 55.
4, 48.6; HRMS (EI) C_{twenty two}H_{twenty four}N_ThreeO_Five Calculated 410.1716, Found 410.1741.

Example 1D [5-[(benzyloxycarbonyl) amino] -2-phenyl-6-oxo-1,6-dihydro-1 in 103.0 mL tetrahydrofuran
-Pyrimidinyl] acetaldehyde dimethyl acetal (17.24 g, 42.
35.0 mL of 1 N HCl was added to the 11 mmol) solution. The resulting biphasic mixture was heated to reflux for 12 hours. The reaction mixture was allowed to cool to room temperature and the volatile components were removed under reduced pressure. Resulting residue was diluted with water (200 mL), pH was set to 7 by addition of solid NaHCO _3. The resulting emulsion was extracted with dichloromethane (4 × 150 mL). The mixed organic solution is mixed with water (1 × 200 mL)
), Dried (MgSO ₄ ), filtered and concentrated to give 15.75 g of crude [5
-[(Benzyloxycarbonyl) amino] -2-phenyl-6-oxo-1,6
[Dihydro-1-pyrimidinyl] acetaldehyde was obtained. The crude [5-[(benzyloxycarbonyl) amino] -2-phenyl- in 198.0 mL of tetrahydrofuran, t-butyl alcohol and 2-methyl-2-butane (1: 1: 1.3, 0.21 M). 6-oxo-1,6-dihydro-1-pyrimidinyl] acetaldehyde (15.30 g, 42.11 mmol) solution
Cooled to 0 ° C. The solution was then slowly added to sodium chlorate (29.94 g, 331.1) in 102.0 mL of water (3.2 M based on sodium chlorate).
mmol) and dihydrogen phosphate (35.42 g, 256.7 mmol)
l) The solution was added. The resulting golden biphasic solution was stirred for 10 minutes and the cold bath was removed. The reaction was stirred at room temperature for 1 hour. Volatile components were removed under reduced pressure. The resulting solution was diluted with water (200 mL) and brought to pH 3 by addition of NaHCO ₃ and 1 N hydrochloric acid. The aqueous solution is tetrahydrofuran, dichloromethane (
1: 2, 4 × 180 mL). The combined organic solution was dried (Mg
SO _4), filtered and concentrated to a white solid, in 88% yield, [5 - [(benzyloxycarbonyl) amino] -2-phenyl-6-oxo-1,6-dihydro-1 Pyrimidinyl] acetic acid was obtained: ¹ H NMR (300 MHz, d-DMSO) δ 13.34 (br s, 1H), 9.03 (s, 1H), 7.57-7.34 (m
, 10H), 5.23 (s, 2H), 4.56 (s, 2H); ¹³ C NMR (75 MHz, d-DMSO) δ 169.4, 1
58.0, 154.6, 154.3, 137.1, 134.8, 130.9, 129.4, 129.1, 128.78, 128.72, 1
28.50, 125.5, 67.0, 48.8; HRMS (EI) C ₂₀ H ₁₈ N ₃ O ₅ Calculated 380.1246, Observed 3
80.1246.

Example 1E [5-[(benzyloxycarbonyl) amino] -2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl] acetic acid (5.2503 g) in 70.0 mL chloroform , 13.84 mmol) was cooled to about 0 ° C. in an ice bath. Then, the oxalyl chloride (6.
00 mL, 68.78 mmol) was added dropwise using a syringe. After releasing the active gas, a golden homogeneous solution was obtained. After stirring for 5 minutes, the cooling bath was removed and the solution was stirred at room temperature for another 2 hours. Remove the solvent under reduced pressure, transfer to a high vacuum system, 10 minutes,
The remaining solvent was removed. The resulting yellow solid was combined with 70.0 mL of chloroform (
0.2M), and pyridine (1.70 mL, 21.02 mmol) and 2-methyl-2-propanol (3.5 ml, 36.60 mmol) were added. The resulting tan solution was stirred at room temperature for 1 hour, and then heated and stirred for 12 hours. The resulting mixture was cooled to room temperature and diluted with chloroform (300mL). The organic layer was washed with water (1 × 100 mL), saturated NaHCO ₃ (1 × 100 mL), and brine (1 × 100 mL). The organic solution, dried (MgSO _4), filtered, and concentrated. The crude reaction was purified by MPLC (25% ethyl acetate / hexane) to give the product in 49% yield: ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.81 (br s, 1H), 7.57 -7.38 (m, 11H), 5.27 (s, 2H), 4.57 (s, 2H), 1.47 (s, 9H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.4, 158.
0, 153.2, 135.9, 135.0, 134.4, 130.6, 129.1, 128.9, 128.7, 128.5, 128.4,
125.4, 83.4, 67.7, 49.1, 28.2; HRMS (EI) C ₂₄ H ₂₆ N ₃ O ₅ Calculated 436.1872,
Observed 436.1876.

Example-1F [5-Amino-2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl] acetic acid t-butyl ester (1.8647 g, 41.0 mL) in 21.0 mL of methanol .282 mmol) solution (0.2 M) in 211.3 mg
10% Pd / C was added. The resulting mixture was stirred at room temperature under a hydrogen atmosphere (balloon) for about 16 hours. The crude reaction mixture was filtered through a pad of Celite 545 and the solvent was removed under reduced pressure. The crude product was triturated from ethyl ether to give a yield of 99
% Gave the pure product [5-amino-2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl] acetic acid t-butyl ester (Example-1F): ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.41-7.39 (m, 6H), 4.48 (s, 2H), 4.06 (br s,
2H), 1.39 (s, 9H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.8, 158.6, 149.3, 134.
9, 132.9, 130.0, 128.9, 128.5, 127.7, 82.9, 48.7, 28.1; HRMS (EI) C ₁₆ H _{2 0} N ₃ O ₃ Calculated 302.1505, Observed 302.1491.

Example-1G [5-Amino-2-phenyl-6-oxo-1,6-dihydro-] in 5.5 mL tetrahydrofuran and 2.0 mL dimethylformamide
1-Pyrimidinyl] acetic acid t-butyl ester (1.0300 g, 3.418 mmol
l) Add a portion of N-methylmorpholine (1.20 mL, 10
. 91 mmol) was added. The solution was cooled to 0 ° C. in an ice bath. After stirring for 10 minutes, 5.
To 58.2 mg of a-toluenesulfonyl chloride (3.767 mmol) in 5 mL of tetrahydrofuran (0.68 M) was added dropwise over 5 minutes. The reaction mixture was stirred at 0 ° C. for 2 hours. The reaction mixture was diluted with ethyl acetate (150mL). The organic solution was diluted with 1 N HCl (2 × 25 mL), saturated NaHCO ₃ (2 × 25 mL).
mL) and brine (1 × 50 mL). The organic solution is dried (MgS
O ₄ ), filtered and concentrated under reduced pressure. The resulting yellow solid was triturated from ethyl date, filtered and dried under reduced pressure to give the pure product (Example-1G) as a white solid in 74% yield: ¹ H NMR ( 400 MHz, d-DMSO) δ 9.34 (s, 1H), 7.76 (s, 1H), 7.55-7.28 (m, 10
H), 4.59 (s, 2H), 4.49 (s, 2H), 1.32 (s, 9H); ¹³ C NMR (100 MHz, d-DMSO)
δ 167.0, 158.8, 156.5, 142.1, 134.5, 131.7, 131.0, 130.1, 129.4, 129.0,
128.94, 128.58, 124.8, 83.0, 59.6, 49.2, 28.1; HRMS (EI) C ₂₃ H ₂₆ N ₃ O ₅ S Calculated 456.1593, Observed 456.1597.

Example 1H 9.0 mL in dioxane, 4M HCl in Example 1G (1.0343)
g, 2.336 mmol) was stirred at room temperature for 12 hours. The crude reaction was concentrated under reduced pressure. The resulting residue was triturated with ethyl ether to give a pure (Example-1H) as a white solid in 87% yield: ¹ H NMR (400 MHz, d-DMSO) δ 9.32 ( s, 1H), 7.74 (s, 1H), 7.51-7.30 (m, 10
H), 4.58 (s, 2H), 4.48 (s, 2H); ¹³ C NMR (100 MHz, d-DMSO) δ 169.2, 158.
7, 156.6, 141.9, 134.5, 131.7, 131.0, 130.1, 129.4, 129.0, 128.90, 128.5
6, 124.8, 59.6, 48.9; HRMS (EI) C ₁₉ H ₁₈ N ₃ O ₅ S Calculated 400.0967, Observed 400
.0959.

Example-1I Acid in 10.0 mL Dimethylformamide (Example-1H)
(406.8 mg, 1.018) in a solution (0.10 M) of N, N-diisopropylethylamine (0.900 mL, 5.167 mmol), N-hydroxybenzotriazole (167.7 mg, 1.241 mmol) and 1 − [3- (
Dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (2
36.1 mg, 1.232 mmol). The resulting mixture was stirred at room temperature for 30 minutes after the mixture became homogeneous. Then, 4- (Cbz
-Amidino) benzylamine (324.6 mg, 1.126 mmol) was added at room temperature. The resulting mixture was then stirred for 18 hours. The reaction mixture was diluted with ethyl acetate (50mL). The organic solution was washed with 5% citric acid (1 × 25 mL), saturated NaHCO ₃ (1 × 25 mL) and brine (1 × 25 mL). The organic solution, dried (MgSO _4), filtered, and concentrated. The crude reaction mixture was triturated with ethyl ether to give the pure product (Example-11) as a white solid: ¹ H NMR (300 MHz, d-DMSO) δ 9.36-9.18 (br m, 3H) , 8.82-8.78 (m, 1H), 7.9
8 (d, J = 8.3 Hz, 2H), 7.84, (s, 1H), 7.56-7.32 (m, 16H), 5.15 (s, 2H).
4.65 (s, 2H), 4.58 (s, 2H), 4.40 (d, J = 5.4 Hz, 2H); HRMS (EI) C ₃₅ H ₃₃ N ₆ O ₆ S ₂ Calculated 665.2182, Observed 665.2177. In dioxane (4: 1, 0.1 M), 3.5 mL methanol and 4 M H
To a solution of Cbz-amidine (Example-11) in Cl was added 45.1 mg, 10% Pd / C. The resulting mixture is placed in a hydrogen atmosphere (balloon) at room temperature for about 1 hour.
Stir for 6 hours. The crude reaction mixture was filtered through a pad of Celite 545 and the solvent was removed under reduced pressure. HPLC (0.1% trifluoroacetic acid, gradient, 5% -9
Purification of the crude product by 5% acetonitrile / water) yielded the pure product as a white solid: ¹ H NMR (300 MHz, d-DMSO) δ 9.31-9.28 (m, 4H), 8.88 (br s, 1H), 7.81-7.7
7 (m, 3H), 7.60-7.54 (m, 5H), 7.43-7.37 (m, 7H), 4.65 (s, 2H), 4.58 (s,
2H), 4.42-4.41 (m, 2H); HRMS (EI) C ₂₇ H ₂₇ O ₄ S Calculated 531.1815, Observed 531.
1794.

Example 2

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The title compound was prepared according to the method of Example 1:¹ H NMR (300 MHz, d-DMSO) δ 9.40-9.33 (m, 4H), 8.86 (s, 1H), 7.82 (s, 2H
), 7.72-7.37 (m, 15H), 4.65-4.59 (m, 4H), 4.41-4.40 (m, 2H); HRMS (EI) C ₂₇ H₂₇N₆O_FourS Calculated 531.1815, Observed 531.1794.

Example 3

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Example-3A 7.0 mL of tetrahydrofuran and dichloromethane (1
: 1, 0.3 M) in [5-amino-2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl] acetic acid t-butyl ester (Example-1F) (613.
To a solution of (7 mg, 2.037 mmol) was added 25.0 mL of acetic acid and phenylacetaldehyde (0.475 mL, 4.060 mmol). The solution was cooled to 0 ° C. in an ice bath and a portion of sodium triacetoxyborochloride (1.9131
g, 9.027 mmol). After stirring for 5 minutes, the ice bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The reaction was quenched by the addition of 1 N NaOH (5 mL) and the mixture was stirred for 5 minutes. The reaction mixture was treated with 0.5N NaOH (100
mL). The aqueous solution was extracted with ethyl acetate (3 × 25 mL). The mixed organic solution was mixed with 0.5N NaOH (1 × 25 mL) and saline (1 × 25 m
L). The solution was dried (MgSO ₄ ), filtered and concentrated under reduced pressure. M
Purification by PLC (25% ethyl acetate / hexane) yielded 7 as a yellow oil.
Example 3A was obtained at 4%: ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.43-7.40 (m, 4H), 7.31-7.26 (m, 2H), 7.23-7.
16 (m, 5H), 4.70 (br s, 1H), 4.49 (s, 2H), 3.38-3.34 (m, 2H), 2.96-2.92
(m, 2H), 1.40 (s, 9H); HRMS (EI) C ₂₄ H ₂₈ N ₃ O ₃ Calculated 406.2131, Observed 406-
2125.

Example 3A (521.3 m) in 13.0 mL of 4N HCl in dioxane
g, 1.286 mmol) solution (0.1 M) was stirred at room temperature for 12 hours. The crude reaction was concentrated under reduced pressure. The resulting residue was triturated with ethyl ether to give the pure product Example-3B in quantitative yield as a yellow solid: ¹ H NMR (300 MHz, d-DMSO) δ 7.66- 7.57 (m, 5H), 7.33-7.23 (m, 6H), 4.57 (
s, 2H), 3.44-3.35 (m, 2H), 2.97-2.92 (m, 2H); ¹³ C NMR (75 MHz, d-DMSO)
δ 168.8, 157.0, 148.0, 139.9, 135.0, 132.2, 129.69, 129.48, 129.07, 126
.9, 48.8, 44.5, 34.5; HRMS (EI) C ₂₀ H ₂₀ N ₃ O ₃ Calculated 350.1505, Observed 350.
1520. Example 3B (497.8 mg, 13.0 mL) in 13.0 mL dimethylformamide.
. 290 mmol) solution (0.10 M) in N, N-diisopropylethylamine (1.800 mL, 10.33 mmol), N-hydroxybenzotriazole (212.8 mg, 1.575 mmol) and 1- [3- (dimethylamino) Propyl] -3-ethylcarbodiimide hydrochloride (302.5 mg,
1.578 mmol) was added. After the mixture became homogeneous, the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was then added with some 4- (Cbz-amidino)
Benzylamine (410.9 mg, 1.425 mmol) was added at room temperature. The resulting solution was then stirred for 18 hours. The reaction mixture was treated with ethyl acetate (50 mL
). The organic solution was washed with 5% citric acid (1 × 25 mL), saturated NaHCO ₃ (1 × 25 mL) and brine (1 × 25 mL). The organic solution, dried (MgSO _4), filtered, and concentrated. The crude reaction mixture was purified by trituration with ethyl ether to give pure product Example-3C as a white solid: ¹ H NMR (400 MHz, d-DMSO) δ 9.08 (br s, 2 H) , 8.62 (t, J = 5.8 Hz, 1H),
7.90 (d, J = 8.3 Hz, 2H), 7.44-7.15 (m, 17H), 5.35 (t, J = 5.9 Hz, 1H),
5.07 (s, 2H), 4.44 (s, 2H), 4.29 (d, J = 5.4 Hz, 2H), 3.31-3.26 (m, 2H),
2.88-2.85 (m, 2H); HRMS (EI) C ₃₆ H ₃₅ N ₆ O ₄ Calculated 615.2720, Found 615.268
8.

4M H in 4.0 mL of methanol and dioxane (3: 1, 0.1M)
To a solution of Example-3C in Cl was added 53.0 mg, 10% Pd / C. The resulting solution was stirred under a hydrogen atmosphere (balloon) at room temperature for about 16 hours. The crude reaction mixture was filtered through Celite 545 and the solvent was filtered under reduced pressure. The crude product was purified by trituration with ethyl ether to give the pure product as a yellow solid:
^{1 H NMR (300 MHz, d} -DMSO) δ 9.62-9.30 (br m, 5H). 7.88 (br m, 2H), 7.58-
6.86 (br m, 15H), 4.59 (br s, 2H), 4.36 (br s, 2H), 3.38 (br s, 2H), 2.9
1 (br s, 2H); HRMS (EI) C ₂₈ H ₂₉ N ₆ O ₂ Calculated 481.2352, Observed 481.2348.
An aryl, 2-heteroaryl, or pyrimidinone having a 2-hetero atom bonded directly can be synthesized using the following Scheme 6 and Scheme 7. Heteroatoms are typically sulfur, nitrogen, oxygen or other suitable heteroatoms. The use of the general procedure in Scheme 6 for the preparation of specific heteroatom-substituted pyrimidinones is described in Examples 4 and 5.

Scheme 6. Method for producing disubstituted pyrimidinones

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Example 4

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Example 4A 5-Nitro-2,4 (1H, 3) in dimethoxysulfoxide
H) To a solution of pyrimidinedione (0.2 M) was added, with stirring, 1.1 equivalents of potassium carbonate. After stirring for about 10 minutes, 1 equivalent of 2- (
A solution of (trimethylsilyl) ethoxymethyl chloride was added dropwise. The reaction mixture was then heated to 40 ° C. and stirred for 18 hours. Typical water removal, then
Chromatographic purification provided the pure product Example-4A.

Example 4B 5-Nitro-1-SEM-2,4 in dimethyl sulfoxide
To a (1H, 3H) pyrimidinedione (Example-4A) solution (0.2M), 1.1 equivalents of potassium carbonate was added with stirring. After stirring for 10 minutes, 1 equivalent of a methyl bromoacetate solution in dimethyl sulfoxide was added dropwise. The reaction mixture was then heated to 40 ° C. and stirred for 18 hours. Typical water removal followed by chromatographic purification provided the pure product Example-4B.

Example 4C A solution of 5-nitro-1-SEM-3-methoxycarbonylmethyl (Example-4B) 2,4 (1H, 3H) pyrimidinedione in methanol is
Degassed with hydrogen gas. Next, 5% Pd / C was added to the solution, and the mixture was stirred at room temperature under a hydrogen atmosphere for 24 hours. The crude reaction was filtered through a pad of Celite 545 and concentrated under reduced pressure. Purified by column chromatography, pure 5-amino-
1-SEM-3-methoxycarbonylmethyl 2,4 (1H, 3H) pyrimidinedione Example-4C was obtained.

Example-4D Tetrahydrofuran and dichloromethane (1: 1, 0.3
M), 5-amino-1-SEM-3-methoxycarbonylmethyl 2,4 (1H
To a solution of (, 3H) pyrimidinedione (Example-4C) was added a catalytic amount of acetic acid and one equivalent of phenylacetaldehyde. The solution was cooled to 0 ° C. in an ice bath and 1 equivalent of sodium triacetoxyborochloride was added. After stirring for 5 minutes, the ice bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The reaction was quenched by the addition of 1 N NaOH,
The mixture was stirred for 5 minutes. Typical water removal followed by chromatographic purification provided the pure product Example-4D.

(Example-4E) Tetrahydrofuran and methanol (1: 1, 0.2M)
Medium, 1-SEM-3-methoxycarbonylmethyl-5- (2-phenylethyl)
To a solution of amino-2,4- (1H, 3H) pyrimidinedione (Example-4D) was added 1 equivalent of lithium hydroxide in water. After complete reaction, the volatile components were removed under reduced pressure. The remaining aqueous solution was cooled in an ice bath and acidified to pH 1 with 1.0N HCl. Extract with organic solvent and remove solvent under reduced pressure to give pure product Example-4E
I got

(Example-4F) 5 equivalents of a 1-SEM-3-methylenecarboxy-5- (2-phenylethyl) amino-2,4 (1H, 3H) pyrimidinedione dimethylformamide solution (0.1 M) Of N, N-diisopropylethylamine, 1 equivalent of N-hydroxybenzotriazole and 1 equivalent of 1- [3- (dimethylamine) propyl] -3-ethylcarbodiimide hydrochloride. The reaction mixture was stirred for 30 minutes. The reaction mixture was then stirred overnight with treatment with one equivalent of the appropriate amine. Typical water removal followed by chromatographic purification provided the pure product Example-4F.

(Example-4G) A solution of 1-SEM-3-methylenecarbamide-5- (2-phenylethyl) amino-2,4 (1H, 3H) pyrimidinedione (0.3M) in tetrahydrofuran was added with tetrahydrofuran. In it, 2 equivalents of tetrabutylammonium fluoride were added. The resulting solution was refluxed for several hours. Typical water removal followed by chromatographic purification provided the pure product Example-4G.

(Example-4H) Solution of 3-methylenecarboxyamine-5- (2-phenylethyl) amino-2,4 (1H, 3H) pyrimidinedione (Example-4G) in N, N-dimethylaniline (0.3 M), 1 equivalent of phosphorous oxychloride was added. The resulting solution was refluxed for several hours. Typical water removal followed by chromatographic purification provided the pure product Example-4H.

(Example-4I) A solution of 2-chloro-3-methylenecarboxamido-5- (2-phenylethyl) amino-2,4 (1H, 3H) pyrimidinedione (Example-4H) in dioxane (Example-4I) 0.3M) was added with two beams of phenylthiol. The resulting solution was refluxed for several hours. Typical water removal followed by chromatographic purification provided the pure product Example-41. 2-thiophenyl-3-methylenecarboxamido-5- (2-phenylethyl) amino-2,4 (1H, 3H) in methanol and 4M HCl dioxane
) Pyrimidinedione (Example-4I) solution (3: 1, 0.1 M) was degassed with hydrogen gas. Next, 5% Pd / C was added to the resulting solution, and the mixture was stirred at room temperature under a hydrogen atmosphere for 24 hours. The crude product was filtered through a pad of Celite 545 and concentrated under reduced pressure. Purification by column chromatography provided the pure product.

Example 5

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Example-5A 2-Chloro-3-methylenecarboxamido-5- (2-phenylethyl) amino-2,4 (1H, 3H) pyrimidinedione and 1 equivalent of 3- in 1-propanol To a solution of pyridineboronic acid (0.5 M) was added 1.2 equivalents of 2.0 M sodium carbonate followed by 1 mol% of tetrakis (triphenylphosphine) palladium. The reaction mixture was heated to reflux for several hours. After cooling to room temperature, removal of typical water followed by chromatographic purification provided the pure product Example-5A. 2- (3-pyridinyl) -3-methylenecarboxamide-5- (2-phenylethyl) amino-2,4 (1H, 3 in methanol and 4M HCl dioxane
H) A pyrimidinedione (Example-5A) solution (3: 1, 0.1 M) was degassed with hydrogen gas. Then, 5% Pd / C was added and the solution was allowed to stand at room temperature under a hydrogen atmosphere.
Stirred for 24 hours. The crude product was filtered through a pad of Celite 545 and concentrated under reduced pressure. Purification by column chromatography provided the pure product. For example, 2- linking / bonding an organic group to a pyrimidinone ring via a heteroatom
Pyrimidinones having an aryl, 2-heteroaryl or 2-hetero atom directly attached can be prepared using Scheme 7 below. In this reaction scheme, the aryl is introduced by a carbon-carbon bond. Suitable heteroatoms for forming heterolinked arylpyrimidinones include sulfur, nitrogen, oxygen or other suitable heteroatoms. The use of the general procedure in Scheme 7 for the preparation of specific heteroatom-substituted pyrimidinones is described in Examples 6 and 7.

Scheme 7: Alternative Method for Pyrimidinone Synthesis

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Example 6

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Example-6A 2-thiouracil (66.7 g, 520.5 mmol) was
Aqueous sodium hydroxide solution (41.6 g sodium hydroxide in 365 mL water)
Dissolved in. The mixture was treated with methyl iodide (37 mL, 583 mmol) and the resulting reaction mixture was stirred at room temperature for 16 hours. The solution was then acidified with Glasil acetate (30 mL). The white precipitate was collected by suction filtration, washed several times with cold water, and dried to give 74 g of Example-6A as a white crystalline solid in quantitative yield.

Example-6B Example-6A (74.0) in Gracill acetate (2275 mL).
g, 520.5 mmol) solution was cooled to 0 ° C. in an ice bath and treated with Br ₂ . The reaction mixture was warmed to room temperature and stirred for 16 hours. The yellow precipitate that formed was filtered and washed three times with ether. 97.2 g of Example-6B was isolated with a yield of 62%.

Example-6C A mixture of calcium hydride in THF was cooled to 0 ° C. and treated with pure Example-6B followed by pure t-butyl bromoacetate. The reaction mixture was stirred at 0 C for 1 hour. Then, after allowing the mixture to warm to room temperature, the reaction mixture was stirred for 2 hours. The reaction mixture was heated to reflux for 16 hours. After cooling the reaction mixture to room temperature, the mixture was slowly added to a 1 L ice-water slurry. The quenched mixture was extracted with dichloromethane (3 × 500 mL). The organic layers were combined and washed with water and brine. After drying the organic layer over MgSO ₄ and filtering, the volatile compounds were removed under reduced pressure and 28.81 g (90%) as an off-white solid as a mixture of N-alkylate and O-alkylate (9: 1). ) -6C) was obtained. ¹ H NMR (300 MHz, CDCl ₃ ) d 8.07 (s, 1H), 4.75 (s, 2H), 2.57 (s, 3H), 1.47
(s, 9H); ¹³ C NMR (75 MHz, CDCl ₃ ) d 165.1, 162.7, 158.4, 152.5, 108.3, 8
3.7, 46.8, 28.2 (3C), 15.5; HRMS (EI) C ₁₁ H ₁₅ BrN ₂ O ₃ S Calculated 335.0065, Found 335.0077.

Example-6D In a glove box filled with argon, a 12 oz. Fischer-Porter bottle containing a magnetic stir bar was added to Example-6C (5.00 g, 1 g).
5.0 mmol), Pd (OAc) ₂ (168 mg, 0.75 mmol, 5 mo)
le%), rac-BINAP (654 mg, 1.05 mmol, 7 mole%)
) CsCO ₃ (6.84 g, 21.0 mmol) and anhydrous degassed toluene (6
5.0 ml) was added. To this mixture was added isopropylamine (3.00 ml, 35
. 2 mmol) was added. The bottle was capped with a pressure head with a pressure gauge and removed from the clove box. Closed system in oil bath 11
Heated to 8-120 ° C. and then magnetically stirred for 16 hours. A headspace pressure of 〜１０10 psi developed during the reaction. The Fischer-Porter bottle containing the reaction mixture was removed from the oil bath, cooled for 30 minutes, opened with an argon flow system, and sampled with a syringe. LCMS analysis showed 65% starting material remaining and 35% product. Under an argon atmosphere, the pressure head was removed and the reaction mixture was treated with Pd (OAc) ₂ (337 mg, 1.5 mmol, 10 mole%),
rac-BINAP (1.00 g, 1.6 mmol, 11 mole%), CsC
O ₃ (10.0 g, 30.7 mmol) and isopropylamine (6.00 m
1, 70.4 mmol). The bottle was capped with a pressure head and heated again to 118-120 ° C. with magnetic stirring. The sampling process was repeated, and the completion of the reaction was checked by LCMS. The reaction mixture was cooled to room temperature and filtered on a medium frit sintered glass funnel. The solid was washed thoroughly with toluene and discarded. The filtrate is concentrated and subjected to flash column chromatography (Make 230-
Purification with 400 mesh SiO ₂ , 10% ethyl acetate in hexane) gave 3.80 g (81% yield) of (Example-6D) as a tan solid. ¹ H NMR (300 MHz, CDCl ₃ ) d 7.05 (s, 1H), 4.74 (s, 2H), 3.44 (septet, J =
6.3 Hz, 1 H), 2.53 (s, 3H), 1.47 (s, 9H), 1.21 (d, J = 6.3 Hz, 6 H); ¹³ C
NMR (75 MHz, CDCl ₃ ) d 165.7 (s), 158.7 (s), 147.4 (s), 130.5 (s), 123.6
(d), 82.9 (s), 45.9 (t), 44.1 (d), 28.0 (q), 22.1 (q), 14.8 (q); HRMS
_{(ESI) C 14 H 24 N} 3 SO 3 Calculated ^{[M + H] + = 314.1538} , Found 314.1539.

Example-6E In a glove box filled with argon, a 3 oz. Fischer-Porter bottle containing a magnetic stir bar was placed into a 6 oz.
20 mmol), Cu (I) -2-thiophenecarboxylate (1.21 g,
6.37 mmol) and Pd (PPh ₃ ) ₄ (100 mg, 0.86 mmol)
2.7 mole% was added. THF (25 ml) was added, the bottle was capped with a pressure head with a pressure gauge and removed from the clove box. The closed system was heated to 70 ° C. in an oil bath and then magnetically stirred for 16 hours. The reaction mixture was cooled to room temperature, opened and diluted with ether (200 ml). The mixture was filtered on a medium frit sintered glass funnel. Green solid in ether (100ml)
And was disposed of. The filtrate is concentrated and purified by flash column chromatography (make 230-400 mesh SiO ₂ , 10% -30% ethyl acetate in hexane) to give 961 g (78% yield) of a tan foam (78% yield). Example-6E
) Obtained: ¹ H NMR (300 MHz, CDCl ₃ ) d 8.39 (s, 1H), 8.31 (d, J = 8.1 Hz, 1H), 7.86 (
d, J = 7.8 Hz, 1H), 7.64 (t, J = 8.1 Hz, 1 H), 7.15 (bs, 1H), 4.51 (s, 2
H), 3.58 (septet, J = 6.0 Hz, 1 H), 1.46 (s, 9H), 1.27 (d, J = 6.3 Hz,
6 H); HRMS (ESI) C ₁₉ H ₂₅ N ₄ O ₅ [M + H] ⁺ calculated = 389.1815, found 389.1825.

Example-6F Example-6 was placed in a 250 mL round bottom flask containing a magnetic stirring bar.
E (755 mg, 1.9 mmol) and trifluoroacetic acid (30 mL) were added.
Was. The mixture is stirred for 30 minutes under a flowing argon atmosphere and
And concentrated. The residue was triturated with ether (50 mL) and heptane (2 × 50
801 g (95% yield) as a clear yellow glass azeotroping with
Got 6F:¹ H NMR (300 MHz, DMSO-d₆) d 8.34-8.26 (m, 2 H), 7.89 (d, J = 7.8 Hz, 1
 H), 7.76 (t, J = 7.9 Hz, 1 H), 7.20 (s, 1 H), 4.51 (s, 2 H), 3.57 (sept
et, J = 6.6 Hz, 1 H), 1.17 (d, J = 6.6 Hz, 6 H); HRMS (ESI) free base C₁₅H ₁₇ N_FourO_Five [M + H]⁺ Calculated = 333.1223, found 333.1199. Method for preparation from Example-6F by the method described for the CBZ protected precursor
Gave the product:¹ H NMR (300 MHz, CDCl_Three) d 9.34 (bs, 1 H), 8.32 (s, 1 H), 8.14 (d, J = 8.
0 Hz, 1 H), 7.81 (t, J = 7.8 Hz, 2 H), 7.53 (d, J = 7.8 Hz, 2 H), 7.47 (
t, J = 7.8 Hz, 1 H), 7.39-7.25 (m, 5 H), 7.08 (s, 1 H), 7.00 (d, J = 7.8
 Hz, 2 H), 5.12 (s, 2 H), 4.61 (d, J = 7.8 Hz, 1 H), 4.35 (s, 2 H), 4.21
 (m, 1 H), 3.50 (d of septets, 8 lines J = 6.3 Hz, 1 H), 1.22 (d, J = 6.
3 Hz, 6 H);¹³C NMR (75 MHz, CDCl_Three) d 168.5 (s), 167.4 (s), 164.0 (s), 1
58.6 (s), 148.2 (s), 143.8 (s), 142.6 (s), 136.6 (s), 136.2 (s), 135.0 (
d), 133.4 (s), 133.2 (s), 129.9 (d), 128.7 (d), 128.3 (d), 127.8 (d), 12
7.5 (d), 124.4 (d), 124.1 (d), 121.8 (d), 67.4 (t), 49.9 (t), 44.1 (d),
43.2 (t), 22.4 (q); HRMS (ESI) C₃₁H₃₂N₇O₆ [M + H]⁺: Calculated 598.2463, measured
Value 598.2414. For the preparation from Example-6G by the method described for SC-81703.
Thus, a product was obtained.

Example 7

Embedded image

Example-7A The preparation from Example-6D was used, using a similar preparation described for Example-6E except for Cs ₂ CO ₃ . Thus, Example-6D (213 mg, 0.68 mmol), pyridine-3-bronic acid 1,
3-propanediol cyclic ester (166 mg, 1.02 mmol)
And _{Cs 2 CO 3 (771mg, 2.37mmol} ) from flash chromatography (make 230-400 mesh _SiO 2, CHCl ₃ in 2% Me
OH), as a slightly yellow glass, 143 mg of Example-7A (61% yield).
%) Obtained: ¹ H NMR (300 MHz, CDCl ₃ ) d 8.79-8.66 (m, 2 H), 7.90-7.26 (complex m,
3 H), 7.16 (s, 1 H), 4.53 (s, 2 H), 3.57 (septet, J = 6.3 Hz, 1 H), 1.44
(s, 9 H), 1.27 (d, J = 6.3 Hz, 6 H); HRMS (ESI) C ₁₈ H ₂₅ N ₄ O ₃ [M + H] ⁺ calculated = 345.1927, found 345.1928.

Example-7B The preparation from Example-7A (143 mg, 0.41 mmol) using a similar preparation described for Example-6F, yielded 212 mg as a yellow foam ( Example -7B (100% yield) was obtained: ¹ H NMR (300 MHz, CDCl ₃ ) d 8.72-8.64 (m, 2 H), 7.95-7.89 (m, 1 H), 7.
62-7.52 (complex m, 2 H), 7.42-7.37 (m, 1 H), 7.20 (s, 1 H), 4.52 (s
, 2H), 3.57 (septet, J = 6.3 Hz, 1 H), 1.18 (d, J = 6.3 Hz, 6 H); HRMS
_{(ESI) C 14 H 17 N} 4 O 3 [M + H] + calcd 289.1301, found 289.1296.

[0273] (Example -7C) by CBZ preparation from Example -7B to use similar process as described for the protective substance to give Example _{-7C; HRMS (ESI) C 30} H 32 N ₇ O ₄ [M + H] ⁺ calculated = 554.2516, found 554.2523. The product was obtained by the procedure from Example-7C using a similar procedure as described in Example 6.

Example 8

Embedded image According to the method of Example 6, the title compound was _{prepared:. HRMS (ESI) C 24} H 27 N 7 O 2 [M + H] + calcd 446.2304, found 446.2309 pyrimidine methylene analogs of, here, methylene And exists as a substituent to the carbonyl of acetamide at the N-3 position of pyrimidinone, and can be produced using Scheme 8 “General methylene pyrimidinone production method” described in Specific Example 9 below.

Scheme: 8 General methylene pyrimidinone production methods

Embedded image

Example 9

Embedded image

Example 9A [5-[(benzyloxycarbonyl) amino] -2-propyl-6-oxo-1,6-dihydro-1-pyrimidinyl] acetaldehyde solution in tetrahydrofuran and dichloromethane (1: 1) , 0.3 M) solution, a catalytic amount of acetic acid and one equivalent of the appropriate amine were added. The solution was cooled to 0 ° C. in an ice bath,
One equivalent of triacetoxyborochloride was added. After stirring for 5 minutes, the ice bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The reaction was quenched with 1N NaOH and the mixture was stirred for 5 minutes. Typical water removal followed by chromatographic purification provided the pure product Example-9A.

(Example-9B) [5-[(benzyloxycarbonyl) amino] in methanol
] -2-Phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl] acetamide (Example-9A) (0.2 M) was added with 10% Pd / C. The reaction mixture was stirred at room temperature under a hydrogen gas atmosphere (balloon) for about 16 hours. The crude reaction mixture was filtered through a pad of Celite 545 and the solvent was removed under reduced pressure. The residue was triturated with ethyl ether to give pure product Example-9B.

(Example-9C) [5-Amino-2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl] acetamide (Example-9B) solution in tetrahydrofuran and dichloromethane (1: 1, 0.3M), a catalytic amount of acetic acid and one equivalent of phenylacetaldehyde were added. The solution was cooled to 0 ° C. in an ice bath and 1 equivalent of triacetoxyborochloride was added. After stirring for 5 minutes, the ice bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The reaction was quenched by the addition of 1 N NaOH and the mixture was stirred for 5 minutes. Typical water removal followed by chromatographic purification provided the pure product Example-9C. [5- (2-Phenylethyl) amino-2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl] acetamide solution in 4M HCl dioxane (
0.2M) was stirred for several hours. After completion of the reaction, volatile components were removed under reduced pressure.
The residue was triturated with ethyl ether to give pure product 5. Sulfonyl analogs of pyrimidinone, where sulfonyl is the N of pyrimidinone
At position -3, which is present as a substituent for the carbonyl group of acetamide,
In place of dimethoxyethylamine, it can be prepared using a general preparation method based on the method disclosed in Schemes 1-5 by substituting the appropriate aminomethanesulfonamide of the N-Boc-amidino-protected amine. For example, N- (4-amidinobenzyl) 2-aminomethanesulfonamide can be used. Using this method, the sulfone analogs of Examples 10 and 11 can be prepared.

Example 10

Embedded image

Example 11

Embedded image

Triazinone analogs of pyrimidinone, wherein nitrogen is present as a substituent on carbon at the 4-position of pyrimidinone and is described in Scheme 9 below in Specific Example 12 “General 4-azapyrimidinone method of manufacture. ] Can be manufactured. Scheme 9: General 4-azapyrimidinone production method

Embedded image

Example 12

Embedded image

Example-12 A solution of glycine t-butyl ester hydrochloride (1 mmol) in dichloromethane was treated with benzoyl chloride (1 mmol) and triethylamine (2 mmol). The reaction mixture was stirred at room temperature for 16 hours. The mixture was washed with water and extracted with dichloromethane. The combined organic layers are
And dried over MgSO _4. The volatile components were removed under reduced pressure to give pure product Example-1
2A was isolated.

(Example-12B) N-benzoylglycine t-butyl ester (1 mmol)
A mixture of Example-12A), Lawesson's reagent (0.5 mmol) and toluene was heated to 80 ° C. for 16 hours. The reaction mixture was concentrated under reduced pressure. Purification by silica gel column chromatography provided the pure product Example-12B.

Example-12C A mixture of N-thiobenzylglycine t-butyl ester (1 mmol; Example 12B) in dichloromethane at −78 ° C. with trimethyloxonium tetrafluoroborate (1.1 mmol). Processed. After stirring the reaction mixture for 1 hour, the mixture was washed with NaHCO ₃ (aq) and extracted with dichloromethane. The combined organic layers were dried over MgSO _4, and filtered. The volatile organic compounds were concentrated and the desired product Example-12C was isolated.

(Example-12D) A solution of N-thiomethylbenzylglycine t-butyl ester (1 mmol; Example-12C) in methanol was treated with hydrazine (1 mmol).
). Volatiles were removed under reduced pressure and the desired compound Example-12D was isolated without further purification.

Example-12E A mixture of compound Example-12D (1 mmol) and ethylthiooxamate (1 mmol) in methanol was heated to reflux for 4 hours. A precipitate of colorless crystals resulted, and the crystals of the desired product Example-12E were isolated by suction filtration. Compound Example-12E (1 mmol) and pyridine (5 mmol) in acetonitrile
mmol) in acetonitrile in a-toluenesulfonyl chloride (
3 mmol) solution. The reaction mixture was stirred at −10 ° C. to 0 ° C. for 3 hours. A white precipitate formed after the end of the reaction. The crystals of the desired product Example-12F were isolated by suction filtration.

Example-12G Compound of trifluoroacetic acid in anisole with compound Example-12F
(1 mmol) at 0 ° C. The reaction mixture was stirred at 0 C for 1 hour. The reaction mixture was extracted with an organic solvent, and the organic solvent was removed under reduced pressure to obtain a pure product Example-12G.

(Example-12H) Compound Example-12G (1 mmol), EDC (1.3 m
mol) and HOBt (1.3 mmol) in DMF, and the mixture
Stirred at 0 ° C. for 15 minutes. To this mixture was added benzyl-[[(4-z methylmethylphenyl) iminomethyl] amino] carbamate hydrochloride (1.3 mmol) in DMF.
) And DIEA (1.3 mmol) solution. Typical water removal followed by chromatographic purification provided the desired product Example-12H. Compound Example-12H (1 mmol), p-toluenesulfonic acid monohydride (1 mmol) and 10% Pd on activated carbon (0.1 mmol) were mixed with methanol. The mixture was stirred for 2 hours under a nitrogen atmosphere introduced and maintained through a rubber balloon. The crystals were filtered and the methanol was removed to isolate the desired product.

The compounds of formula (I) of the present invention having hydroxy, thiol and amine functions can be converted into various derivatives. Alternatively, a derivative of a compound of formula (I) may be prepared by first converting one or more of the compounds in the process prior to converting the derivatized intermediate to a compound of formula (I). It can be obtained by derivatizing the above intermediate. Hydroxy in alcohol or phenol form can be readily converted to esters of carboxylic, sulfonic, carbamic, phosphonic and phosphoric acids. Acylation to form a carboxylic acid ester is readily effected by use of a suitable acylating agent such as a fatty acid anhydride or fatty acid chloride. Also, the corresponding aryl and heteroaryl anhydrides or acid chlorides can be used. Such a reaction is generally performed using an amine catalyst such as pyridine in an inert solvent. Similarly, carboxylic esters (urethanes) can be obtained by the reaction of isocyanates and carbamoyl chlorides with hydroxy.
Sulfonic, phosphonic and phosphoric esters can be prepared using the corresponding acid chloride and similar reagents. Compounds of formula (I) having at least one thiol group can be converted to the corresponding thioester derivatives analogous to the thioesters of alcohols and phenols using similar reagents and similar reaction conditions. Compounds of formula (I) having a primary or secondary amine group can be converted to the corresponding amide derivatives. Carboxylic acid amides can be prepared using reaction conditions similar to those used for alcohols and phenols, using appropriate acid chlorides or anhydrides. Ureas corresponding to the corresponding primary or secondary amines can be prepared using carbamoyl chloride directly in the presence of an isocyanate and an acid scavenger such as triethylamine or pyridine. Sulfonamides can be prepared from the corresponding sulfonyl chloride in the presence of aqueous sodium hydroxide or a tertiary amine. Means and methods for the preparation of suitable derivatives are described in House's Modern Synthetic.
Reactions, WABenjamin, Inc., Shriner, Fuson, and Curtin, The Systemat
ic Identification of Organic Compaunds, 5th Edition, Jone Wiley & Sons,
and Fieser and Fieser, Reagents for Organic Synthesis, Volume 1, Jone Wi
You can see it on ly & Sons. Various reagents which can be used to derivatize the hydroxy, thiol and amine of the compounds of formula (I) are commercially available or from the above references and are hereby expressly incorporated herein by reference. Incorporate.

The compounds of formula (I) of the present invention having hydroxy, thiol and amine functions can be alkylated to various derivatives. Alternatively, the alkylated compound of formula (I) can be prepared by first converting one of the preparations prior to converting the alkylated intermediate to a compound of formula (I). Alternatively, it can be obtained by alkylating a further intermediate. The hydroxy of the compound of formula (I) can be easily converted to an ether. Alkylation to form ethers is readily effected by the use of a suitable alkylating agent such as an alkyl bromide, alkyl iodide or alkyl sulfide. The corresponding aralkyl, heteroaralkyl, aralkyloxyalkyl and heteroaralkyloxyalkyl bromides, iodides and sulfides can also be used. Such reactions are generally carried out using alkoxide-forming agents such as sodium hydride, potassium t-butoxide, sodium amide, lithium amide and n-butyllithium using DMF, DMSO, TH
It is carried out using an inert solvent such as F and similar analogs, an amine catalyst such as pyridine in an inert solvent. Compounds of formula (I) having at least one thiol group can be converted into the corresponding thioether derivatives analogous to the thioethers of alcohols and phenols with similar reagents and similar reaction conditions. Compounds of the formula (I) having at least one primary, secondary or tertiary amine group can be converted into the corresponding secondary, tertiary or quaternary ammonium derivatives. Quaternary ammonium derivatives can be made using bromides, iodides and sulfides similar to those used for alcohols and phenols. Conditions include the reaction of the amine by warming with a stoichiometric amount of the amine (ie, one equivalent of a tertiary amine, two equivalents of a secondary amine and three equivalents of a primary amine) with an alkylating agent. Primary and secondary amines and 2 and 1 equivalents of quaternary acid scavenger, respectively, are used simultaneously.
Secondary or tertiary amines can be prepared from the corresponding primary or secondary amine. Primary amines can be dialkylated by reductive amination using an aldehyde such as formaldehyde and sodium cyanoborochloride in the presence of glacial acetic acid. Primary amines can be initially monoalkylated with a monoprotected amine with an easily cleavable protecting group such as trifluoroacetyl. Monomethylated amine protected by an alkylating agent such as dimethyl sulfate in the presence of a non-nucleophilic base such as Barton's base (2-tert-butyl-1,1,3,3-tetramethylguanidine) Get. Removal of the protecting group using aqueous potassium hydroxide gives the desired monoalkylated amine. Furthermore, the means and methods for the production of these derivatives are described in House's Mo
dern Synthetic Reactions, WABenjamin, Inc., Shriner, Fuson, and Curtin
, The Systematic Identification of Organic Compaunds, 5th Edition, Jone
Re published by Wiley & Sons, and Fieser and Fieser, John Wiley & Sons
You can find them in agents fr Organic Synthesis. The perfluoroalkyl derivative can be produced by the production method described in Desmarteas in J. Chem. Soc. Chem. Commun. 2241 (1998). Various reagents that can be used to derivatize the hydroxy, thiol and amine of the compounds of formula (I) are commercially available or by the above-cited references, which are expressly incorporated and incorporated herein.

The results of the above process for the preparation of pyrimidinones by derivatization of nucleophilic substituents that can be present on B, R ¹ , R ² and Y ⁰ are tabulated for specific Examples 13-19. It is shown in FIG. The following specific examples merely illustrate various possibilities and should not be considered limiting by those skilled in the art.

[0294]

[Table 1]

Biological Activity Assay TF-VIIa Assay In this assay, 100 μM of recombinant soluble tissue factor and 2 nM of recombinant human factor VIIa were combined with 0.4 mM of the substrate, N-methylsulfonyl-D-phe-g.
ly-arg-p-nitroaniline and inhibitor or buffer (5 mM CaC
l ₂ , 50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1 mM
1% BNA). Final volume 10
At 0 μl, the reaction is measured immediately at 405 nm and the background absorbance is determined. The plate was incubated at room temperature for 60 minutes, at which time the reaction at 405 nm was monitored for release of p-nitroaniline by
The rate of hydrolysis of the substrate is determined. The percent inhibition of TF-VIIa activity is
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 added to an inhibitor or buffer (50 mM Tris-HC).
1, pH 8.0, 100 mM NaCl, 0.1% BNA). In a final volume of 100 μl, the reaction is immediately measured at 405 nm and the background absorbance is determined. The plate was incubated at room temperature for 60 minutes, at which time 405 minutes were observed for the release of p-nitroaniline.
The rate of hydrolysis of the substrate is determined by monitoring the reaction in nm. The percent inhibition of Xa activity is calculated from OD _{405 nm} values from experimental and control samples.

Thrombin analysis [0297] 0.28 nM human thrombin and 0.06 mM HD-phenylalanyl-L-pipecolyl-L-arginine-p-nitroaniline dihydrochloride were added to an inhibitor or buffer (50 mM Tris- HCl, pH 8.0, 100m
M NaCl, 0.1% BNA). In a final volume of 100 μl, the reaction is immediately measured at 405 nm and the background absorbance is determined. The plate is incubated at room temperature for 60 minutes, at which time the rate of substrate hydrolysis is determined by monitoring the reaction at 405 nm for release of p-nitroaniline. The percent inhibition of thrombin activity is calculated from OD _{405 nm} values from experimental and control samples. Trypsin analysis 5 μg / ml trypsin form IX from pig pancreas and 0.375 mM N
-Α-benzoyl-L-arginine-p-nitroanilide (L-BAPNA) with an inhibitor or buffer (50 mM Tris-HCl, pH 8.0, 100 mM
NaCl, 0.1% BNA). In a final volume of 100 μl, the reaction is immediately measured at 405 nm and the background absorbance is determined. The plate is incubated for 60 minutes at room temperature, at which time the rate of substrate hydrolysis is measured by monitoring the reaction at 405 nm for release of p-nitroaniline. The percent inhibition of trypsin activity is calculated from OD _{405 nm} values from experimental and control samples. The recombinant soluble TF comprising amino acids 1-219 of the mature protein sequence is
E. coli and purified using Mono-Q Sepharose FPLC. Recombinant human VIIa was purchased from American Diagnostica, Greenwich CT and had chromogenic substrate N
-Methylsulfonyl-D-phe-gly-arg-p-nitroaniline is Am
Manufactured by erican Peptide Company, Inc., Sunnyvale, CA. Factor Xa is defined as En
From zyme Reseach Laboratories, South Bend IN, thrombin is Calbiochen,
From La Jolla, CA, trypsin and L-BAPNA were purchased from Sigma, St. Louis MO.
Obtained from. Chromosome substrates S-2765 and S-2238 are available from Chromogenix, S
Purchased from wesden. (ΜM) The biological activity of the compounds of Examples 1 to 19 by biological analysis is summarized in Table 2.

[0298]

[Table 2]

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 11/00 A61P 11/00 43/00 111 43/00 111 C07D 239/46 C07D 239/46 253/06 253/06 F 401/04 401/04 // A61K 31/513 A61K 31/513 31/53 31/53 (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR , GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD) , TG), AP (GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM) , AE, AG AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CR, CU, CZ, DE, DK, DM, DZ, EE, ES, FI, GB, GD , GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, US , UZ, VN, YU, ZA, ZW (72) Inventor Ashton-Tee-Ham-the-Second 1501 B, Oak Forest Parkway Court 1501, St. Louis, Missouri, United States 6372 Inventor William・ Newman United States of America 63122 West Monroe, St. Louis, Missouri 212 (72) Inventor Dallin e Jones United States 63201 Johanna Place Drive, Ballwin, Missouri 408 (72) Inventor Melvin El-Rupel United States 63122 Missouri, United States 1904 F-term (Glassie Ridge Road, St. Louis, Oregon) F-term (reference) ZC42 ZC75

Claims (50)

[Claims] 1. The formula: embedded imageWherein B is a compound of the formula:(Wherein; R⁹, R¹⁰, R¹¹, R¹², R¹³, R³², R³³, R³⁴, R³⁵You
And R³⁶Is independently hydride, acetamido, haloacetamide, amidi
, Guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy
, Alkoxy, alkoxyalkyl, haloalkoxyalkyl, hydroxy, a
Mino, alkoxyamino, nitro, lower alkylamino, alkylthio, alk
Luthioalkyl, alkylsulfinyl, alkylsulfonyl, alkylsulfo
Nilalkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl
, Alkylsulfonamide, alkylaminosulfonyl, amidosulfonyl,
Monoalkylamidosulfonyl, dialkylamidosulfonyl, alkanoyl,
Haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl
, Haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, amino
Alkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy,
Consists of ruboxy, carboxamide, carboxamidoalkyl and cyano
A group represented by the formula:⁹, R¹⁰, R¹¹, R¹²And R¹³Is heteroaryl and hetero
A group which may be selected from the group consisting of cyclyl, provided that R⁹, R¹⁰, R¹¹,
R¹²And R¹³Is a substituent for a group other than B; R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵And R³⁶Independently
, Q^bWhere R is¹⁶And R¹⁹More than one at the same time
Q^bIs not, Q^bIs Q^beB is hydride, trialkylsilyl, C2-C8 alkyl, C3-C8 alkyl
From the group consisting of chirenyl, C3-C8 alkynyl and C2-C8 haloalkyl
The group selected, wherein each member of the group B is up to 6 atoms from the site of attachment of B to A.
Any carbon, including³², R³³, R³⁴, R³⁵And R³⁶From
B is a group consisting of C3-C12 cycloalkyl and C4-heterocyclyl, optionally substituted with one or more groups of the group consisting of
Wherein each ring carbon is R³³May be replaced by
Ring carbons other than the ring carbon of the bonding site of B to A may be substituted with oxo.
Provided that no more than one ring carbon is simultaneously substituted with oxo,
The ring carbon and nitrogen adjacent to the carbon at the point of attachment are R⁹Or R¹³Is replaced by
May be, R⁹And two ring carbons or nitrogens from the binding site are R^{1 0} May be substituted with¹³Ring carbon from the bond site adjacent to the
Is nitrogen, R¹²And is 3 atoms away from the binding site; ¹⁰ The ring carbon adjacent to the position is R¹¹May be substituted, three sites from the binding site
Child away, R¹²The ring carbon adjacent to the position is R³³May be replaced by
4 atoms away from the binding site,¹¹And R³³The ring carbon adjacent to the position is R ³⁴ A is a single covalent bond, (W⁷)_rr-(CH (R^Fifteen))_paAnd (CH (R ^Fifteen ))_pa− (W⁷)_rrA group selected from the group consisting of: wherein rr is 0
An integer selected from 0 to 1, pa is an integer selected from 0 to 6, and W⁷Is
, O, S, C (O), (R⁷) NC (O), (R⁷) NC (S) and N (R⁷ A group selected from the group consisting of rr and pa
No more than one can be zero at the same time; R⁷Is a group selected from the group consisting of hydride, hydroxy and alkyl;^FifteenIs composed of hydride, hydroxy, halo, alkyl and haloalkyl.
Is a group selected from the group consisting of NH and NOH; M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, alkyl, alkenyl, cyano, halo, haloalkyl, ha
Lower alkoxy, haloalkylthio, amino, aminoalkyl, alkylamino,
Amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl,
A group selected from the group consisting of alkoxyamino, thiol and alkylthio; R²Is Z⁰-Q; Z⁰Is a single covalent bond, (CR⁴¹R⁴²)_q, Where q is selected from 1-3
(CH (R⁴¹))_g-W⁰-(CH (R⁴²))_p,here
And g and p are independently an integer selected from 0 to 3 and W⁰Is O, S
, C (O), S (O), N (R⁴¹) And ON (R⁴¹Selected from the group consisting of
And (CH (R⁴¹))_e-W²²-(CH (R⁴²))_h Wherein e and h are independently selected from 0 to 1
Integer to be selected, W²²Is CR⁴¹= CR⁴², 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
Linyl, 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
Peridinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl
Nil, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetra
Selected from the group consisting of lahydrofuranyl and 3,4-tetrahydrofuranyl
Group, but Z⁰Is directly attached to the pyrazinone ring; R⁴¹And R⁴²Is independently amidino, hydroxyamino, hydride,
A group selected from the group consisting of hydroxy, amino and alkyl;⁰In which is a group other than a single covalent bond, and a compound represented by the formula (II): (II) (wherein, D¹, D², J¹, J²And K¹Independently represent C, N, O, S and
And covalent bonds, provided that more than one is a covalent bond
Never, D¹, D², J¹, J²And K¹More than one is O
Never, D¹, D², J¹, J²And K¹S is more than one of
But D¹, D², J¹, J²And K¹Is O and S, then D¹ , D², J¹, J²And K¹One must be a single covalent bond, and D¹ , D², J¹, J²And K¹More than four cannot be N, but
, R⁹, R¹⁰, R¹¹, R¹²And R¹³Are each independently a tetravalent carbon
Maintains properties, trivalent nature of nitrogen, divalent nature of sulfur, and divalent nature of oxygen
K is a group selected from the group consisting of:^4aR^4b)_nWherein n is an integer selected from 1-2; R^4aAnd R^4bIs independently halo, hydride, hydroxyalkyl, a
From alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl
A group selected from the group consisting of: E⁰Is that K is (CR^4aR^4b)_nThen E¹And here, E¹Is
Single covalent bond, C (O), C (S), C (O) N (R⁷), (R⁷) NC (O),
S (O)₂, (R⁷) NS (O)₂, And S (O)₂N (R⁷A group consisting of
A group selected from: Y⁰Is represented by the formula (IV): (IV) (where D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from the group consisting of a bond, provided that more than one is a covalent bond
But not K²Is C and D⁵, D⁶, J⁵And J⁶More than one of the O
There is no, D⁵, D⁶, J⁵And J⁶S is more than one of
But not D⁵, D⁶, J⁵And J⁶Is O and S, then D⁵, D⁶ , J⁵And J⁶One must be a covalent bond, and D⁵, D⁶, J⁵And
And J⁶No more than four are N; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Nitro, alkoxyamino, lower alkylamino, alkylthio, alkylsul
Finyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl,
Alkenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, al
Consists of killamino, haloalkoxyalkyl, carboalkoxy and cyano
A group selected from the group; Q^bIs NR²⁰R²¹, Aminoalkylenyl, Q^be, Where Q^beIs
Hydride and N (R²⁶) C (NR²⁵) N (R²³) (R²⁴),and
C (NR²⁵) NR²³R²⁴A group selected from the group consisting of:²⁰You
And R²¹More than one, at the same time, hydroxy, amino, alkylamino or
Or dialkylamino, and R²³And R²⁴One of
Often, at the same time, hydroxy, amino, alkylamino or dialkylamido
It cannot be R; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
De, alkyl, hydroxy, aminoalkylenyl, amino, dialkylamino,
A group selected from the group consisting of alkylamino and hydroxyalkyl; Q^sIs a single covalent bond, (R³⁷R³⁸)_b, Where b is selected from 1-4
And (CH (R¹⁴))_c-W¹-(CH (R^Fifteen))_dOr
A group selected from the group consisting of, wherein c and d are independently selected from 1-3
Integer and W¹Is C (O) N (R¹⁴), (R¹⁴) NC (O), S
(O), S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴) S (O)₂and
N (R¹⁴A group selected from the group consisting of:¹⁴Binds directly to N
If the group is selected from groups other than halo, and (CR³⁷R³⁸)_band
(CH (R¹⁴))_cIs E⁰Binds to R¹⁴Is selected from the group consisting of hydride, halo, alkyl and haloalkyl
Group to be used; R³⁷And R³⁸Is independently hydride, alkyl and haloalkyl
A group selected from the group consisting of: R³⁸Is a group selected from the group consisting of aroyl and heteroaroyl)
An optionally substituted group; Y⁰Is Q^b−Q^ssAnd here, Q^ssIs (CH (R¹⁴)
)_e-W²-(CH (R^Fifteen))_hWherein e and h are independently 1-2
An integer selected from and W²Is CR^4a= CR^4bHowever, (CH (R ¹⁴ ))_eIs E⁰Binds to Y⁰Is Q^b−Q^ssssAnd Q^b−Q^ssssrSelected from the group consisting of
Group, where Q^ssssIs (CH (R³⁸))_r-W⁵And Q^{ss ssr} Is (CH (R³⁸))_r-W⁶, R is an integer selected from 1-2, and
And W⁵And W⁶Is independently 1,4-indenyl, 1,5-indenyl
1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-i
Ndenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3
, 5-Indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzo
Furanyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzo
Furanyl, 3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzo
Furanyl, 3,7-benzofuranyl, 2,4-benzothiophenyl,
Benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl
, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzo
Thiophenyl, 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-indori
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-
In drill, 3,6-in drill, 3,7-in drill, 1,4-isoindori
1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl
2,5-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-quinolini
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-quino
Linyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquino
Linyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquino
Linyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquino
Linyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquino
Linyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolin
Nyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl,
3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7
A group selected from the group consisting of -cinnolinyl and 4,8-cinnolinyl; and
And W⁵And W⁶Other than the binding site of⁵Ring and W⁶Ring carbon and ar
Lido-containing nitrogen is represented by R⁹, R¹⁰, R¹¹And R¹²One of the group consisting of
Or further substituted, provided that Q^bIs each W⁵Of the substituent
Join to the least numbered position, Q^bIs each W⁶Position with the highest number of substituents
And (CH (R³⁸))_rIs E⁰And a pharmaceutically acceptable salt thereof. 2. The formula:Wherein B is a compound of the formula:(Where R³², R³³, R³⁴, R³⁵And R³⁶, Independently, hydride
, Acetamide, haloacetamide, amidino, guanidino, alkylenedioxy
Si, haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino
, Alkoxyamino, haloalkanoyl, nitro, lower alkylamino, alk
Ruthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, f
Teloaryl, heterocyclyl, alkylsulfonamide, amidosulfonyl,
Monoalkylamidosulfonyl, dialkylamidosulfonyl, alkyl, al
Kenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxya
Alkyl, alkylamino, carboalkoxy, carboxy, carboxamide,
Cyano and Q^bB is a hydride, trialkylsilyl, C2-C8 alkyl, C3-C8 alkyl
Cyrenyl, C3-C8 alkenyl, C3-C8 alkynyl and C2-C8 halo
A group selected from the group consisting of alkyl, wherein each member of group B is B to A
Any carbon containing up to 6 atoms from the bonding site of³², R³³, R³⁴,
R³⁵And R³⁶One or more groups from the group consisting of
B is a group consisting of C3-C12 cycloalkyl and C4-heterocyclyl
Wherein each ring carbon is R³³May be substituted with
A ring carbon other than the ring carbon at the bonding site of B may be substituted with oxo;
However, more than one ring carbon is not simultaneously substituted with oxo and the bond
The ring carbon and nitrogen adjacent to the carbon at the position⁹Or R¹³Even if
Well, R⁹A ring carbon or nitrogen adjacent to the position and two atoms away from the bonding site is represented by R¹⁰ May be substituted with¹³Ring carbon adjacent to the position and two atoms away from the binding site
Or nitrogen is R¹²May be substituted with three atoms separated from the binding site
R¹⁰The ring carbon adjacent to the position is R¹¹May be substituted at the binding site
Are three atoms apart and R¹²The ring carbon adjacent to the position is R³³Even if
Often 4 atoms away from the binding site,¹¹And R³³Ring carbon adjacent to position
Is R³⁴May be substituted; R⁹, R¹⁰, R¹¹, R¹²And R¹³Are independently hydride, aceto
Amide, haloacetamide, alkoxyamino, alkanoyl, haloalkanoy
, Amidino, guadinino, alkylenedioxy, haloalkylthio, alkoxy
Si, hydroxy, amino, lower alkylamino, alkylthio, alkylsulf
Ynyl, alkylsulfamide, alkylsulfonyl, amidosulfonyl, mono
Alkylamidosulfonyl, dialkylamidosulfonyl, alkyl, halo, ha
Loalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carbohydrate
Lucoxy, carboxy, carboxyalkyl, carboxamide and cyano
A group selected from the group consisting of: R⁹, R¹⁰, R¹¹, R¹²And R¹³Is heteroaryl and hetero
A group selected from the group consisting of cyclyl, provided that R⁹, R¹⁰, R¹¹, R¹² And R¹³Is a substituent for a group other than B; A is a single covalent bond and ((CH (R^Fifteen))_pa− (W⁷)_rrGroup consisting of
Wherein rr is an integer selected from 0 to 1 and pa is 0 to
An integer selected from 3 and W⁷Are O, S, C (O), (R⁷) NC (O)
, (R⁷) NC (S) and N (R⁷R) a group selected from the group consisting of:⁷Is a group selected from the group consisting of hydride, hydride and alkyl;^FifteenConsists of hydride, hydride, halo, alkyl and haloalkyl
A group selected from the group; M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, alkyl, cyano, halo, haloalkyl, haloalkoxy
, Amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxy
Cyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol and
R selected from the group consisting of:²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond and (CR⁴¹R⁴²)_qWhere q is from 1-2
The selected integer, (CH (R⁴¹))_g-W⁰-(CH (R⁴²))_p,here
, G and p are independently an integer selected from 0 to 3, W⁰Are O, S and
N (R⁴¹And a group selected from the group consisting of (CH (R⁴¹))_e-W^{2 2} -(CH (R⁴²))_hA group selected from the group consisting of: wherein e and h are
An integer independently selected from 0 to 1, W²²Is CR⁴¹= CR⁴², 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-morph
Folinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazini
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-pyrrolidyl
Dinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl
, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrid
Lofuranyl, 2,5-tetrahydrofuranyl and 3,4-tetrahydrofurani
A group selected from the group consisting of⁰Binds directly to the pyrazinone ring
R⁴¹And R⁴²Consists of hydride, hydride and amino independently
A group selected from the group;⁰Is a group other than a single covalent bond,
A group selected from the group consisting of teloaryl, where adjacent to the carbon at the binding site
Carbon is R⁹The other carbon adjacent to the carbon at the binding site may be
R¹³May be substituted with⁹Adjacent to and 2 atoms away from the carbon at the binding site
Carbon is R¹⁰May be substituted with¹³Adjacent to the carbon at the binding site
The carbon two atoms away from the element is R¹²May be substituted with¹⁰and
R¹²The carbon adjacent to both is R¹¹K may be CHR^4aWherein R is a group represented by^4aIs hydride, hydroxya
Alkyl, alkyl, alkoxyalkyl, alkylthioalkyl and haloal
A group selected from the group consisting of kill; E⁰Is a single covalent bond, C (O) N (H), (H) NC (O), (R⁷) NS (
O)₂And S (O)₂N (R⁷Y) a group selected from the group consisting of:⁰Is represented by the formula (IV): (IV) (where D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from the group consisting of a bond, provided that more than one is a covalent bond
But not K²Is C and D⁵, D⁶, J⁵And J⁶More than one of the O
There is no, D⁵, D⁶, J⁵And J⁶S is more than one of
But not D⁵, D⁶, J⁵And J⁶Is O and S, then D⁵, D⁶ , J⁵And J⁶One must be a covalent bond, and D⁵, D⁶, J⁵And
And J⁶Cannot be N, provided that R¹⁶, R¹⁷, R^{1 8} And R¹⁹Are each independently a tetravalent property of carbon, a trivalent property of nitrogen, sulfur
R and the group selected to maintain the divalent nature of oxygen; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl
, Alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, ha
Loalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and shea
A group selected from the group consisting of¹⁶And R¹⁹Is Q^bBut at the same time R¹⁶and
R¹⁹More than one of the Q^bIs not, Q^bIs Q^beA group represented by the formula: Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride and N (R ²⁶ ) C (NR²⁵) N (R²³) (R²⁴), And C (NR²⁵) NR²³ R²⁴A group selected from the group consisting of:²⁰And R²¹More than one of
But simultaneously with hydroxy, amino, alkylamino or dialkylamino
There is no, R²³And R²⁴More than one is simultaneously a hydroxy,
Cannot be amino, alkylamino or dialkylamino; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
, Alkyl, hydroxy, amino, alkylamino and dialkylamino
A group selected from the group consisting of: Q^sIs a single covalent bond, (R³⁷R³⁸)_b, Where b is selected from 1-4
Integer, and (CH (R¹⁴))_c-W¹-(CH (R^Fifteen))_dConsisting of
A group selected from the group wherein c and d are independently selected from 1-3
Integer, and W¹Is C (O) N (R¹⁴), (R¹⁴) NC (O), S (O)
, S (O)₂, S (O)₂N (R¹⁴), N (R¹⁴) S (O)₂And N (R ¹⁴ A group selected from the group consisting of:¹⁴Is directly bonded to N
, A group selected from groups other than halo, and (CR³⁷R³⁸)_bAnd (CH
(R¹⁴))_cIs E⁰Binds to R¹⁴Is selected from the group consisting of hydride, halo, alkyl and haloalkyl
Group to be used; R³⁷And R³⁸Is independently hydride, alkyl and haloalkyl
A group selected from the group consisting of: R³⁸Is a group selected from the group consisting of aroyl and heteroaroyl)
An optionally substituted group; Y⁰Is Q^b−Q^ssAnd here, Q^ssIs (CH (R¹⁴)
)_e-W²-(CH (R^Fifteen))_hWherein e and h are independently 1-2
An integer selected from and W²Is CR^4a= CH, where (CH (R¹⁴ ))_eIs E⁰Or a pharmaceutically acceptable salt thereof. 3. A method according to claim 1, wherein B is hydride, trialkylsilyl, C2-C8 alkyl.
, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl and
And a group selected from the group consisting of C2-C8 haloalkyl, wherein each member of group B is
Is any of the carbons up to 6 atoms from the bond site of B to A³², R^{3 3} , R³⁴, R³⁵And R³⁶Substituted with one or more groups from the group consisting of
R³², R³³, R³⁴, R³⁵And R³⁶But independently, hydride, ace
Toamide, haloacetamide, amidino, guanidino, alkoxy, hydroxy
, Amino, alkoxyamino, lower alkylamino, alkylthio, amido sulf
Honyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, alkyl
, Halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalco
Xy, carboxy, carboxamide, cyano and Q^bSelected from the group consisting of
A is (CH (R^Fifteen))_pa-W⁷Where pa is selected from 1-3
Integer and W⁷Are O, S and N (R⁷A group selected from the group consisting of:
Where R⁷Is a group selected from the group consisting of hydride and alkyl;^FifteenIs composed of hydride, hydroxy, halo, alkyl and haloalkyl.
A group selected from the group^FifteenIs R^FifteenIs W⁷Directly on carbon
Is a group other than hydroxy and halo; M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, alkyl, cyano, halo, haloalkyl, haloalkoxy
, Amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxy
Cyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol and
R selected from the group consisting of:²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond and (CR⁴¹R⁴²)_qA group selected from the group consisting of
Wherein q is an integer selected from 1-2; R⁴¹And R⁴²Independently comprise hydride, hydroxy and amino
A group selected from the group consisting of aryl and heteroaryl, wherein
One carbon adjacent to the carbon at the binding site is R⁹May be substituted with
Other carbons adjacent to the site carbon are R¹³May be substituted with⁹Adjacent to
The carbon two atoms away from the carbon at the bond site is R¹⁰May be replaced by
, R¹³And two carbons apart from the carbon at the binding site are represented by R¹²Replace with
R¹⁰And R¹²Any carbon adjacent to both R¹¹ May be substituted; R⁹, R¹⁰, R¹¹, R¹²And R¹³But independently hydride, aceto
Amide, haloacetamide, alkoxyamino, alkanoyl, haloalkanoy
, Amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy
Si, hydroxy, amino, lower alkylamino, alkylthio, alkylsulf
Ynyl, alkylsulfamide, alkylsulfonyl, amidosulfonyl, mono
Alkylamidosulfonyl, dialkylamidosulfonyl, alkyl, halo, ha
Loalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carbohydrate
Lucoxy, carboxy, carboxyalkyl, carboxamide and cyano
A group selected from the group consisting of: K is CHR^4aThe group shown, where R^4aIs hydride, hydroxyal
Kill, alkyl, alkoxyalkyl, alkylthioalkyl and haloalkyl
A group selected from the group consisting of⁰Is a single covalent bond, C (O) N (H), (H) NC (O), (R⁷) NS (
O)₂And S (O)₂N (R⁷Y) a group selected from the group consisting of:⁰Has the formula (IV): (IV) [wherein, D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from the group consisting of a bond, provided that more than one is a covalent bond
But not K²Is C and D⁵, D⁶, J⁵And J⁶More than one of the O
There is no, D⁵, D⁶, J⁵And J⁶S is more than one of
But not D⁵, D⁶, J⁵And J⁶Is O and S, then D⁵, D⁶ , J⁵And J⁶One must be a covalent bond, and D⁵, D⁶, J⁵And
And J⁶No more than four are N; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl
, Alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, ha
Loalkyl, haloalkoxy, hydroxyalkyl, alkylamino and shea
A group selected from the group consisting of¹⁶And R¹⁹Is Q^bBut at the same time R¹⁶and
R¹⁹More than one of the Q^bIs not, Q^bIs Q^beMay be
; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride and N (R ²⁶ ) C (NR²⁵) N (R²³) (R²⁴) And C (NR²⁵) NR²³R ²⁴ A group selected from the group consisting of:²⁰And R²¹More than one
Are simultaneously hydroxy, amino, alkylamino or dialkylamino
Never, R²³And R²⁴More than one, at the same time, hydroxy,
Cannot be mino, alkylamino or dialkylamino; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
, Alkyl, hydroxy, amino, alkylamino and dialkylamino
A group selected from the group consisting of: Q^sIs a single covalent bond, (R³⁷R³⁸)_bWhere b is selected from 1-3
Integer, and (CH (R¹⁴))_c-W¹-(CH (R^Fifteen))_dConsisting of
A group selected from the group wherein c and d are independently selected from 1-2
Integer, and W¹Is C (O) N (R¹⁴), (R¹⁴) NC (O), S (O)
, S (O)₂, S (O)₂N (R¹⁴), N (¹⁴) S (O)₂, And N (R ¹⁴ A group selected from the group consisting of:¹⁴Is directly bonded to N
, A group other than halo, (CR³⁷R³⁸)_b, And (CH (R¹⁴))_cIs
, E⁰Binds to R¹⁴Is selected from the group consisting of hydride, halo, alkyl and haloalkyl
Group to be used; R³⁷And R³⁸Is independently hydride, alkyl and haloalkyl
A group selected from the group consisting of: R³⁸Is a group which may be selected from the group consisting of aroyl and heteroaroyl
A group represented by the formula: Y⁰But Q^b−Q^ssAnd here, Q^ssIs (CH (R¹⁴)
)_e-W²-(CH (R^Fifteen))_hWherein e and h are independently 1-2
An integer selected from and W²Is CR^4a= CH, where (CH (R¹⁴ ))_eIs E⁰Or a pharmaceutically acceptable salt thereof. 4. A compound of the formula: Wherein B is a group selected from the group consisting of hydride, trialkylsilyl, C2-C4 alkyl, C3-C5 alkylenyl, C3-C4 alkenyl, C3-C4 alkynyl and C2-C4 haloalkyl; May be substituted at any carbon containing up to 3 atoms from the attachment site of B to A with one or more groups from the group consisting of R ³² , R ³³ and R ³⁴ ; R ³² , R ³³ and R ³⁴ are independently hydride, acetamido, haloacetamide, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkylamide Sulfonyl, alkyl, halo, haloalkyl, haloalkoxy Hydroxyalkyl, carboalkoxy, carboxy, groups selected from the group consisting of carboxamide and cyano; A _{^{is, (CH (R 15))}} pa -N (R 7), here, pa is selected from 1-2 And R ⁷ is a group selected from the group consisting of hydride and alkyl; R ¹⁵ is a group selected from the group consisting of hydride, halo, alkyl and haloalkyl; M is N and R ¹ -C R ¹ is selected from the group consisting of hydride, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and haloalkoxy. group is selected from the group consisting of; ^{R 2 is} represented by ^Z 0 -Q That group; Z ⁰ is a group selected from the group consisting of single covalent bond and CH _2; Q is a group selected from the group consisting of aryl and heteroaryl, where
One carbon adjacent to the carbon at the binding site may be substituted with R ⁹ , and the other carbon adjacent to the carbon at the binding site may be substituted with R ¹³ , adjacent to R ⁹ , and carbon away two atoms of the carbon sites, may be substituted in R ^10, adjacent to the R ^13, carbon distant 2 atoms from the binding sites may be substituted with R ^12, R ¹⁰ And the carbon adjacent to both R ¹² may be substituted with R ¹¹ ; R ⁹ , R ¹¹ , and R ¹³ are independently hydride, hydroxy, amino,
Amidino, guanidino, lower alkylamino, alkylthio, alkylsulfonamide, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamide and cyano R ¹⁰ and R ¹¹ are independently hydride, acetamido, haloacetamide, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamide, amidosulfonyl , Monoalkylamidosulfonyl, dialkylamidosulfonyl, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carbo Shiarukiru, amide carbonyl, halo, groups selected from the group consisting of haloalkyl and cyano; ^{Y 0} is formula (IV): embedded image (IV) wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently a group selected from the group consisting of C, N, O, S and a covalent bond, provided that more than one is Being not a covalent bond, K ² is not O, more than one of C, D ⁵ , D ⁶ , J ⁵ and J ⁶ , and K ² is a member of D ⁵ , D ⁶ , J ⁵ and J ⁶ . More than one cannot be S, and if two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and S, one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is It must be a covalent bond and no more than four of D ⁵ , D ⁶ , J ⁵ and J ⁶ can be N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are independently Hydride, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
R ¹⁶ and R ¹⁹ are a group selected from the group consisting of lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; may be a Q ^b, where at the same ^time, more than one of ^{R 16} and ^{R 19,} is not a ^{Q b,} and ^{Q b} may ^{Q be; Q b is,} NR ²⁰ R ^{21, Q be} , Where Q ^be is hydride and C (N
^{R 25) NR} 23 R ²⁴ and ^{N (R 26) C (NR} 25) N (R 23) ( a group selected from the group consisting of ^{R 2 4), where} more than one of ^{R 20} and ^{R 21} is And not simultaneously, hydroxy, and no more than one of R ²³ and R ²⁴ are simultaneously hydroxy; R ²⁰ , R ²¹ , R ²³ , R ²⁴ , R ^25, and R ²⁶ Is a group independently selected from the group consisting of hydride, alkyl and hydroxy; Q ^s is a group selected from the group consisting of a single covalent bond, CH ₂ and CH ₂ CH ₂ ) Or a pharmaceutically acceptable salt thereof. 5. B is ethyl, 2-propenyl, 2-propynyl, propyl
, Isopropyl, trimethylene, tetramethylene, butyl, 2-butenyl, 3-
Butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,
-Methylpropenyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoro
A group selected from the group consisting of olopropyl and 2,2-difluoropropyl,
Here, each member of B is any one including up to 3 atoms from the binding site of B to A.
Is R³², R³³And R³⁴In one or more groups of the group consisting of
May be substituted; R³², R³³And R³⁴But independently, hydride, amidino, guanidino
, Carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy
, Amino, methoxyamino, ethoxyamino, acetamide, trifluoroacetate
Toamide, N-methylamino, dimethylamino, N-ethylamino, methylthio
, Ethylthio, isopropylthio, trifluoromethyl, pentafluoromethyl
, 2,2,2-trifluoroethyl, 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, amidoca
Rubonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and
Wherein A is a single covalent bond, NH and N (CH₃A group selected from the group consisting of: M is N and R¹A group selected from the group consisting of: -C; R¹But hydride, hydroxy, amino, amidino, hydroxyamino,
Nomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl
, Ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Oroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydro
Xyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy
, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro and bromo
A group selected from the group consisting of: R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond and CH₂A group selected from the group consisting of: Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2
-Pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazo
Ryl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl
Ryl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyridyl
Midinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridinyl
A group selected from the group consisting of dazinyl and 1,3,5-triazin-2-yl
Where one carbon adjacent to the carbon at the binding site is R⁹May be replaced by
And the other carbon adjacent to the carbon at the binding site is R¹³May be substituted with ⁹ And two carbons apart from the carbon at the binding site are represented by R¹⁰Is replaced by
May be, R¹³And two carbons away from the carbon at the binding site are represented by R¹² May be substituted with¹⁰And R¹²The carbon adjacent to both is R¹¹To
May be substituted; R⁹, R¹¹, And R¹³But independently, hydride, amidino, guanidino
, Carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy
, Isopropoxy, propoxy, hydroxy, amino, N-methylamino, N,
N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropyl
Luthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Roethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
Tansulfonamide, amidosulfonyl, N-methylamidosulfonyl, N, N
-Dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-
Hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amide
Carbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl
R is a group selected from the group consisting of:¹⁰And R¹²But independently, hydride, amidino, guanidino, carbo
Xy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy
, Ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamido
No, ethoxyamino, acetamide, trifluoroacetamide, aminomethyl
, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,
N-ethylamino, methanesulfonamide, amidosulfonyl, N-methylamido
Dosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-
Droxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydrido
Roxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro,
A group selected from the group consisting of chloro, bromo and cyano; Y⁰But: 1-Q^b-4-Q^s-2-R¹⁶-3-R¹⁷−5-R¹⁸-6-R¹⁹Benze
, 2-Q^b−5-Q^s-6-R¹⁷-4-R¹⁸-2R¹⁹Pyridine, 3-Q^b-6-Q^s-2-R¹⁶−5-R¹⁸-4-R¹⁹Pyridine, 2-Q^b-4-Q^s-3-R¹⁶-6-R¹⁸Pyrazine, 3-Q^b-6-Q^s-2-R¹⁸−5-R¹⁸-4-R¹⁹Pyridazine, 2-Q^b−5-Q^s-6-R¹⁷-4-R¹⁸Pyrimidine, 5-Q^b-2-Q^s-3-R¹⁶-6-R¹⁹Pyrimidine, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Thiophene, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Thiophene, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Franc, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Franc, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Pyrrole, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Pyrrole, 4-Q^b-2-Q^s−5-R¹⁹Imidazole, 2-Q^b-4-Q^s−5-R¹⁷Imidazole, 3-Q^b−5-Q^s-4-R¹⁶Isoxazole, 5-Q^b-3-Q^s-4-R¹⁶Isoxazole, 2-Q^b−5-Q^s-4-R¹⁶Pyrazole, 4-Q^b-2-Q^s−5-R¹⁹Thiazole, and 2-Q^b−5-Q^s-4-R¹⁷A group selected from the group consisting of thiazoles; R¹⁶, R¹⁷, R¹⁸And R¹⁹But independently, hydride, methyl, ethi
Isopropyl, propyl, carboxy, amidino, guanidino, methoxy,
Ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl,
1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N
-Ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl
Tylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethi
Rusulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-tri
Fluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoro
Methoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bro
Mo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamide
Sulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl
The group consisting of 2,2,2-trifluoro-1-hydroxyethyl and cyano
A group selected from: R¹⁶And R¹⁹But Q^bBut at the same time, R¹⁶And R ¹⁹ More than one of the Q^bAnd Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride and C (N
R²⁵) NR²³R²⁴And N (R²⁶) C (NR²⁵) N (R²³) (R^{2 4} A group selected from the group consisting of:²⁰, R²¹, R²³, And R ²⁴ When any two members of the group consisting of are bonded to the same atom,²⁰, R²¹,
R²³, And R²⁴Is not hydroxy, and the Q ^b The group is directly attached to a carbon atom;²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶But independently, hydrangea
Of methyl, ethyl, propyl, butyl, isopropyl and hydroxy
A group selected from the group consisting of^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
The compound according to claim 4, which is: or a pharmaceutically acceptable salt thereof. 6. The formula: embedded image Wherein A is CH ₂ N (CH ₃ ), CH ₂ N (CH ₂ CH ₃ ), CH ₂ CH ₂ N (C
H ₃ ) and a group selected from the group consisting of CH ₂ CH ₂ N (CH ₂ CH ₃ ); M is a group selected from the group consisting of N and R ¹ -C; R ¹ is hydride, hydroxy, Amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy, hydroxymethyl, R ² is a group selected from the group consisting of 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo; , Z ⁰ -Q; Z ⁰ is selected from the group consisting of a covalent bond 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 A group selected from the group consisting of, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl and 1,3,5-triazin-2-yl, adjacent to the carbon at the binding site One of the carbons may be substituted with R ⁹ , the other carbon adjacent to the carbon at the binding site may be substituted with R ¹³ ,
The carbon adjacent to R ⁹ and 2 atoms away from the carbon at the bonding site may be substituted with R ^10, and the carbon adjacent to R ¹³ and 2 atoms away from the carbon at the bonding site may be substituted with R ¹² . And the carbon adjacent to both R ¹⁰ and R ¹² may be replaced by R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are independently hydride, 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, trifluoro Methoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamide, amidosulfonyl, N-methylamidosulfonyl, N, N-
From dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and cyano A group selected from the group consisting of: R ¹⁰ and R ¹² are independently hydride, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino , Methoxyamino, ethoxyamino, acetamide, trifluoroacetamide, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,
N-ethylamino, methanesulfonamide, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1- Hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro,
Chloro, groups selected from the group consisting of bromo and cyano; ^{Y 0 is: 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 -2R 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} - ^{-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 -5-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 group is selected from the group consisting of thiazole; R ^{16, R 17, R 18} and ^{R 19} are independently hydrido, methyl, ethyl, isopropyl Propyl, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N, N-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-hydro Xyethyl, 2-hydroxyethyl, 2,2
, Group are selected from the group consisting of 2-trifluoromethyl-1-hydroxyethyl, and cyano; ^{Q b is, NR 20 R 21, C (} NR 25) NR 23 R 24 and N ^{(R 26)}
A group selected from the group consisting of C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ), provided that
If any two of the group consisting of R ²⁰ , R ²¹ , R ²³ , and R ²⁴ are bonded to the same atom, then more than one of R ²⁰ , R ²¹ , R ²³ , and R ²⁴ is hydroxy. it not, the ^{Q b} group is attached directly to a carbon ^{atom; R 20, R 21, R} 23, R 24, R 25 and ^{R 26} are independently hydrido, methyl, ethyl, propyl, butyl, A group selected from the group consisting of isopropyl and hydroxy; Q ^s is a single covalent bond, a group selected from the group consisting of CH ₂ and CH ₂ CH ₂
] The compound of Claim 4 represented by these, or its pharmaceutically acceptable salt. 7. A is CH ₂ N (CH ₃ ), CH ₂ N (CH ₂ CH ₃ ), C
Group M is selected from the group consisting of N and ^{_{R 1 -C;; H 2 CH}} 2 N (CH 3) and _{CH 2 CH 2 N (CH 2} CH 3) groups selected from the group consisting of ^{R 1} Is selected from the group consisting of hydride, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro and chloro R ² is a group represented by Z ⁰ -Q; Z ⁰ is a group selected from the group consisting of a covalent bond and CH ₂ ; Q is 5-amino-3-amidocarbonylphenyl, 5-amino -2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3 Amidinophenyl, 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-methanesulfonylaminophenyl, 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,
- Amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, group are selected from the group consisting of 2-thienyl and 3-thienyl; is ^{Y 0 : 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 -2R ^{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 group is selected from the group consisting of thiophene,; ^{R 16} and ^{R 19} are independently hydrido, amidino, amino, Aminomethyl, methoxy, methylamino, hydroxy, hydroxy Methyl, fluoro, groups selected from the group consisting of chloro and cyano; ^{R 16} and ^{R 19} may be a ^{Q b,} where at the same ^time, more than one of ^{R 16} and ^{R 19,} in ^{Q b} not that, ^{Q b} is ^{Q be; R 17} and ^{R 18} are, independently, hydride, fluoro, chloro, hydroxy, hydroxymethyl, amino, group is selected from the group consisting of carboxy and cyano; ^{Q b} is , Q ^be , where Q ^be is a hydride and C (NR ²⁵ ) N
A group selected from the group consisting of R ²³ R ²⁴ ; a group wherein R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydride and methyl; a group wherein Q ^s is CH ₂ The compound according to claim 6, which is or a pharmaceutically acceptable salt thereof. 8. The method according to claim 8, wherein 2- [3- [2- [3-aminophenyl] -6-chloro-N-[[
4-iminomethylphenyl] methyl] -5- [N, N-dimethylhydrazino] -4-
Oxo-1 (4H) -pyrimidinyl]] acetamide; 2- [3- [2- [3-aminophenyl] -6-chloro-5- [N-ethyl-N-
Methylhydrazino] -N-[[4-iminomethylphenyl] methyl] -4-oxo-
1 (4H) -pyrimidinyl]] acetamide; 2- [3- [2- [3-aminophenyl] -6-chloro-5- [N, N-diethylhydrazino] -N-[[4-iminomethylphenyl ] Methyl] -4-oxo-1 (4
H) -Pyrimidinyl]] acetamide; 2- [3- [2- [3-aminophenyl] -5- [N- (azetidin-1-yl)
Amino] -6-chloro-N-[[4-iminomethylphenyl] methyl] -4-oxo-1 (4H) -pyrimidinyl]] acetamide; 2- [4- [3- [3-aminophenyl] -N -[[4-Iminomethylphenyl] methyl] -6- [N, N-dimethylhydrazino] -5-oxo-1 (5H) -1,2
, 4-Triazinyl]] acetamide; 2- [4- [3- [3-aminophenyl] -6- [N-ethyl-N-methylhydrazino] -N-[[4-iminomethylphenyl] methyl]- 5-oxo-1 (5H)-
1,2,4-triazinyl]] acetamide; 2- [4- [3- [3-aminophenyl] -6- [N, N-diethylhydrazino]-
N-[[4-Iminomethylphenyl] methyl] -5-oxo-1 (5H) -1,2,2
4- [triazinyl]] acetamide; 2- [4- [3- [3-aminophenyl] -6- [N- (azetidin-1-yl)]
Amino] -N-[[4-iminomethylphenyl] methyl] -5-oxo-1 (5H)
8. A compound selected from the group consisting of -1,2,4-triazinyl]] acetamide.
Or a pharmaceutically acceptable salt thereof. 9. A compound of the formula:Wherein B is a compound of the formula:(Where R³², R³³, R³⁴, R³⁵And R³⁶, Independently, hydride
, Acetamide, haloacetamide, amidino, guanidino, alkoxy, hydr
Roxy, amino, alkoxyamino, lower alkylamino, alkylthio, amino
Dosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl,
Alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carbo
Alkoxy, carboxy, carboxamide, cyano and Q^bFrom the group consisting of
A is a single covalent bond and (CH (R^Fifteen))_pa− (W⁷)_rrSelected from
Where rr is an integer selected from 0 to 1 and pa is selected from 0 to 3.
Integer and W⁷Is (R⁷) NC (O) and N (R⁷)
Selected group; R⁷Is a group selected from the group consisting of hydride, hydroxy and alkyl;^FifteenIs selected from the group consisting of hydride, halo, alkyl and haloalkyl
M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, hydroxy, hydroxyamino, amidino, amino, shea
No, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoal
Kill, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and
A group selected from the group consisting of halo; R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, O, S, NH and CH₂A group selected from the group consisting of
Q is a group selected from the group consisting of aryl and heteroaryl, wherein
One carbon adjacent to the carbon at the binding site is R⁹May be replaced by
Other carbons adjacent to the carbon at the position¹³May be substituted with⁹Adjacent to
, The carbon two atoms away from the carbon at the binding site is R¹⁰May be substituted with ¹³ And two carbons away from the carbon at the binding site are represented by R¹²Has been replaced by
May be R¹⁰And R¹²The carbon adjacent to both is R¹¹Has been replaced by
Or R⁹, R¹¹And R¹³Is independently hydride, hydroxy, amino, a
Midino, guanidino, lower alkylamino, alkylthio, alkylsulfone
Amide, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoa
Rukylamidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloa
Lucoxy, hydroxyalkyl, carboxy, carboxamide and cyano
A group selected from the group consisting of: R¹⁰And R¹²Is independently hydride, acetamide, haloacetamide
Do, amidino, guadino, guanidino, alkyl, alkoxy, hydroxy, a
Mino, alkoxyamino, lower alkylamino, alkylsulfonamide, amino
Dosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl,
Hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carbo
The group consisting of xyalkyl, amidocarbonyl, halo, haloalkyl and cyano
A group selected from the group consisting of: Y⁰Is represented by the formula (IV): (IV) (where D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from the group consisting of a bond, provided that more than one is a covalent bond
But not K²Are C and D⁵, D⁶, J⁵And J⁶O is more than one of
But D⁵, D⁶, J⁵And J⁶No more than one of which is S
, D⁵, D⁶, J⁵And J⁶Is O and S, then D⁵, D⁶, J⁵ And J⁶One must be a covalent bond, and D⁵, D⁶, J⁵And J⁶ No more than four are N; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl
, Alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloa
Selected from the group consisting of lucoxy, hydroxyalkyl, aminoalkyl and cyano
Selected group; R¹⁶And R¹⁹Is Q^bWhere R¹⁶And R¹⁹of
More than one but at the same time Q^bIs not, Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride, and
C (NR²⁵) NR²³R²⁴A group selected from the group consisting of:²⁰You
And R²¹Are not simultaneously hydroxy, and R^{2 3} And R²⁴No more than one are simultaneously hydroxy; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
Q, a group selected from the group consisting of alkyl, and hydroxy;^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
Or a pharmaceutically acceptable salt thereof. 10. B is a compound of the formula:[Wherein, R³², R³³, R³⁴, R³⁵And R³⁶, Independently, hydride
, Amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy,
Propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetoa
Amide, trifluoroacetamide, N-methylamino, dimethylamino, NE
Tylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl
, Pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3
3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetra
Fluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methyl
Amidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1
-Hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-
Hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amide carbonyl
, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, cyano
And Q^bA group selected from the group consisting of: A is a single covalent bond, NH, N (CH₃), N (OH), CH₂, CH₃CH,
CF₃CH, NHC (O), N (CH₃) C (O), C (O) NH, C (O) N
(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂And CF ₃ CHCH₂A group selected from the group consisting of: M is N and R¹A group selected from the group consisting of: -C; R¹But hydride, hydroxy, amino, amidino, hydroxyamino,
Nomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl
, Ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Oroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydro
Xyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy
, 1,1,1,2-tetrafluoroethoxy, fluoro, chloro and bromo
A group selected from the group consisting of: R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, O, S, NH and CH₂A group selected from the group consisting of
Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2
-Pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazo
Ryl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl
Ryl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyridyl
Midinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridinyl
A group selected from the group consisting of dazinyl and 1,3,5-triazin-2-yl
Where one carbon adjacent to the carbon at the binding site is R⁹May be replaced by
And the other carbon adjacent to the carbon at the binding site is R¹³May be substituted with ⁹ And two carbons away from the carbon at the binding site are represented by R¹⁰Has been replaced by
Well, R¹³And two carbons away from the carbon at the binding site are represented by R¹²Put in
May be replaced by R¹⁰And R¹²The carbon adjacent to both is R¹¹Replace with
R⁹, R¹¹And R¹³But independently, hydride, amidino, guanidino,
Carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy,
Isopropoxy, propoxy, hydroxy, amino, N-methylamino, N, N
-Dimethylamino, N-ethylamino, methylthio, ethylthio, isopropyl
Thio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Ethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy
, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, meta
N-sulfonamide, amidosulfonyl, N-methylamidosulfonyl, N, N-
Dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-h
Droxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidoca
Rubonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and
A group selected from the group consisting of:¹⁰And R¹²But independently, hydride, amidino, guanidino, carbo
Xy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy
, Ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamido
No, ethoxyamino, acetamide, trifluoroacetamide, aminomethyl
, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,
N-ethylamino, methanesulfonamide, amidosulfonyl, N-methylamido
Dosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-
Droxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydrido
Roxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro,
A group selected from the group consisting of chloro, bromo and cyano; Y⁰But: 1-Q^b-4-Q^s-2-R¹⁶-3-R¹⁷−5-R¹⁸-6-R¹⁹Benze
, 2-Q^b−5-Q^s-6-R¹⁷-4-R¹⁸-2R¹⁹Pyridine, 3-Q^b-6-Q^s-2-R¹⁶−5-R¹⁸-4-R¹⁹Pyridine, 2-Q^b-4-Q^s-3-R¹⁶-6-R¹⁸Pyrazine, 3-Q^b-6-Q^s-2-R¹⁸−5-R¹⁸-4-R¹⁹Pyridazine, 2-Q^b−5-Q^s-6-R¹⁷-4-R¹⁸Pyrimidine, 5-Q^b-2-Q^s-3-R¹⁶-6-R¹⁹Pyrimidine, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Thiophene, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Thiophene, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Franc, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Franc, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Pyrrole, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Pyrrole, 4-Q^b-2-Q^s−5-R¹⁹Imidazole, 2-Q^b-4-Q^s−5-R¹⁷Imidazole, 3-Q^b−5-Q^s-4-R¹⁶Isoxazole, 5-Q^b-3-Q^s-4-R¹⁶Isoxazole, 2-Q^b−5-Q^s-4-R¹⁶Pyrazole, 4-Q^b-2-Q^s−5-R¹⁹Thiazole, and 2-Q^b−5-Q^s-4-R¹⁷A group selected from the group consisting of thiazoles; R¹⁶, R¹⁷, R¹⁸And R¹⁹But independently, hydride, methyl, ethi
Isopropyl, propyl, carboxy, amidino, guanidino, methoxy,
Ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl,
1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N
-Ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl
Tylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethi
Rusulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-tri
Fluoroethyl, 2,2,2,3,3-pentafluoropropyl, trifluoro
Methoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bro
Mo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamide
Sulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl
The group consisting of 2,2,2-trifluoro-1-hydroxyethyl and cyano
A group selected from: R¹⁶And R¹⁹But Q^bWhere R¹⁶And R¹⁹of
More than one but at the same time Q^bIs not, Q^bIs Q^be; Q^bBut Q^beWherein Q is a group represented by^beIs a hydride, and C (
NR²⁵) R²³R²⁴A group selected from the group consisting of:²³And R ²⁴ No more than one are simultaneously hydroxy; R²³, R²⁴, And R²⁵Are independently hydride, methyl, ethyl and
A group selected from the group consisting of:^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
The compound according to claim 9, or a pharmaceutically acceptable salt thereof. 11. 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-methoxyphenyl, 4-methoxyphenyl,
A group selected from the group consisting of 3-methylphenyl, 4-methylphenyl, phenyl, and 3-trifluoromethylphenyl; wherein A is CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), CH ₂ CH ₂ and _CH 2 groups selected from the group consisting of _CH 2 CH _2; M is a group selected from the group consisting of N and ^{R 1} -C; ^R 1 is hydrido, hydroxy, amino, amidino, hydroxyamino, A group selected from the group consisting of aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro and chloro; R ² is represented by Z ⁰ -Q group; ^{Z 0} is a single covalent bond, O, S, groups selected from the group consisting of NH and CH _2; is Q, 5- Amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl, 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,
-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,
-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 , group are selected from the group consisting of 2-thienyl and 3-thienyl; ^{Y 0 is: 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 -2R 19 ^{pyridine, 3-Q b -6-Q} s -2-R 16 -5-R 18 -4-R 19 pyridine, is selected from ^{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 group consisting of thiophene that group; ^{R 16} and ^{R 19} , Independently, hydride, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, groups selected from the group consisting of chloro and cyano; ^{R 16} and ^{R 19,} a ^{Q b} Provided that more than one of R ¹⁶ and R ¹⁹ are not simultaneously Q ^b , wherein Q ^b is Q ^be ; R ¹⁷ and R ¹⁸ are independently hydride, fluoro, chloro, hydroxy , groups selected hydroxymethyl, amino, carboxy and cyano; ^{Q b is Q bE, here, Q bE} is hydrido, and consists of ^{C (NR 2 5) NR 23} R 24 A group selected from the group consisting of: R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydride and methyl; Q The compound according to claim 10, wherein ^s is a group represented by CH ₂ , or a pharmaceutically acceptable salt thereof. 12. The formula: embedded imageWherein B is a compound of the formula:(Where R³², R³³, R³⁴, R³⁵And R³⁶, Independently, hydride
, Acetamide, haloacetamide, amidino, guanidino, alkoxy, hydr
Roxy, amino, alkoxyamino, lower alkylamino, alkylthio, amino
Dosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl,
Alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carbo
Alkoxy, carboxy, carboxamide, cyano and Q^bFrom the group consisting of
A is a single bond or (CH (R^Fifteen))_pa− (W⁷)_rrFrom the group consisting of
A selected group, wherein rr is an integer selected from 0 to 1, pa is 0 to 3
An integer selected from, and W⁷Is N (R⁷); R⁷Is a group selected from the group consisting of hydride and alkyl;^FifteenIs selected from the group consisting of hydride, halo, alkyl and haloalkyl
M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, hydroxy, hydroxyamino, amidino, amino, shea
No, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoal
Kill, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and
A group selected from the group consisting of halo; R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond; Q is a group selected from the group consisting of aryl and heteroaryl, wherein
One carbon adjacent to the carbon at the binding site is R⁹May be replaced by
Other carbons adjacent to the carbon at the position¹³May be substituted with⁹Adjacent to
, The carbon two atoms away from the carbon at the binding site is R¹⁰May be substituted with ¹³ And two carbons away from the carbon at the binding site are represented by R¹²Has been replaced by
May be R¹⁰And R¹²The carbon adjacent to both is R¹¹Has been replaced by
Or R⁹, R¹¹And R¹³Is independently hydride, hydroxy, amino, a
Midino, guanidino, lower alkylamino, alkylthio, alkoxy, alk
Rusulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamide
Sulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyal
A group selected from the group consisting of kill, carboxy, carboxamide, and cyano
R¹⁰And R¹²Is independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkyl, alkoxy, alkoxyamino, amino
Alkyl, hydroxy, amino, lower alkylamino, alkylsulfonamide
, Amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfo
Nil, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboal
From koxy, carboxy, carboxamide, carboxyalkyl and cyano
A group selected from the group consisting of: Y⁰Is represented by the formula (IV): (IV) (where D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from the group consisting of a bond, provided that more than one is a covalent bond
But not K²Are C and D⁵, D⁶, J⁵And J⁶O is more than one of
But D⁵, D⁶, J⁵And J⁶No more than one of which is S
, D⁵, D⁶, J⁵And J⁶Is O and S, then D⁵, D⁶, J⁵ And J⁶One must be a covalent bond, and D⁵, D⁶, J⁵And J⁶ No more than four are N; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl
, Alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloa
Selected from the group consisting of lucoxy, hydroxyalkyl, aminoalkyl and cyano
Selected group; R¹⁶And R¹⁹Is, Q^bWhere R¹⁶And R¹⁹ More than one at the same time Q^bIs not, Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride, and
C (NR²⁵) NR²³R²⁴A group selected from the group consisting of: R²⁰, R²¹, R²³, R²⁴And R²⁵Is independently hydride and
A group selected from the group consisting of alkyl; Q^sIs CH₂Or a pharmaceutically acceptable salt thereof. 13. The formula: embedded image Wherein B is a compound of the formula: wherein R ³² , R ³³ , R ³⁴ , R ³⁵ and R ³⁶ are independently hydride, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy,
Amino, N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amide carbonyl, carboxy, represented by groups) selected from the group consisting of cyano and ^{Q b;} A is a single covalent _{bond, NH, N (CH 3)} , CH 2, CH 3 CH and _CH 2 C
Group is selected from the group consisting of H _2; M is a group 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,
A group selected from the group consisting of hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro and chloro; R ² is phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazoyl, A group selected from the group consisting of 3-isoxazolyl, 2-pyridyl and 3-pyridyl, wherein one carbon adjacent to the carbon at the binding site may be substituted with R ⁹ , Another adjacent carbon may be substituted by R ¹³ , adjacent to R ^9, and a carbon two atoms away from the carbon at the bonding site may be substituted by R ¹⁰ , adjacent to R ¹³ , carbon distant 2 atoms from the carbon of the binding site may be substituted with R ^12, the carbon adjacent to both R ¹⁰ and R ¹² are substituted in R ¹¹ ; R ^{9, R 11} and ^{R 13} are independently hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N- methylamino, N, N- dimethylamino, methylthio, trifluoromethyl, pentafluoroethyl , 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl,
A group selected from the group consisting of -hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy and cyano; R ¹⁰ and R ¹² are independently hydride, amidino, amidocarbonyl,
N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2, 2,2-trifluoroethyl, trifluoroacetamide, aminomethyl, N-methylamino, dimethylamino, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo and cyano group may be selected from the group consisting of; the ^{Y 0: 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 -2R 19 ^{Lysine, 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 -5-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 group is selected from the group consisting of thiazole; ^{R 16, R 17} , R ¹⁸ and R ¹⁹ are independently hydride, 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, tri Fluoromethoxy, fluoro, chloro, amidosulfonyl, N
- methylamide sulfonyl, hydroxymethyl, carboxy and groups selected from the group consisting of cyano; is ^{Q b, NR} 20 ^{R 21} and ^C (NR ²⁵⁾ group selected from the group consisting of ^NR 23 ^{R 24,} provided that the Q ^b group is attached directly to a carbon ^{atom; R 20, R 21, R} 23, R 24 and ^{R 25} are independently hydrido, groups selected from the group consisting of methyl and ethyl; ^{Q s} is, The compound according to claim 12, which is represented by CH ² ], or a pharmaceutically acceptable salt thereof. 14. 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-methoxyphenyl, 4-methoxyphenyl,
A is a group selected from the group consisting of 3-methylphenyl, 4-methylphenyl and phenyl; A is a single covalent bond, CH ₂ , CH ₃ CH, CF ₃ CH, NHC (O), CH ₂ CH ₂ and CH ₂ A group selected from the group consisting of CH ₂ CH ₂ ; M is a group selected from the group consisting of N and R ¹ -C; R ¹ is hydride, 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-amidinophenyl, 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, 3-cyanophenyl, 3-dimethylamino Phenyl, 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-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2- thienyl, 3-pyridyl, 4-pyridyl, group are selected from the group consisting of 2-thienyl and 3-thienyl; ^{Y 0 is: 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 -2R ^{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 group is selected from the group consisting of thiophene; ^{R 16} and ^{R 19} are independently hydrido, amidino, amino, amino methyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, groups selected from the group consisting of chloro and cyano; ^{R 16} and ^{R 19} may be a ^{Q b, where} 1 of ^{R 16} and ^{R 19} many than one is, that they are not simultaneously ^{Q b, Q b} is ^{Q be; R 17} and ^{R 18} are, independently, hydride, fluoro, chloro, hydroxy, hydroxymethyl, amino, Ca Group ^{Q b is} a ^{Q BE, here, Q BE} is hydrido, and selected from ^{C (NR} 2 ⁵⁾ the group consisting of ^NR 23 ^{R 24;} group selected from the group consisting of Bokishi and cyano R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydride and methyl; Q ^s is CH ₂ ; or a pharmaceutically acceptable compound thereof. salt. 15. B is 3-aminophenyl, 3-amidinophenyl, 4-
A group selected from the group consisting of amidinophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 4-methylphenyl and phenyl; wherein A is CH ₂ , NHC (O), CH ₂ CH ₂ and _CH 2 _CH 2 group is selected from the group consisting of CH _2; M is a group 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, Methylphenyl, phenyl, 3-trifluoroacetamidophenyl, 3-bromo-2-thiene Le,
A group selected from the group consisting of 2-thienyl and 3-thienyl; Y ⁰ is 5-amino-2-thienylmethyl, 4-amidinobenzyl, 2-fluoro-4-amidinobenzyl and 3-fluoro-4-amidino 15. The compound according to claim 14, which is a group selected from the group consisting of benzyl; or a pharmaceutically acceptable salt thereof. 16. The formula: embedded image[Where R²Is 3-aminophenyl, B is 3-chlorophenyl, A is CH₂CH ₂ , Y⁰Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is phenyl, A is CH₂, Y⁰Is 4-
Amidinobenzyl and M are CH; R²Is phenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰Is
, 4-amidinobenzyl and M are CH; R²Is 3-dimethylaminophenyl, B is phenyl, A is CH₂CH₂ , Y⁰Is 4-amidinobenzyl and M is CH; R²Is 2-methylphenyl, B is phenyl, A is CH₂CH₂, Y⁰Is
, 4-amidinobenzyl and M are CH; R²Is phenyl, B is 3-aminophenyl, A is C (O) NH, Y⁰Is
, 4-amidinobenzyl and M are CH; R²Is phenyl, B is 3-amidinophenyl, A is CH₂, Y⁰Is 4
-Amidinobenzyl and M are CH; R²Is 3- (N-methylamino) phenyl, B is phenyl, A is CH₂ CH₂, Y⁰Is 4-amidinobenzyl and M is CH; R²Is 3-methylsulfonamidophenyl, B is phenyl, A is CH₂ CH₂, Y⁰Is 4-amidinobenzyl and M is CH; R²Is phenyl, B is 4-amidinophenyl, A is CH₂, Y⁰Is 4
-Amidinobenzyl and M are CH; R²Is 3-methylaminophenyl, B is phenyl, A is CH₂CH₂,
Y⁰Is 4-amidinobenzyl and M is CH; R²Is phenyl, B is phenyl, A is CH₂, Y0 is 4-amidinobe
R and Z are CH; R²Is 3-methylphenyl, B is 4-phenyl, A is CH₂CH₂, Y ⁰ Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is 3-chlorophenyl, A is CH₂CH ₂ , Y⁰Is 4-amidinobenzyl and M is CCl; R²Is 3-aminophenyl, B is phenyl, A is CH₂, Y⁰Is 4-
Amidinobenzyl and M are CCl; R²Is phenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰Is
, 4-amidinobenzyl and M are CCl;²Is 3-dimethylaminophenyl, B is phenyl, A is CH₂CH₂ , Y⁰Is 4-amidinobenzyl and M is CCl; R²Is 2-methylphenyl, B is phenyl, A is CH₂CH₂, Y⁰Is
, 4-amidinobenzyl and M are CCl;²Is phenyl, B is 3-aminophenyl, A is C (O) NH, Y⁰Is
, 4-amidinobenzyl and M are CCl;²Is phenyl, B is 3-aminophenyl, A is CH₂, Y⁰Is 4-
Amidinobenzyl and M are CCl; R²Is 3- (N-methylamino) phenyl, B is phenyl, A is CH₂ CH₂, Y⁰Is 4-amidinobenzyl and M is CCl; R²Is 3-methylsulfonamidophenyl, B is phenyl, A is CH₂ CH₂, Y⁰Is 4-amidinobenzyl and M is CCl; R²Is phenyl, B is 4-amidinophenyl, A is CH₂, Y⁰Is 4
Amidinobenzyl and M are CCl; R²Is 3-methylaminophenyl, B is phenyl, A is CH₂CH₂,
Y⁰Is 4-amidinobenzyl and M is CCl; R²Is phenyl, B is phenyl, A is CH₂, Y⁰Is 4-Amidinobe
And M are CCl; R²Is 3-methylphenyl, B is 4-phenyl, A is CH₂CH₂, Y ⁰ Is 4-amidinobenzyl and M is CCl; R²Is 3-aminophenyl, B is 3-chlorophenyl, A is CH₂CH ₂ , Y⁰Is 4-amidinobenzyl and M is CF; R²Is 3-aminophenyl, B is phenyl, A is CH₂, Y⁰Is 4-
Amidinobenzyl and M are CF; R²Is phenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰Is
, 4-amidinobenzyl and M are CF; R²Is 3-dimethylaminophenyl, B is phenyl, A is CH₂CH₂ , Y⁰Is 4-amidinobenzyl and M is CF; R²Is 2-methylphenyl, B is phenyl, A is CH₂CH₂, Y⁰Is
, 4-amidinobenzyl and M are CF; R²Is phenyl, B is 3-aminophenyl, A is C (O) NH, Y⁰Is
, 4-amidinobenzyl and M are CF; R²Is phenyl, B is 3-aminophenyl, A is CH₂, Y⁰Is 4-
Amidinobenzyl and M are CF; R²Is 3- (N-methylamino) phenyl, B is phenyl, A is CH₂ CH₂, Y⁰Is 4-amidinobenzyl and M is CF; R²Is 3-methylsulfonamidophenyl, B is phenyl, A is CH₂ CH₂, Y⁰Is 4-amidinobenzyl and M is CF; R²Is phenyl, B is 4-amidinophenyl, A is CH₂, Y⁰Is 4
Amidinobenzyl and M are CF; R²Is 3-methylaminophenyl, B is phenyl, A is CH₂CH₂,
Y⁰Is 4-amidinobenzyl and M is CF; R²Is phenyl, B is phenyl, A is CH₂, Y⁰Is 4-Amidinobe
And M are CF; R²Is 3-methylphenyl, B is 4-phenyl, A is CH₂CH₂, Y ⁰ Is 4-amidinobenzyl and M is CF; R²Is 3-aminophenyl, B is 3-chlorophenyl, A is CH₂CH ₂ , Y⁰Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is phenyl, A is CH₂, Y⁰Is 4-
Amidinobenzyl and M are N; R²Is phenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰Is
, 4-amidinobenzyl and M are N; R²Is 3-dimethylaminophenyl, B is phenyl, A is CH₂CH₂ , Y⁰Is 4-amidinobenzyl and M is N; R²Is 2-methylphenyl, B is phenyl, A is CH₂CH₂, Y⁰Is
, 4-amidinobenzyl and M are N; R²Is phenyl, B is 3-aminophenyl, A is C (O) NH, Y⁰Is
, 4-amidinobenzyl and M are N; R²Is phenyl, B is 3-amidinophenyl, A is CH₂, Y⁰Is 4
Amidinobenzyl and M are N; R²Is 3- (N-methylamino) phenyl, B is phenyl, A is CH₂ CH₂, Y⁰Is 4-amidinobenzyl and M is N; R²Is 3-methylsulfonamidophenyl, B is phenyl, A is CH₂ CH₂, Y⁰Is 4-amidinobenzyl and M is N; R²Is phenyl, B is 4-amidinophenyl, A is CH₂, Y⁰Is 4
Amidinobenzyl and M are N; R²Is 3-methylaminophenyl, B is phenyl, A is CH₂CH₂,
Y⁰Is 4-amidinobenzyl and M is N; R²Is phenyl, B is phenyl, A is CH₂, Y⁰Is 4-Amidinobe
N and R are N; R²Is 3-methylphenyl, B is 4-phenyl, A is CH₂CH₂, Y ⁰ Is selected from the group represented by 4-amidinobenzyl and M is N]
Item 10. The compound according to item 9, or a pharmaceutically acceptable salt thereof. 17. The formula: embedded imageWherein B is hydride, C2-C8 alkyl, C3-C8 alkenyl, C3-C8
A group selected from the group consisting of alkynyl and C2-C8 haloalkyl, wherein
Each member of B is any carbon containing up to 6 atoms from the site of attachment of B to A,
R³², R³³, R³⁴, R³⁵And R³⁶One or more of the group consisting of
R may be substituted with³², R³³, R³⁴, R³⁵And R³⁶, Independently, hydride, ace
Toamide, haloacetamide, amidino, guanidino, alkoxy, hydroxy
, Amino, alkoxyamino, lower alkylamino, alkylthio, amido sulf
Honyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, alkyl
, Halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalco
Xy, carboxy, carboxamide, cyano and Q^bSelected from the group consisting of
A is a single covalent bond as well as (CH (R^Fifteen))_pa− (W⁷)_rrGroup consisting of
Wherein rr is an integer selected from 0 to 1 and pa is 0 to
An integer selected from 3 and W⁷Is (R⁷) NC (O) and N (R⁷) Or
A group selected from the group consisting of: R⁷Is a group selected from the group consisting of hydride, hydroxy and alkyl;^FifteenIs selected from the group consisting of hydride, halo, alkyl and haloalkyl
M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, hydroxy, hydroxyamino, amidino, amino, shea
No, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoal
Kill, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and
A group selected from the group consisting of halo; R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, O, S, NH and CH₂A group selected from the group consisting of
Q is a group selected from the group consisting of aryl and heteroaryl, wherein
One carbon adjacent to the carbon at the binding site is R⁹May be replaced by
Other carbons adjacent to the carbon at the position¹³May be substituted with⁹Adjacent to
, The carbon two atoms away from the carbon at the binding site is R¹⁰May be substituted with ¹³ And two carbons away from the carbon at the binding site are represented by R¹²Has been replaced by
May be R¹⁰And R¹²The carbon adjacent to both is R¹¹Has been replaced by
Or R⁹, R¹¹And R¹³Is independently hydride, hydroxy, amino, a
Midino, guanidino, lower alkylamino, alkylthio, alkylsulfone
Amide, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoa
Rukylamidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloa
Lucoxy, hydroxyalkyl, carboxy, carboxamide and cyano
A group selected from the group consisting of: R¹⁰And R¹²Is independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, al
Coxyamino, lower alkylamino, alkylsulfonamide, amidosulfoni
Monoalkylamidosulfonyl, dialkylamidosulfonyl, hydroxyal
Kill, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,
Selected from the group consisting of amidocarbonyl, halo, haloalkyl and cyano
Group; Y⁰Is represented by the formula (IV): (IV) (where D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from the group consisting of a bond, provided that more than one is a covalent bond
But not K²Are C and D⁵, D⁶, J⁵And J⁶O is more than one of
But D⁵, D⁶, J⁵And J⁶No more than one of which is S
, D⁵, D⁶, J⁵And J⁶Is O and S, then D⁵, D⁶, J⁵ And J⁶One must be a covalent bond, and D⁵, D⁶, J⁵And J⁶ No more than four are N; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl
, Alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloa
Selected from the group consisting of lucoxy, hydroxyalkyl, aminoalkyl and cyano
Selected group; R¹⁶And R¹⁹Is Q^bWhere R¹⁶And R¹⁹of
More than one but at the same time Q^bIs not, Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride and C (N
R²⁵) NR²³R²⁴And N (R²⁶) C (NR²⁵) N (R²³) (R^{2 4} A group selected from the group consisting of:²⁰And R²¹More than one
Are not simultaneously hydroxy, and R²³And R²⁴More than one of
, But not simultaneously hydroxy. R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
Q, a group selected from the group consisting of alkyl, and hydroxy;^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
3. The compound according to claim 2, which is represented by the formula: 18. B is hydride, ethyl, 2-propyl, 2-propenyl
, Propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butini
, Sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl,
1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentenyl
Nil, 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-he
Xenyl, 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-butyi
Nil, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-
Heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptini
5-Heptynyl, 2-heptyl, 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, 2,2,2-trifur
Oroethyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,
5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6
Of 3,6-pentafluorohexyl and 3,3,3-trifluoropropyl
A member selected from the group consisting of:
Any carbon, including up to the atom,³², R³³, R³⁴, R³⁵And R^{3 6} R may be substituted with one or more groups from the group consisting of:³², R³³, R³⁴, R³⁵And R³⁶But independently, hydride,
Dino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propo
Xy, hydroxy, amino, methoxyamino, ethoxyamino, acetamide,
Trifluoroacetamide, N-methylamino, dimethylamino, N-ethylamine
Mino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pen
Tafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pe
Nantafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoro
Roethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamide
Sulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydrido
Roxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydro
Xyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N
-Methylamidocarbonyl, N, N-dimethylamidocarbonyl, cyano and
Q^bA group selected from the group consisting of: A is a single covalent bond, NH, N (CH₃), N (OH), CH₂, CH₃CH,
CF₃CH, NHC (O), N (CH₃) C (O), C (O) NH, C (O) N
(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, And C
F₃CHCH₂A group selected from the group consisting of: M is N and R¹A group selected from the group consisting of: -C; R¹But hydride, hydroxy, amino, amidino, hydroxyamino,
Nomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl
, Ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Oroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydro
Xyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy
, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro and bromo
A group selected from the group consisting of: R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, O, S, NH and CH₂A group selected from the group consisting of
Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2
-Pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazo
Ryl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl
Ryl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyridyl
Midinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridinyl
A group selected from the group consisting of dazinyl and 1,3,5-triazin-2-yl
Where one carbon adjacent to the carbon at the binding site is R⁹May be replaced by
And the other carbon adjacent to the carbon at the binding site is R¹³May be substituted with ⁹ And two carbons away from the carbon at the binding site are represented by R¹⁰Has been replaced by
Well, R¹³And two carbons away from the carbon at the binding site are represented by R¹²Put in
May be replaced by R¹⁰And R¹²The carbon adjacent to both is R¹¹Replace with
R⁹, R¹¹And R¹³But independently, hydride, amidino, guanidino,
Carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy,
Isopropoxy, propoxy, hydroxy, amino, N-methylamino, N, N
-Dimethylamino, N-ethylamino, methylthio, ethylthio, isopropyl
Thio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Ethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy
, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, meta
N-sulfonamide, amidosulfonyl, N-methylamidosulfonyl, N, N-
Dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-h
Droxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidoca
Rubonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl and
A group selected from the group consisting of:¹⁰And R¹²But independently, hydride, amidino, guanidino, carbo
Xy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy
, Ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamido
No, ethoxyamino, acetamide, trifluoroacetamide, aminomethyl
, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,
N-ethylamino, methanesulfonamide, amidosulfonyl, N-methylamido
Dosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-
Droxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydrido
Roxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro,
A group selected from the group consisting of chloro, bromo and cyano; Y⁰But: 1-Q^b-4-Q^s-2-R¹⁶-3-R¹⁷−5-R¹⁸-6-R¹⁹Benze
, 2-Q^b−5-Q^s-6-R¹⁷-4-R¹⁸-2R¹⁹Pyridine, 3-Q^b-6-Q^s-2-R¹⁶−5-R¹⁸-4-R¹⁹Pyridine, 2-Q^b-4-Q^s-3-R¹⁶-6-R¹⁸Pyrazine, 3-Q^b-6-Q^s-2-R¹⁸−5-R¹⁸-4-R¹⁹Pyridazine, 2-Q^b−5-Q^s-6-R¹⁷-4-R¹⁸Pyrimidine, 5-Q^b-2-Q^s-3-R¹⁶-6-R¹⁹Pyrimidine, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Thiophene, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Thiophene, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Franc, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Franc, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Pyrrole, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Pyrrole, 4-Q^b-2-Q^s−5-R¹⁹Imidazole, 2-Q^b-4-Q^s−5-R¹⁷Imidazole, 3-Q^b−5-Q^s-4-R¹⁶Isoxazole, 5-Q^b-3-Q^s-4-R¹⁶Isoxazole, 2-Q^b−5-Q^s-4-R¹⁶Pyrazole, 4-Q^b-2-Q^s−5-R¹⁹Thiazole, and 2-Q^b−5-Q^s-4-R¹⁷A group selected from the group consisting of thiazoles; R¹⁶, R¹⁷, R¹⁸And R¹⁹But independently, hydride, methyl, ethi
Isopropyl, propyl, carboxy, amidino, guanidino, methoxy,
Ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl,
1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N
-Ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl
Tylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethi
Rusulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-tri
Fluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoro
Methoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bro
Mo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamide
Sulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl
The group consisting of 2,2,2-trifluoro-1-hydroxyethyl and cyano
A group selected from: R¹⁶And R¹⁹But Q^bWhere R¹⁶And R¹⁹of
More than one but at the same time Q^bIs not, Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride and C (N
R²⁵) NR²³R²⁴And N (R²⁶) C (NR²⁵) N (R²³) (R^{2 4} A group selected from the group consisting of:²⁰And R²¹More than one
Are not simultaneously hydroxy, and R²³And R²⁴More than one of
, But not simultaneously hydroxy; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶But independently, hydrangea
Of methyl, ethyl, propyl, butyl, isopropyl and hydroxy
Groups that can be selected from the group^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
The compound according to claim 17, or a pharmaceutically acceptable salt thereof. 19. B is hydride, 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-amidocarbonyl
Hexyl, 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-hydroxy
Hexyl, 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
A is a group selected from the group consisting of ropyl, 2-hexyl and 4-aminobutyl;₂, NHC (O), CH₂CH₂, CH₂CH₂CH ₂ And CH₃CHCH₂A group selected from the group consisting of: M is N and R¹A group selected from the group consisting of: -C; R¹But hydride, hydroxy, amino, amidino, hydroxyamino,
Nomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,
Droxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro
A group selected from the group consisting of b and chloro; R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, O, S, NH and CH₂A group selected from the group consisting of
Q is 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluoro
Rophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-meth
Toxylcarbonylphenyl, 3-amidinophenyl, 3-amino-2-methylphenyl
Phenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, benzyl
, 3-carboxyphenyl, 3-carboxy-5-aminophenyl, 3-carbo
Xy-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-methoxyphenyl
Phenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxyca
Rubonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2
-Methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-
Trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-to
Trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thiene
Nil, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl
And a group selected from the group consisting of: and 3-thienyl; Y⁰But: 1-Q^b-4-Q^s-2-R¹⁶-3-R¹⁷−5-R¹⁸-6-R¹⁹Benze
, 2-Q^b−5-Q^s-6-R¹⁷-4-R¹⁸-2R¹⁹Pyridine, 3-Q^b-6-Q^s-2-R¹⁶−5-R¹⁸-4-R¹⁹Pyridine, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Thiophene, and 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Selected from the group consisting of thiophenes
Group; R¹⁶And R¹⁹But independently, hydride, amidino, amino, aminomethy
Methoxy, methylamino, hydroxy, hydroxymethyl, fluoro,
A group selected from the group consisting of b and cyano; R¹⁶And R¹⁹But Q^bWhere R¹⁶And R¹⁹of
More than one but at the same time Q^bIs not, Q^bIs Q^beR¹⁷And R¹⁸But independently hydride, fluoro, chloro, hydroxy
Selected from the group consisting of, hydroxymethyl, amino, carboxy and cyano
Group; Q^bBut Q^be, Where Q^beIs a hydride, and C (NR²⁵) N
R²³R²⁴A group selected from the group consisting of: R²³, R²⁴, R²⁵And R²⁶Are independently hydride and methyl
A group selected from the group consisting of: Q^sBut CH₂19. The compound according to claim 18, which is: or a pharmaceutically acceptable salt thereof. 20. The formula: embedded imageWherein B is hydride, C2-C8 alkyl, C3-C8 alkenyl, C3-C8
A group selected from the group consisting of alkynyl and C2-C8 haloalkyl, wherein
Each member of B is any carbon containing up to 6 atoms from the site of attachment of B to A,
R³², R³³, R³⁴, R³⁵And R³⁶One or more of the group consisting of
R may be substituted with³², R³³, R³⁴, R³⁵And R³⁶, Independently, hydride, ace
Toamide, haloacetamide, amidino, guanidino, alkoxy, hydroxy
, Amino, alkoxyamino, lower alkylamino, alkylthio, amido sulf
Honyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, alkyl
, Halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalco
Xy, carboxy, carboxamide, cyano and Q^bSelected from the group consisting of
A is a single covalent bond and (CH (R^Fifteen))_pa− (W⁷)_rrSelected from
Where rr is an integer selected from 0 to 1 and pa is selected from 0 to 3.
Integer and W⁷Is N (R⁷); R⁷Is a group selected from the group consisting of hydride and alkyl;^FifteenIs selected from the group consisting of hydride, halo, alkyl and haloalkyl
M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, hydroxy, hydroxyamino, amidino, amino, shea
No, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoal
Kill, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and
A group selected from the group consisting of halo; R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond; Q is a group selected from the group consisting of aryl and heteroaryl, wherein
One carbon adjacent to the carbon at the binding site is R⁹May be replaced by
Other carbons adjacent to the carbon at the position¹³May be substituted with⁹Adjacent to
, The carbon two atoms away from the carbon at the binding site is R¹⁰May be substituted with ¹³ And the carbon two atoms away from the carbon at the binding site is R¹²Is replaced by
May be, R¹⁰And R¹²The carbon adjacent to both is R¹¹Has been replaced by
May be; R⁹, R¹¹, And R¹³Is independently hydride, hydroxy, amino,
Amidino, guanidino, lower alkylamino, alkylthio, alkoxy, al
Killsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamido
Dosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxya
Selected from the group consisting of alkyl, carboxy, carboxyamino and cyano
Group; R¹⁰And R¹²Is independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkyl, alkoxy, alkoxyamino, amino
Alkyl, hydroxy, amino, lower alkylamino, alkylsulfonamide
, Amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfo
Nil, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboal
From koxy, carboxy, carboxamide, carboxyalkyl and cyano
A group selected from the group consisting of: Y⁰Is of the formula (IV): (IV) (where D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from the group consisting of a bond, provided that more than one is a covalent bond
But not K²Are C and D⁵, D⁶, J⁵And J⁶O is more than one of
But D⁵, D⁶, J⁵And J⁶No more than one of which is S
, D⁵, D⁶, J⁵And J⁶Is O and S, then D⁵, D⁶, J⁵ And J⁶One must be a covalent bond, and D⁵, D⁶, J⁵And J⁶ No more than four are N; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl
, Alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloa
Selected from the group consisting of lucoxy, hydroxyalkyl, aminoalkyl and cyano
Selected group; R¹⁶And R¹⁹Is Q^bWhere R¹⁶And R¹⁹of
More than one but at the same time Q^bIs not, Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride and N (R ²⁶ ) C (NR²⁵) N (R²³) (R²⁴) And C (NR²⁵) NR²³R ²⁴ A group selected from the group consisting of: R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
Q is a group selected from the group consisting of^sIs CH₂] The compound of Claim 17 represented by these, or its pharmaceutically acceptable salt. 21. B is hydride, ethyl, 2-propenyl, 2-propyl, propyl, isopropyl, butyl, 2-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, -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-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 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-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl , 5,5,6,6,6-pentafluorohexyl and 3,3,3-trifluoropropyl, wherein each member of B is 5 members from the binding site of B to A Any carbon, up to and including an atom, may be substituted 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, independently, hydride, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N- methylamino, dimethylaminopyridine , Methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,
Chloro, bromo, amide sulfonyl, N- methylamide sulfonyl, hydroxymethyl, amidocarbonyl, carboxy, groups selected from the group consisting of cyano and ^{Q b;} A is a single covalent _{bond, NH, N (CH 3)} , CH ₂ , CH ₃ CH and CH ₂ C
A group selected from the group consisting of H ₂ ; A is CH ₂ N (CH ₃ ), CH ₂ N (CH ₂ CH ₃ ), CH ₂ CH ₂ N (C
H ₃ ) and a group which may be selected from the group consisting of CH ₂ CH ₂ N (CH ₂ CH ₃ ), wherein B is hydride; a group wherein M is selected from the group consisting of N and R ¹ -C ; R ¹ is the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro and chloro R ² is selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazoyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl and 3-pyridyl group, where one carbon adjacent to the carbon binding sites may be substituted with R ^9, bond Other carbon adjacent to the carbon atom may be substituted with R ^13, adjacent to R ^9, carbon distant 2 atoms from the carbon of the binding site may be substituted with R ^10, R The carbon adjacent to ¹³ and two atoms from the carbon at the binding site may be substituted for R ¹² , and the carbon adjacent to both R ¹⁰ and R ¹² may be substituted for R ¹¹ ; ⁹ , R ¹¹ and R ¹³ independently represent hydride, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N, N-dimethylamino, methylthio, trifluoromethyl, pentafluoroethyl, , 2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl,
A group selected from the group consisting of -hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy and cyano; R ¹⁰ and R ¹² are independently hydride, amidino, amidocarbonyl,
N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2, 2,2-trifluoroethyl, trifluoroacetamide, aminomethyl, N-methylamino, dimethylamino, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo and cyano group is selected from the group consisting of; is ^{Y 0: 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 -2R 19 ^{Lysine, 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 -5-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 group is selected from the group consisting of thiazole; ^{R 16, R 17} , R ¹⁸ and R ¹⁹ are independently hydride, 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, tri Fluoromethoxy, fluoro, chloro, amidosulfonyl, N
- methylamide sulfonyl, hydroxymethyl, group are selected from the group consisting of carboxy and cyano; ^{Q b is, NR 20 R 21, C (} NR 25) NR 23 R 24 and N ^{(R 26)}
A group selected from the group consisting of C (NR ²⁵ ) N (R ²³ ) (R ²⁴ ), provided that
Group ^{R 20, R 21, R 23} , R 24, R 25 and ^{R 26} are, independently, the hydride is selected from the group consisting of methyl and ethyl; the ^{Q b} group, which binds directly to a carbon atom; The compound according to claim 17, wherein Q ^s is a group represented by CH ₂ , or a pharmaceutically acceptable salt thereof. 22. B is hydride, 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-
A group selected from the group consisting of methylbutyl, 2-methylbutyl, (S) -2-methylbutyl, 3-aminopropyl, 2-hexyl and 4-aminobutyl; A is a single covalent bond, CH ₂ , CH ₃ CH and A group selected from the group consisting of CH ₂ CH ₂ ; M is a group selected from the group consisting of N and R ¹ -C; R ¹ is hydride, 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-amidinophenyl, 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-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarboxyphenyl, 2-methylaminophenyl, 3-methylaminophenyl,
2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3
-Trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-
Selected from the group consisting of trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl and 3-thienyl that group; ^{Y 0 is: 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 ^{-2R 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 group is selected from the group consisting of thiophene,; ^{R 16} and ^{R 19,} independently, Hydride, amidino, amino, aminomethyl, methoxy, methyl Amino, hydroxy, hydroxymethyl, fluoro, groups selected from the group consisting of chloro and cyano; ^{R 16} and ^{R 19} may be a ^{Q b, where} more than one of ^{R 16} and ^{R 19,} that they are not simultaneously ^{Q b, Q b} is ^{Q be; R 17} and ^{R 18} are, independently, hydride, fluoro, chloro, hydroxy, hydroxymethyl, amino, a group selected from the group consisting of carboxy and cyano ; Q ^b is ^a group represented by ^{Q bE, here, Q bE} is hydrido, and C (
NR ²⁵ ) a group selected from the group consisting of NR ²³ R ²⁴ ; a group wherein R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydride and methyl; Q ^s represents CH ₂ 22. The compound according to claim 21 or a pharmaceutically acceptable salt thereof. 23. B is hydride, 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-
A group selected from the group consisting of methylbutyl, 2-methylbutyl, (S) -2-methylbutyl, 3-aminopropyl, 2-hexyl and 4-aminobutyl; A is a single covalent bond, CH ₂ , CH ₃ CH, and _CH 2 CH groups selected from the group consisting of _2; ^{radicals R 1} is selected from the group consisting of hydrido, fluoro and chloro; M is a group selected from the group consisting of N and ^R 1 -C; R ² is 5-amino-2-fluorophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, 3-carboxyphenyl, 3-cyanophenyl, 3-methoxycarbonyl phenyl, group is selected from the group consisting of phenyl and 3-pyridyl; is ^{Y 0,} 5-amino-2-thienylmethyl, 4- Amijinobe The compound or pharmaceutically acceptable salt thereof according to claim 22, wherein a is; Jill, 2-fluoro-4-amidino benzyl and 3-fluoro-4-groups selected from the group consisting of amidino benzyl. 24. The formula: embedded image[Where: R²Is 3-aminophenyl, B is 2,2,2-trifluoroethyl, A is
, Single bond, Y⁰Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is (S) -2-butyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is CH; R²Is 5-amino-2-fluorophenyl, B is isopropyl, A is
Join, Y⁰Is 4-amidinobenzyl and M is CH; R²Is 2-methyl-3-aminophenyl, B is isopropyl, A is single bond
If Y⁰Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is ethyl, A is a single bond, Y⁰Is 4-A
Midinobenzyl and M are CH; R²Is 3-aminophenyl, B is ethyl, A is a single bond, Y⁰Is 4-A
Midino-2-fluorobenzyl and M are CH; R²Is 3-aminophenyl, B is 2-propenyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are CH; R²Is 3-aminophenyl, B is isopropyl, A is a single bond, Y⁰Is
4-Amidino-2-fluorobenzyl and M are CH; R²Is 3-aminophenyl, B is isopropyl, A is a single bond, Y⁰Is
4-amidinobenzyl and M are CH; R²Is 3-aminophenyl, B is 2-butyl, A is a single bond, Y⁰Is 4
-Amidinobenzyl and M are CH; R²Is 3-aminophenyl, B is (R) -2-butyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is 2-propynyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are CH; R²Is 3-aminophenyl, B is 3-phenyl, A is a single bond, Y⁰Is
4-amidinobenzyl and M are CH; R²Is 3-aminophenyl, B is hydride, A is CH₂, Y⁰Is 4-
Amidinobenzyl and M are CH; R²Is 3-aminophenyl, B is ethyl, A is CH₂, Y⁰Is 4-A
Midinobenzyl and M are CH; R²Is 3-aminophenyl, B is 2-methylpropyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is 2-propyl, A is CH₃CH, Y⁰ Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is propyl, A is a single bond, Y⁰Is 4-
Amidino-2-fluorobenzyl and M are CH; R²Is 3-aminophenyl, B is 6-amidocarbonylhexyl, A is
Single bond, Y⁰Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is tert-butyl, A is a single bond, Y⁰ Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is tert-butyl, A is a single bond, Y⁰ Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is 3-hydroxypropyl, A is a single bond
, Y⁰Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is 2-methylpropyl, A is a single bond, Y ⁰ Is 4-amidino-2-fluorobenzyl and M is CH; R²Is 3-aminophenyl, B is butyl, A is a single bond, Y⁰Is 4-A
Midinobenzyl and M are CH; R²Is 3-aminophenyl, B is 3-methoxy-2-propyl, A is
Join, Y⁰Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is 3-methoxy-2-propyl, A is
Join, Y⁰Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is 2-methoxy-2-ethyl, A is single bond
If Y⁰Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is 2-propyl, A is a single bond, Y⁰Is
5-amidino-2-thienylmethyl and M are CH; R²Is 3-aminophenyl, B is 2-propyl, A is a single bond, Y⁰Is
4-amidino-3-fluorobenzyl and M are CH; R²Is 3-carboxyphenyl, B is 2-propyl, A is a single bond, Y⁰ Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is 2-propyl, A is a single bond, Y⁰Is
4-amidino-3-fluorobenzyl and M are CH; R²Is 3-aminophenyl, B is 2,2,2-trifluoroethyl, A is
, Single bond, Y⁰Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is (S) -2-butyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is N; R²Is 5-amino-2-fluorophenyl, B is isopropyl, A is
Join, Y⁰Is 4-amidinobenzyl and M is N; R²Is 2-methyl-3-aminophenyl, B is isopropyl, A is single bond
If Y⁰Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is ethyl, A is a single bond, Y⁰Is 4-A
Midinobenzyl and M are N; R²Is 3-aminophenyl, B is ethyl, A is a single bond, Y⁰Is 4-A
Midino-2-fluorobenzyl and M are N; R²Is 3-aminophenyl, B is 2-propenyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are N; R²Is 3-aminophenyl, B is isopropyl, A is a single bond, Y⁰Is
4-amidino-2-fluorobenzyl and M are N; R²Is 3-aminophenyl, B is isopropyl, A is a single bond, Y⁰Is
4-amidinobenzyl and M are N; R²Is 3-aminophenyl, B is 2-butyl, A is a single bond, Y⁰Is 4
Amidinobenzyl and M are N; R²Is aminophenyl, B is (R) -2-butyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are N; R²Is 3-aminophenyl, B is 2-propynyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are N; R²Is 3-aminophenyl, B is 3-pentyl, A is a single bond, Y⁰Is
4-amidinobenzyl and M are N; R²Is 3-aminophenyl, B is hydride, A is CH₂, Y⁰Is 4-
Amidinobenzyl and M are N; R²Is 3-aminophenyl, B is ethyl, A is CH₂, Y⁰Is 4-A
Midinobenzyl and M are N; R²Is 3-aminophenyl, B is 2-methylpropyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is 2-propyl, A is CH₃CH, Y⁰ Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is propyl, A is a single bond, Y⁰Is 4-
Amidino-2-fluorobenzyl and M are N; R²Is 3-aminophenyl, B is 6-aminocarbonylhexyl, A is
Single bond, Y⁰Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is tert-butyl, A is a single bond, Y⁰ Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is tert-butyl, A is a single bond, Y⁰ Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is 3-hydroxypropyl, A is a single bond
, Y⁰Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is 2-methylpropyl, A is a single bond, Y ⁰ Is 4-amidino-2-fluorobenzyl and M is N; R²Is 3-aminophenyl, B is butyl, A is a single bond, Y⁰Is 4-A
Midinobenzyl and M are N; R²Is 3-aminophenyl, B is 3-methoxy-2-propyl, A is
Join, Y⁰Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is 3-methoxy-2-propyl, A is
Join, Y⁰Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is 2-methoxy-2-ethyl, A is single bond
If Y⁰Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is 2-propyl, A is a single bond, Y⁰Is
5-amidino-2-thienylmethyl and M are N; R²Is 3-aminophenyl, B is 2-propyl, A is a single bond, Y⁰Is
4-amidino-3-fluorobenzyl and M are N; R²Is 3-carboxyphenyl, B is 2-propyl, A is a single bond, Y⁰ Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is 2-propyl, A is a single bond, Y⁰Is
18. The compound of claim 17, wherein 4-amidino-3-fluorobenzyl and M are selected from the group consisting of N] or a pharmaceutically acceptable salt thereof.
salt. 25. The formula: embedded imageWherein B is a group consisting of C3-C7 cycloalkyl and C4 saturated heterocyclyl
Groups selected from wherein each carbon is R³³May be substituted into
Ring carbons other than the ring carbon of the bonding site of B may be substituted with oxo,
Provided that no more than one ring carbon is simultaneously substituted with oxo,
The ring carbon and nitrogen adjacent to the carbon at the site are R⁹Or R¹³Has been replaced by
Well, R⁹A ring carbon or nitrogen adjacent to the position and up to 2 atoms from the point of attachment
, R¹⁰May be substituted with¹³Adjacent to the position, 2 atoms away from the binding site
And the ring carbon or nitrogen is R¹²May be substituted, 3 atoms from the binding site
Away, R¹⁰The ring carbon adjacent to the position is R¹¹May be replaced by
Three atoms away from the¹²The ring carbon adjacent to the position is R³³Even if
Well, and the ring carbon atom and R¹¹And R³³Ring adjacent to the position
Carbon is R³⁴May be substituted; R⁹, R¹¹And R¹³Is independently hydride, hydroxy, amino, a
Midino, guanidino, lower alkylamino, alkylthio, alkylsulfone
Amide, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoa
Rukylamidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloa
Lucoxy, hydroxyalkyl, carboxy, carboxamide and cyano
A group selected from the group consisting of: R¹⁰And R¹²Is independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkyl, alkoxy, hydroxy, amino, al
Coxyamino, lower alkylamino, alkylsulfonamide, amidosulfoni
, Monoalkylamidosulfonyl, dialkylamidosulfonyl, hydroxy
Alkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl
Amide, amide carbonyl, halo, haloalkyl and cyano
Group; R³³And R³⁴Is independently hydride, acetamide, haloacetamide
Do, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamido
, Lower alkylamino, alkylthio, amidosulfonyl, monoalkylamido
Dosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl,
Haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carbo
Xyxamide, cyano and Q^bA is a single covalent bond as well as ((CH (R^Fifteen))_pa− (W⁷)_rrConsisting of
A group selected from the group, where rr is an integer selected from 0 to 1, pa is 0
An integer selected from ~ 3, and W⁷Is (R⁷) NC (O) and N (R⁷)
A group selected from the group consisting of: R⁷Is a group selected from the group consisting of hydride, hydroxy and alkyl;^FifteenIs selected from the group consisting of hydride, halo, alkyl and haloalkyl
M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, hydroxy, hydroxyamino, amidino, amino, shea
No, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoal
Kill, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and
A group selected from the group consisting of halo; R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, O, S, NH and CH₂A group selected from the group consisting of
Q is a group selected from the group consisting of aryl and heteroaryl, wherein
The carbon adjacent to the carbon at the binding site is R⁹May be substituted with
The other carbon adjacent to the element is R¹³May be substituted with⁹Adjacent to
And the carbon two atoms away from the carbon at the bond site is R¹⁰May be substituted with ¹³ And two carbons away from the carbon at the binding site are represented by R¹²Replaced by
May be R¹⁰And R¹²The adjacent carbons of both binding sites are R¹¹ May be substituted; Y⁰Is represented by the formula (IV): (IV) (where D⁵, D⁶, J⁵And J⁶Independently represent C, N, O, S and shared
A group selected from the group consisting of a bond, provided that more than one is a covalent bond
But not K²Are C and D⁵, D⁶, J⁵And J⁶O is more than one of
But D⁵, D⁶, J⁵And J⁶No more than one of which is S
, D⁵, D⁶, J⁵And J⁶Is O and S, then D⁵, D⁶, J⁵ And J⁶One must be a covalent bond, and D⁵, D⁶, J⁵And J⁶ No more than four are N; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl
, Alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloa
Selected from the group consisting of lucoxy, hydroxyalkyl, aminoalkyl and cyano
Selected group; R¹⁶And R¹⁹Is Q^bWhere R¹⁶And R¹⁹of
More than one but at the same time Q^bIt will not be, Q^bIs Q^be; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride, and
C (NR²⁵) NR²³R²⁴A group selected from the group consisting of:²⁰You
And R²¹Are not simultaneously hydroxy, and R^{2 3} And R²⁴Are not simultaneously hydroxy. R²⁰, R²¹, R²³, R²⁴And R²⁵Are, independently, hydride, al
A group selected from the group consisting of kill and hydroxy; Q^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
Or a pharmaceutically acceptable salt thereof. 26. When B is cyclopropyl, cyclobutyl, oxetane-3-
Yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl,
Thiaethane-3-yl, cyclopentyl, cyclohexyl, norbornyl, bis
Selected from the group consisting of clo [3.1.0] hexane-6-yl and cycloheptyl
Where each ring carbon beam is represented by R³³May be replaced by
The ring carbon and nitrogen adjacent to the carbon at the position⁹Or R¹³Even if
Well, R⁹Ring carbon two atoms away from the bonding site adjacent to the¹⁰Is replaced by
May be R¹³The ring carbon adjacent to the site and two atoms away from the binding site is R^{1 2} May be substituted; R⁹, R¹¹, And R¹³But independently, hydride, amidino, guanidino
, Carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy
, Isopropoxy, propoxy, hydroxy, amino, N-methylamino, N,
N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropyl
Luthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Roethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
Tansulfonamide, amidosulfonyl, N-methylamidosulfonyl, N, N
-Dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-
Hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amide
Carbonyl, N-methylamidocarbonyl, N, N-dimethylamidocarbonyl
R is a group selected from the group consisting of:¹⁰And R¹²But independently, hydride, amino, guanidino, carboki
Carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy,
Ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino
, Ethoxyamino, acetamide, trifluoroacetamide, aminomethyl,
1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N
-Ethylamino, methanesulfonamide, amidosulfonyl, N-methylamide
Sulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl, 1-hydrido
Roxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydro
Xyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N
-Methylamidocarbonyl, N, N-dimethylamidocarbonyl, fluoro,
A group selected from the group consisting of loro, bromo and cyano; R³³And R³⁴But independently, hydride, amidino, guanidino, carbo
Xy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino
, Methoxyamino, ethoxyamino, acetamide, trifluoroacetamide
, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethyl
Thio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2
, 2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
Trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro,
Loro, bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dim
Tylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydro
Xyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycal
Bonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl
, N, N-dimethylamidocarbonyl, cyano and Q^bSelected from the group consisting of
A is a single covalent bond, NH, N (CH₃), N (OH), CH₂, CH₃CH,
CF₃CH, NHC (O), N (CH₃) C (O), C (O) NH, C (O) N
(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂And CF ₃ CHCH₂A group selected from the group consisting of: M is N and R¹A group selected from the group consisting of: -C; R¹But hydride, hydroxy, amino, amidino, hydroxyamino,
Nomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl
, Ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Oroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydro
Xyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy
, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro and bromo
A group selected from the group consisting of: R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, O, S, NH and CH₂A group selected from the group consisting of
Q is phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2
-Pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazo
Ryl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl
Ryl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyridyl
Midinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridinyl
A group selected from the group consisting of dazinyl and 1,3,5-triazin-2-yl
Where one carbon adjacent to the carbon at the binding site is R⁹May be replaced by
And the other carbon adjacent to the carbon at the binding site is R¹³May be substituted with ⁹ The carbon adjacent to the site and two atoms away from the carbon at the binding site is R¹⁰Is replaced by
May be, R¹³Adjacent to the carbon atom and two atoms away from the carbon at the binding site is R^{1 2} May be substituted with¹⁰And R¹²The carbon adjacent to both is R¹¹ May be substituted; Y⁰But: 1-Q^b-4-Q^s-2-R¹⁶-3-R¹⁷−5-R¹⁸-6-R¹⁹Benze
, 2-Q^b−5-Q^s-6-R¹⁷-4-R¹⁸-2R¹⁹Pyridine, 3-Q^b-6-Q^s-2-R¹⁶−5-R¹⁸-4-R¹⁹Pyridine, 2-Q^b-4-Q^s-3-R¹⁶-6-R¹⁸Pyrazine, 3-Q^b-6-Q^s-2-R¹⁸−5-R¹⁸-4-R¹⁹Pyridazine, 2-Q^b−5-Q^s-6-R¹⁷-4-R¹⁸Pyrimidine, 5-Q^b-2-Q^s-3-R¹⁶-6-R¹⁹Pyrimidine, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Thiophene, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Thiophene, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Franc, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Franc, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Pyrrole, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Pyrrole, 4-Q^b-2-Q^s−5-R¹⁹Imidazole, 2-Q^b-4-Q^s−5-R¹⁷Imidazole, 3-Q^b−5-Q^s-4-R¹⁶Isoxazole, 5-Q^b-3-Q^s-4-R¹⁶Isoxazole, 2-Q^b−5-Q^s-4-R¹⁶Pyrazole, 4-Q^b-2-Q^s−5-R¹⁹Thiazole, and 2-Q^b−5-Q^s-4-R¹⁷A group selected from the group consisting of thiazoles; R¹⁶, R¹⁷, R¹⁸And R¹⁹But independently, hydride, methyl, ethi
Isopropyl, propyl, carboxy, amidino, guanidino, methoxy,
Ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl,
1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N
-Ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl
Thimethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,
Ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-
Trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoro
Oromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro,
Bromo, amidosulfonyl, N-methylamidosulfonyl, N, N-dimethyla
Midosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy
Consists of chill, 2,2,2-trifluoro-1-hydroxyethyl and cyano
A group selected from the group; R¹⁶And R¹⁹But Q^bWhere R¹⁶And R¹⁹of
More than one but at the same time Q^bIs not, Q^bIs Q^be; Q^bBut Q^beAnd here, Q^beIs a hydride, and C (NR^{2 5} ) NR²³R²⁴A group selected from the group consisting of:²³And R²⁴ No more than one are simultaneously hydroxy; R²³, R²⁴, And R²⁵Are independently hydride, methyl, ethyl and
A group selected from the group consisting of:^sIs a single covalent bond, CH₂And CH₂CH₂A group selected from the group consisting of
26. The compound according to claim 25, or a pharmaceutically acceptable salt thereof. 27. B is cyclopropyl, cyclobutyl, cyclopentyl,
Cyclohexyl, cycloheptyl, 2- (2R) -bicyclo [2.2.1] -heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,
A group selected from the group consisting of azetidin-3-yl and bicyclo [3.1.0] hexan-6-yl; wherein A is CH ₂ , NHC (O), CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ A group selected from the group consisting of: N is a group selected from the group consisting of N and R ¹ -C; R ¹ is a hydride, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, groups selected from the group consisting of fluoro and chloro; R ² is a group represented by Z 0 ^-Q; is Z ^0, a single covalent bond, O, S, groups selected from the group consisting of NH and CH _2; is Q, 5-amino-3-amido-carbonyl-phenyl, 5-amino 2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl, 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,
-Cyanophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 3-
Fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3
-Hydroxyphenyl, 3-methanesulfonylaminophenyl, 3-methoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, -Trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-
3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-
Group is selected from the group consisting of thienyl and ^{3-thienyl; 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 -2R 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 group is selected from the group consisting ^{-4-R 17} thiophene; ^{R 16} and R ¹⁹ is independently a group selected from the group consisting of hydride, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro and cyano; R ¹⁶ and R ¹⁹ are Q ^b Yes, but No more than one of R ¹⁶ and R ¹⁹ can be Q ^b at the same time, and Q ^b is Q ^be ; R ¹⁷ and R ¹⁸ are independently hydride, fluoro, chloro, hydroxy, hydroxymethyl, amino , group are selected from the group consisting of carbonyl and cyano; ^{Q b is Q bE, here, Q bE} is hydrido, are selected and from ^{C (NR} 2 ⁵⁾ the group consisting of ^NR 23 ^{R 24} 26. The compound according to claim 25, wherein R ²³ , R ²⁴ and R ²⁵ are independently selected from the group consisting of hydride and methyl; and Q ^s is a group represented by CH _2. Above acceptable salts. 28. The formula: embedded image Wherein; B is C3-C7 cycloalkyl and C4 group selected from the group consisting of saturated heterocyclyl, where each of the carbon may be substituted with R ^33, binding sites of B to A Ring carbons other than the ring carbons may be substituted with oxo,
However, the ring carbon and nitrogen adjacent to the carbon at the bond position, wherein more than one ring carbon is not simultaneously substituted with oxo, may be substituted with R ⁹ or R ¹³ , and R ⁹ A ring carbon or nitrogen adjacent to and two atoms away from the bonding site may be substituted with R ^10, and a ring carbon or nitrogen adjacent to position R ¹³ and two atoms away from the bonding site is substituted with R ¹² An optionally substituted ring carbon 3 atoms away from the bonding site and the ring carbon adjacent to position R ¹⁰ may be substituted with R ¹¹ , a ring carbon 3 atoms away from the bonding site and R ^{12 May} be substituted with R ³³ , and the ring carbon atom at the binding site and the ring carbons adjacent to R ¹¹ and R ³³ may be substituted with R ³⁴ ; ^{9, R 11} and ^{R 13,} Germany Hydride, hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxy Groups selected from the group consisting of amide and cyano; R ¹⁰ and R ¹² are independently hydride, acetamido, haloacetamide, amidino, guanidino, alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower alkyl Amino, alkylsulfonamide, amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, hydroxyalkyl, aminoalkyl, halo, Roarukiru, carboalkoxy, carboxy, carboxyalkyl, carboxyamide and groups selected from the group consisting of cyano; R ³³ and R ³⁴ are independently hydrido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxy, amino, lower R ³³ is a group selected from the group consisting of alkylamino, alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamide and cyano; , ^{Q b,} which may be; a is a single covalent bond and _{^{((CH (R 15))}} pa - (W 7) a group selected from the group consisting of _rr, here, rr from 0-1 An integer to be selected, a is 0
And W ⁷ is N (R ⁷ ); R ⁷ is a group selected from the group consisting of hydride and alkyl; R ¹⁵ is a group selected from hydride, halo, alkyl and haloalkyl A group selected from the group consisting of N and R ¹ -C; R ¹ is a hydride, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, A group selected from the group consisting of aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R ² is a group represented by Z ⁰ -Q; Z ⁰ is a single covalent bond; A group selected from the group consisting of aryl, wherein
The carbon adjacent to the carbon at the binding site may be substituted with R ⁹ , and the other carbon adjacent to the carbon at the binding site may be substituted with R ¹³ , adjacent to R ⁹ , The carbon two atoms away from the carbon of R may be substituted with R ¹⁰ , the carbon adjacent to R ¹³ and two atoms away from the carbon at the bonding site may be substituted with R ¹² , and R ¹⁰ And adjacent carbons of both the binding sites of R ¹² may be substituted with R ¹¹ ; R ⁹ , R ¹¹ and R ¹³ are independently hydride, hydroxy, amino, amidino, guanidino, lower alkylamino , Alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxya Kill, carboxy, groups selected from the group consisting of carboxamide and cyano; R ¹⁰ and R ¹² are independently hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyalkyl, aminoalkyl, hydroxy Selected from the group consisting of amino, lower alkylamino, alkylsulfonamide, amidosulfonyl, monoalkylamidosulfonyl, dialkylamidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxamide, carboxyalkyl and cyano Y ⁰ is a group represented by the formula (IV): (IV) wherein D ⁵ , D ⁶ , J ⁵ and J ⁶ are independently a group selected from the group consisting of C, N, O, S and a covalent bond, provided that more than one is Being not a covalent bond, K ² is not O, more than one of C, D ⁵ , D ⁶ , J ⁵ and J ⁶ , and K ² is a member of D ⁵ , D ⁶ , J ⁵ and J ⁶ . More than one cannot be S, and if two of D ⁵ , D ⁶ , J ⁵ and J ⁶ are O and S, one of D ⁵ , D ⁶ , J ⁵ and J ⁶ is It must be a covalent bond and no more than four of D ⁵ , D ⁶ , J ⁵ and J ⁶ can be N; R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ are independently Hydride, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
R ¹⁶ and R ¹⁹ are a group selected from the group consisting of lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and cyano; ^b , provided that more than one of R ¹⁶ and R ¹⁹ are not simultaneously Q ^b , where Q ^b is Q ^be ; Q ^b is NR ²⁰ R ²¹ , Q ^be , where , Q ^be is hydride, and a group selected from the group consisting of C (NR ²⁵ ) NR ²³ R ²⁴ ; R ²⁰ , R ²¹ , R ²³ , R ²⁴ and R ²⁵ are independently hydride and alkyl group is selected from the group consisting of; Q ^s is claim 25 represented by the radical represented by CH ₂₎ Compound or a pharmaceutically acceptable salt thereof. 29. B is cyclopropyl, cyclobutyl, cyclopentyl,
Cyclohexyl, cycloheptyl, 2- (2R) -dicyclo [2.2.1] -hep
Chill, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,
Consists of azetidin-3-yl and bicyclo [3.1.0] hexan-6-yl
A group selected from the group wherein each ring carbon is R³³May be replaced by
, The ring carbon and nitrogen adjacent to the carbon at the site of attachment are R⁹Or R¹³Is replaced by
May be R⁹Ring carbon two atoms away from the carbon at the site of attachment is R ¹⁰ May be substituted with¹³Two atoms from the carbon at the binding site
The distant ring carbon is R¹²May be substituted; R⁹, R¹¹, And R¹³But independently hydride, methyl, ethyl, meth
Xy, ethoxy, hydroxy, amino, N-methylamino, N, N-dimethyla
Mino, methylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-
Trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methyl
Luamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, cal
A group selected from the group consisting of boxy and cyano; R¹⁰And R¹²Is independently hydride, amidino, amide carbonyl,
N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy
, Hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy
Chill, carboxy, carboxymethyl, amino, acetamido, trifluorome
Chill, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoro
Acetamide, aminomethyl, N-methylamino, dimethylamino, amide sulf
Phonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl,
Selected from the group consisting of toxic, fluoro, chloro, bromo and cyano
Group to be used; R³³Are independently hydride, amidino, guanidino, methyl, ethyl,
Toxic, ethoxy, hydroxy, carboxy, amino, N-methylamino, dime
Tylamino, methylthio, ethylthio, trifluoromethyl, pentafluoroe
Chill, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidos
Ruphonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl
, Cyano and Q^bA group selected from the group consisting of: A is a single covalent bond, NH, N (CH₃), CH₂, CH₃CH, CH₂CH₂ And CH₂CH₂CH₂A group selected from the group consisting of: M is N and R¹A group selected from the group consisting of: -C; R¹But hydride, hydroxy, amino, amidino, hydroxyamino,
Nomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,
Droxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro
A group selected from the group consisting of b and chloro; R²Is phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazo
Ryl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl and 3-pyridyl
A group selected from the group consisting of: wherein one carbon adjacent to the carbon at the binding site is
, R⁹And the other carbon adjacent to the carbon at the bonding site is R¹³ May be substituted with⁹Adjacent to and two atoms away from the carbon at the binding site
Is R¹⁰May be substituted with¹³, And two atoms from the carbon at the binding site
The separated carbon is R¹²May be substituted with¹⁰And R¹²Next to both
The carbon in contact is R¹¹May be substituted; Y⁰But: 1-Q^b-4-Q^s-2-R¹⁶-3-R¹⁷−5-R¹⁸-6-R¹⁹Benze
, 2-Q^b−5-Q^s-6-R¹⁷-4-R¹⁸-2R¹⁹Pyridine, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Thiophene, 3-Q^b-6-Q^s-2-R¹⁶−5-R¹⁸-4-R¹⁹Pyridine, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Thiophene, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Franc, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Franc, 3-Q^b−5-Q^s-4-R¹⁶-2-R¹⁹Pyrrole, 2-Q^b−5-Q^s-3-R¹⁶-4-R¹⁷Pyrrole, 4-Q^b-2-Q^s−5-R¹⁹Thiazole, and 2-Q^b−5-Q^s-4-R¹⁷A group selected from the group consisting of thiazoles; R¹⁶, R¹⁷, R¹⁸And R¹⁹But independently, hydride, methyl, ethi
, Amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1
-Aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, methyl
Luthio, ethylthio, trifluoromethylthio, methylsulfinyl, methyls
Ruphonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Oroethyl, trifluoromethoxy, fluoro, chloro, amidosulfonyl, N
-Consisting of methylamidosulfonyl, hydroxymethyl, carboxy and cyano
A group selected from the group consisting of^bIs NR²⁰R²¹, And C (NR²⁵) NR²³R²⁴Group consisting of
A group selected from^bIs directly attached to a carbon atom; R²⁰, R²¹, R²³, R²⁴And R²⁵But independently, hydride, meth
A group selected from the group consisting of^sBut CH₂29. The compound according to claim 28, or a pharmaceutically acceptable salt thereof. 30. B is cyclopropyl, cyclobutyl, cyclopentyl,
Cyclohexyl, 2- (2R) -bicyclo [2.2.1] -heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl and azetidin-
A group selected from the group consisting of 3-yl; A is a single covalent bond, a group selected from the group consisting of CH ₂ , NHC (O), CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; A group selected from the group consisting of N and R ¹ -C; R ¹ is a group selected from the group consisting of hydride, hydroxy, amino, methyl, trifluoromethyl, fluoro and chloro; R ² is 3-amino phenyl, 2,6-dichlorophenyl, 2-hydroxyphenyl, 5-amino-2-thienyl and 3-group selected from the group consisting of thienyl; ^{Y 0 is: 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 Group is selected from the group consisting of ⁷ thiophene; R ¹⁶ and R ¹⁹ are independently hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, from the group consisting of chloro and cyano The groups R ¹⁶ and R ¹⁹ selected may be Q ^b , provided that no more than one of R ¹⁶ and R ¹⁹ are simultaneously Q ^b and Q ^b is Q ^be ; R ¹⁷ And R ¹⁸ is independently a group selected from the group consisting of hydride, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, and cyano; Q ^b is Q ^be , wherein Q ^be is hydride , and the and ^{C (NR} 2 ⁵⁾ groups selected from the group consisting of ^{NR 23 R 24; R 23,} R 24, and ^{R 25} is , Independently, hydride and groups selected from the group consisting of methyl; acceptable salt compound or a pharmaceutically claim 29, wherein a is; Q ^s is a group represented by CH _2. 31. B is cyclopropyl, cyclobutyl, cyclopentyl,
Cyclohexyl, 2- (2R) -bicyclo [2.2.1] -heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl and azetidin-
A group selected from the group consisting of 3-yl; A is a single covalent bond, a group selected from the group consisting of CH ₂ , CH ₂ CH ₂ and CF ₃ CHCH ₂ ; M is a group selected from N and R ¹ -C R ¹ is a group selected from the group consisting of hydride, fluoro and chloro; R ² is 3-aminophenyl, 2,6-dichlorophenyl, 2-hydroxyphenyl, phenyl, 5- A group selected from the group consisting of amino-2-thienyl and 3-thienyl; Y ⁰ is 5-amino-2-thienylmethyl, 4-amidinobenzyl, 2-fluoro-4-amidinobenzyl and 3-fluoro-4 Or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of -amidinobenzyl. 32. The formula: embedded image[Wherein, R²Is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are CH; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-Amidino-2-fluorobenzyl and M are CH; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-amidinobenzyl and M are CH; R²Is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y⁰Is
, 4-amidino-2-fluorobenzyl, and M are CH; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-amidinobenzyl and M are CH; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-amidino-3-fluorobenzyl and M are CH; R²Is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are CH; R²Is 5-amino-2-thienyl, B is cyclobutyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is cyclopropyl, A is CH₂, Y⁰Is
, 4-amidinobenzyl and M are CH; R²Is 3-aminophenyl, B is 2- (2R) -bicyclo [2.2.1]-
Heptyl, A is a single bond, Y⁰Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y⁰Is
, 4-amidino-2-fluorobenzyl and M are CH; R²Is 3-aminophenyl, B is cyclohexyl, A is CH₂CH₂,
Y⁰Is 4-amidinobenzyl and M is CH; R²Is 2-hydroxyphenyl, B is cyclobutyl, A is a single bond, Y⁰ Is 4-amidinobenzyl and M is CH; R²Is phenyl, B is cyclobutyl, A is a single bond, Y⁰Is 4-Amidi
Nobenzyl and M are CH; R²Is 3-thienyl, B is cyclobutyl, A is a single bond, Y⁰Is 4-A
Midinobenzyl and M are CH; R²Is 2,6-dichlorophenyl, B is cyclobutyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is CH; R²Is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are N; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-amidino-2-fluorobenzyl and M are N; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-amidinobenzyl and M are N; R²Is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y⁰Is
, 4-amidino-2-fluorobenzyl and M are N; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-amidinobenzyl and M are N; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-amidino-3-fluorobenzyl and M are N; R²Is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are N; R²Is 5-amino-2-thienyl, B is cyclobutyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is cyclopropyl, A is CH₂, Y⁰Is
, 4-amidinobenzyl and M are N; R²Is 3-aminophenyl, B is 2- (2R) -bicyclo [2.2.1]-
Heptyl, A is a single bond, Y⁰Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y⁰Is
, 4-amidino-2-fluorobenzyl and M are N; R²Is 3-aminophenyl, B is cyclohexyl, A is CH₂CH₂,
Y⁰Is 4-amidinobenzyl and M is N; R²Is 2-hydroxyphenyl, B is cyclobutyl, A is a single bond, Y⁰ Is 4-amidinobenzyl and M is N; R²Is phenyl, B is cyclobutyl, A is a single bond, Y⁰Is 4-Amidi
Nobenzyl and M are N; R²Is 3-thienyl, B is cyclobutyl, A is a single bond, Y⁰Is 4-A
Midinobenzyl and M are N; R²Is 2,6-dichlorophenyl, B is cyclobutyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is N; R²Is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are CF; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-Amidino-2-fluorobenzyl and M are CF; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-amidinobenzyl and M are CF; R²Is 3-aminophenyl, B is cyclopropyl, A is a single bond, Y⁰Is
, 4-amidino-2-fluorobenzyl and M are CF; R²Is 3-aminophenyl, B is cyclobutyl, A is a single bond, Y⁰Is
4-amidinobenzyl and M are CF; R²Is 3-aminophenyl, B is cyclobutyl, A is a single covalent bond, Y⁰Is
, 4-amidino-3-fluorobenzyl and M are CF; R²Is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y⁰Is
, 4-amidinobenzyl and M are CF; R²Is 5-amino-2-thienyl, B is cyclobutyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is CF; R²Is 3-aminophenyl, B is cyclopropyl, A is CH₂, Y⁰Is
, 4-amidinobenzyl and M are CF; R²Is 3-aminophenyl, B is 2- (2R) -bicyclo [2.2.1]-
Heptyl, A is a single bond, Y⁰Is 4-amidinobenzyl and M is CF; R²Is 3-aminophenyl, B is cyclopentyl, A is a single bond, Y⁰Is
, 4-amidino-2-fluorobenzyl and M are CF; R²Is 3-aminophenyl, B is cyclohexyl, A is CH₂CH₂,
Y⁰Is 4-amidinobenzyl and M is CF; R²Is 2-hydroxyphenyl, B is cyclobutyl, A is a single bond, Y⁰ Is 4-amidinobenzyl and M is CF; R²Is phenyl, B is cyclobutyl, A is a single bond, Y⁰Is 4-Amidi
Nobenzyl and M are CF; R²Is 3-thienyl, B is cyclobutyl, A is a single bond, Y⁰Is 4-A
Midinobenzyl and M are CF; R²Is 2,6-dichlorophenyl, B is cyclobutyl, A is a single bond, Y ⁰ Is 4-amidinobenzyl and M is CF] or the pharmaceutically acceptable salt thereof. 33. The formula:Wherein B is a compound of the formula:(Where R³², R³³, R³⁴, R³⁵And R³⁶, Independently, hydride
, Acetamide, haloacetamide, amidino, guanidino, alkylenedioxy
Si, haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino
, Alkoxyamino, haloalkanoyl, nitro, lower alkylamino, alk
Ruthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,
Alkylsulfonamide, amidesulfonyl, monoalkylamidosulfonyl, di
Alkylamidosulfonyl, alkyl, alkenyl, halo, haloalkyl, halo
Alkenyl, haloalkoxy, hydroxyalkyl, alkylamino, carbohydrate
Lucoxy, carboxy, carboxamide, cyano and Q^bSelected from the group consisting of
B is hydride, trialkylsilyl, C2-C8 alkyl, C3-C8 alkyl
Cyrenyl, C3-C8 alkenyl, C3-C8 alkynyl and C2-C8 halo
A group selected from the group consisting of alkyl, wherein each member of B is
Any carbon containing up to 6 atoms from the bond site is represented by R³², R³³, R³⁴, R ³⁵ And R³⁶May be substituted with one or more groups from the group consisting of
B comprises C3-C12 cycloalkyl and C4-C saturated heterocyclyl;
A group which may be selected from the group consisting of:³³Is replaced by
And a ring carbon other than the carbon at the binding site of B to A may be substituted with oxo.
Where more than one ring carbon is simultaneously substituted with oxo
Nevertheless, the ring carbon and nitrogen adjacent to the binding site are⁹Or R¹³Replace with
R⁹Ring carbon two atoms away from the bonding site adjacent to the^{1 0} May be substituted with¹³Ring carbon adjacent to the position and two atoms away from the binding site
The element is R¹²May be substituted with¹⁰Adjacent to the position and 3 from the binding site
The off-ring carbon is R¹¹May be substituted, 3 atoms away from the binding site
, R¹²Is adjacent to R³³May be substituted from the binding site
Atom away, R¹¹And R³³The ring carbon adjacent to the moiety is R³⁴Is replaced by
May be; R⁹, R¹⁰, R¹¹, R¹²And R¹³Are independently hydride, aceto
Amide, haloacetamide, alkoxyamino, alkanoyl, haloalkanoy
, Amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy
Si, hydroxy, amino, lower alkylamino, alkylthio, alkylsulf
Ynyl, alkylsulfamide, alkylsulfonyl, amidosulfonyl, mono
Alkylamidosulfonyl, dialkylamidosulfonyl, alkyl, halo, ha
Loalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carbohydrate
Lucoxy, carboxy, carboxyalkyl, carboxamide and cyano
A is a single covalent bond and (CH (R^Fifteen))_pa− (W⁷)_rrGroup consisting of
Wherein rr is an integer selected from 0 to 1 and pa is 0 to 3
An integer selected from and W⁷Are O, S, C (O), (R⁷) NC (O),
(R⁷) NC (S) and N (R⁷R) a group selected from the group consisting of:⁷Is a group selected from the group consisting of hydride, hydroxy and alkyl;^FifteenIs composed of hydride, hydroxy, halo, alkyl and haloalkyl.
M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, hydroxy, hydroxyamino, amidino, amino, shea
No, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoal
Kill, alkylthio, alkoxyamino, haloalkyl, haloalkoxy and
A group selected from the group consisting of halo; R²Is Z⁰A group represented by -Q; Z⁰Is a single covalent bond, (CR⁴¹R⁴²)_q, Where q is selected from 1-2
(CH (R⁴¹))_g-W⁰-(CH (R⁴²))_p,here
And g and p are each independently an integer selected from 0 to 3;⁰Is O
, S and N (R⁴¹And a group selected from the group consisting of (CH (R⁴¹)
)_e-W²²-(CH (R⁴²))_hA group selected from the group consisting of
And h are independently an integer selected from 0 to 1;²²Is CR⁴¹ = CR⁴², 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclo
Hexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclo
Pentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholini
, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1
, 3-Piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-
Piperazinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl
Dinyl, 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-te
A group selected from the group consisting of trahydrofuranyl, provided that Z⁰Is a pyrazinone
Directly attached to the ring; R⁴¹And R⁴²Is independently from hydride, hydroxy, and amino
A group selected from the group consisting of:⁰Is a single covalent bond, aryl and heteroaryl
Other groups, wherein one carbon adjacent to the carbon at the site of attachment is R⁹Is replaced by
And the other carbon adjacent to the carbon at the binding site is R¹³Has been replaced by
Well, R⁹And two carbons away from the carbon at the binding site are represented by R¹⁰Replace with
R¹³Is adjacent to and two atoms away from the carbon at the binding site,
R¹²May be substituted with¹⁰And R¹²The carbon adjacent to both is R ¹¹ K may be CHR^4aWhere R^4aIs hydride, hydroxyalkyl
, Alkyl, alkoxyalkyl, alkylthioalkyl and haloalkyl
A group selected from the group consisting of: E⁰Is a single covalent bond, C (O) N (H), (H) NC (O), (R⁷) NS (
O)₂And S (O)₂N (R⁷A group selected from the group consisting of:^ATIs Q^b−Q^sA group represented by the formula: Q^sIs (CR³⁷R³⁸)_bWhere b is an integer selected from 1 to 4,
R³⁷Is a group selected from the group consisting of hydride, alkyl and haloalkyl
, And R³⁸Is hydride, alkyl, haloalkyl, aroyl and hetero
A group selected from the group consisting of aroyl, provided that at least one aroyl or
Has a heteroaroyl substituent and is more than one aroyl or heteroaroyl
But at the same time (CR³⁷R³⁸)_bDoes not bind to the aroyl and
The above heteroaroyl has one to three ring carbons represented by R¹⁶, R¹⁷, R¹⁸and
R¹⁹May be substituted with a substituent selected from the group consisting of
And the above heteroaroyls are CR³⁷R³⁸And directly to E⁰Joined to
And more than one alkyl or haloalkyl is simultaneously CR³⁷R³⁸Tied to
And the alkyl and haloalkyl are aroyl or heloalkyl.
Binds to a carbon other than the bond to the teloaroyl; R¹⁶, R¹⁷, R¹⁸And R¹⁹Are, independently, hydride, amidino,
Anidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
Alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl
, Alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, ha
Loalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl and shea
A group selected from the group consisting of¹⁶And R¹⁹Is Q^bWhere R¹⁶And R¹⁹of
More than one is Q^bIs not; Q^bIs NR²⁰R²¹, Q^be, Where Q^beIs a hydride and N (R ²⁶ ) C (NR²⁵) N (R²³) (R²⁴) And C (NR²⁵) NR²³R ²⁴ A group selected from the group consisting of:²⁰And R²¹More than one
Are simultaneously hydroxy, amino, alkylamino or dialkylamino
And R²³And R²⁴More than one is simultaneously
Cannot be amino, alkyl, amino or dialkylamino; R²⁰, R²¹, R²³, R²⁴, R²⁵And R²⁶The independently, hydrangea
, Alkyl, hydroxy, amino, alkylamino and dialkylamino
Or a pharmaceutically acceptable salt thereof. 34. The formula:[Wherein B is a compound of the formula:(Where R³², R³³, R³⁴, R³⁵And R³⁶, Independently, hydride
, Amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy,
Amino, N-methylamino, dimethylamino, methylthio, ethylthio, trif
Fluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, full
Oro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydr
Roxymethyl, amidocarbonyl, carboxy, cyano and Q^bGroup consisting of
B is hydride, ethyl, 2-propenyl, 2-propynyl, propyl, iso-
Propyl, 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-pentenyl
2-methylbutyl, 2-methyl-2-butenyl, 3-methylbutyl, 3-methyl
Tyl-2-butenyl, 1-hexyl, 2-hexenyl, 4-hexenyl, 2-hexyl
Xynyl, 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-hep
Tyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 2
-Heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptinyl
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-pe
Inthinyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl, 4
-Trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoro
Methylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,3
A group which may be selected from the group consisting of:
Each member has any carbon containing up to 5 atoms from the site of attachment of B to A ³² , R³³, R³⁴, R³⁵And R³⁶One or more of the group consisting of
B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexyl,
Cloheptyl, 2- (2R) -bicyclo [2.2.1] -heptyl, oxetane-
3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-i
And bicyclo [3.1.0] hexan-6-yl
Good groups wherein each ring carbon is R³³May be substituted at the binding site
The ring carbon and nitrogen adjacent to the carbon are R⁹Or R¹³May be replaced by
, R⁹Ring carbon two atoms away from the carbon at the site of attachment is R¹⁰Replaced by
May be R¹³Ring carbon adjacent to the position and two atoms away from the carbon at the binding site
, R¹²May be substituted; R⁹, R¹¹, And R¹³Is independently hydride, methyl, ethyl, meth
Xy, ethoxy, hydroxy, amino, N-methylamino, N, N-dimethyla
Mino, methylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-
Trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methyl
Luamidosulfonyl, N, N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, cal
A group selected from the group consisting of boxy and cyano; R¹⁰And R¹²Is independently hydride, amidino, amide carbonyl,
N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy
, Hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy
Chill, carboxy, carboxymethyl, amino, acetamido, trifluorome
Chill, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoro
Acetamide, aminomethyl, N-methylamino, dimethylamino, amide sulf
Phonyl, N-methylamidosulfonyl, N, N-dimethylamidosulfonyl,
Selected from the group consisting of toxic, fluoro, chloro, bromo and cyano
A is a single covalent bond, NH, N (CH₃), CH₂, CH₃CH, CH₂CH₂ And CH₂CH₂CH₂A group selected from the group consisting of: M is N and R¹A group selected from the group consisting of: -C; R¹Is hydride, hydroxy, amino, amidino, hydroxyamino,
Nomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl
, Ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Oroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydro
Xyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy
, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro and bromo
A group selected from the group consisting of: R²Is phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazo
Yl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl and 3-pyridyl
A group selected from the group consisting of: wherein one carbon adjacent to the carbon at the binding site is
, R⁹And the other carbon adjacent to the carbon at the bonding site is R¹³ May be substituted with⁹Adjacent to and two atoms away from the carbon at the binding site
Is R¹⁰May be substituted with¹³, And two atoms from the carbon at the binding site
The separated carbon is R¹²May be substituted with¹⁰And R¹²Next to both
The carbon in contact is R¹¹May be substituted; Y^ATIs Q^b−Q^s; Q^sIs: C [R³⁷(Benzoyl)] (CR³⁷R³⁸)_b], C [R³⁷(2-pyridylcarbonyl])] (CR³⁷R³⁸)_b], C [R³⁷(3-pyridylcarbonyl])] (CR³⁷R³⁸)_b], C [R³⁷(4-pyridylcarbonyl])] (CR³⁷R³⁸)_b], C [R³⁷(2-thienylcarbonyl])] (CR³⁷R³⁸)_b], C [R³⁷(3-thienylcarbonyl])] (CR³⁷R³⁸)_b], C [R³⁷(2-thiazoylcarbonyl])] (CR³⁷R³⁸)_b], C [R³⁷(4-thiazoylcarbonyl])] (CR³⁷R³⁸)_b], And C [R³⁷(5-thiazoylcarbonyl])] (CR³⁷R³⁸)_bGroup consisting of
Where b is an integer selected from 1-3, R³⁷And R^{3 8} Is independently selected from the group consisting of hydride, alkyl, and haloalkyl
Wherein the aroyl and the heteroaroyl are 1 to 3 ring carbons
Element is R¹⁶, R¹⁷, R¹⁸And R¹⁹A substituent selected from the group consisting of
Optionally substituted, provided that R¹⁷And R¹⁸Is a benzoyl substituent and
Meta and para carbons for the carbonyl of phenyl and heteroaroyl substituents
The benzoyl and the heteroaroyl may be substituted by a selected carbon.
Is bonded to the carbon directly bonded to the amide nitrogen of the 1- (amidocarbonylmethylene) group.
Together, more than one alkyl or heteroalkyl is simultaneously CR³⁷R³⁸ Does not bind to R¹⁶, R¹⁷, R¹⁸And R¹⁹Is independently hydride, methyl, ethi
, Amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1
-Aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, methyl
Luthio, ethylthio, trifluoromethylthio, methylsulfinyl, methyls
Ruphonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoro
Oroethyl, trifluoromethoxy, fluoro, chloro, amidosulfonyl, N
-Consisting of methylamidosulfonyl, hydroxymethyl, carbonyl and cyano
A group selected from the group consisting of^bIs NR²⁰R²¹, And C (NR²⁵) NR²³R²⁴Group consisting of
Group selected from the above, provided that Q^bThe group is directly attached to the carbon atom;²⁰, R²¹, R²³, R²⁴And R²⁵Are, independently, hydride, al
Or a pharmaceutically acceptable salt thereof, which is a group selected from the group consisting of kill and ethyl. 35. B is 2-aminophenyl, 3-aminophenyl, 3-a
Midinophenyl, 4-amidinophenyl, 3-carboxyphenyl, 3-carbo
Xy-5-hydroxyphenyl, 3-chlorophenyl, 4-chlorophenyl, 3
, 4-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 3,
4-difluorophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl,
3-methoxyaminophenyl, 3-methoxyphenyl, 4-methoxyphenyl,
3-methylphenyl, 4-methylphenyl, phenyl and 3-trifluoromethyl
A group selected from the group consisting of tylphenyl; B is hydride, ethyl, 2-propenyl, 2-propynyl, propyl, iso-
Propyl, butyl, 2-butyl, (R) -2-butyl, (S) -2-butyl, t
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-di
Methylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydr
Roxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinop
Ropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybuty
, 6-cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl, 2-
Methylbutyl, (S) -2-methylbutyl, 3-aminopropyl, 2-hexyl
And B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2
-(2R) -bicyclo [2.2.1] -heptyl, oxetan-3-yl, azeti
Group consisting of gin-1-yl, azetidin-2-yl and azetidin-3-yl
A is a single covalent bond, CH₂, CH₃CH, CH₂CH₂And CH₂CH₂C
H₂A group selected from the group consisting of: M is N and R¹A group selected from the group consisting of: -C; R¹But hydride, hydroxy, amino, amidino, hydroxyamino,
Nomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,
Droxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro
A group selected from the group consisting of b and chloro; R²Is 5-amino-3-amidocarbonylphenyl, 5-amino-2-fur
Orophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-
Methoxycarbonylphenyl, 3-amidinophenyl, 3-amino-2-methyl
Phenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, benzyl
, 3-carboxyphenyl, 3-carboxy-5-aminophenyl, 3-cal
Boxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl
3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylfe
Nyl, 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-methoxy
Phenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxy
Carbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl,
2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3
-Trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-
Trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thi
Enyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl
Y or a group selected from the group consisting of 3-thienyl; Y^ATBut Q^b−Q^sA group represented by the formula: Q^sIs: [CH (benzyl)] (CH₂)_b, [CH (2-pyridylcarbonyl)] (CH₂ )_b, [CH (3-pyridylcarbonyl)] (CH₂)_b, [CH (4-pyridyl
Carbonyl)] (CH₂)_b, [CH (2-thienylcarbonyl)] (CH₂)_b
, [CH (3-thienylcarbonyl)] (CH₂)_b, [CH (2-thiazol dolphin
Rubonyl)] (CH₂)_b, [CH (4-thiazoylcarbonyl)] (CH₂)_b
And [CH (5-thiazoylcarbonyl)] (CH₂)_bSelected from the group consisting of
Wherein b is an integer selected from 1 to 3, provided that aroyl and
And the above heteroaroyl has 1 to 3 ring carbons and R¹⁶, R¹⁷, R¹⁸And
And R¹⁹May be substituted with a substituent selected from the group consisting of ¹⁷ And R¹⁸Is the carbonyl of benzoyl and heteroaroyl substituents.
May be substituted with carbons selected from meta and para carbons other than
, The benzoyl and the heteroaroyl are 1- (amidocarbonylmethyl
D) a carbon attached directly to the amide nitrogen of the group;¹⁶And R¹⁹But independently, hydride, amidino, amino, aminomethy
Methoxy, methylamino, hydroxy, hydroxymethyl, fluoro,
A group selected from the group consisting of b and cyano; R¹⁷And R¹⁸But independently hydride, fluoro, chloro, hydroxy
Selected from the group consisting of, hydroxymethyl, amino, carboxy and cyano
Group; Q^bIs C (NR²⁵) NR²³R²⁴A group represented by R²³, R²⁴And R²⁵Is independently the group consisting of hydride and methyl
35. The compound according to claim 34, which is a group selected from: or a pharmaceutically acceptable salt thereof. 36. B is 3-aminophenyl, 3-amidinophenyl, 4-
A group selected from the group consisting of amidinophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 4-methylphenyl and phenyl; B is hydride, ethyl, 2-propenyl, 2- Propynyl, propyl, isopropyl, butyl, 2-butyl, (R) -2-butyl, (S) -2-butyl, t
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-
A group which may be selected from the group consisting of methylbutyl, (S) -2-methylbutyl, 3-aminopropyl, 2-hexyl and 4-aminobutyl; B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
A group which may be selected from the group consisting of-(2R) -bicyclo [2.2.1] -heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl and azetidin-3-yl; A is a single covalent bond, a group selected from the group consisting of CH ₂ , CH ₂ CH ₂ and CH ₂ CH ₂ CH ₂ ; M is a group selected from the group consisting of N and R ¹ -C; R ¹ Is a group selected from the group consisting of hydride, 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-methanesulfonylamino-phenyl, 3-methoxycarbonylphenyl, 3-dimethylaminophenyl, 3-methylamino-phenyl, 2-
Methylphenyl, 3-methylphenyl, phenyl, 3-pyridyl, 3-trifluoroacetamidophenyl, 3-bromo-2-thienyl, 2-thienyl and 3
- group is selected from the group consisting of thienyl; ^{Y AT} is 5-guanidino-1-oxo-1- (2-thiazolyl) -2-phenyl-5-guanidino-1-oxo-1- (4-thiazolyl) -2-pentyl,
5-guanidino-1-oxo-1- (5-thiazolyl) -2-pentyl, 5-guanidino-1-oxo-1- (4-amino-2-thiazolyl) -2-pentyl and 5-guanidino-1- 36. The compound according to claim 35, which is a group selected from the group consisting of oxo-1-phenyl-2-pentyl; or a pharmaceutically acceptable salt thereof. 37. The formula: embedded image [Wherein, R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , ^YAT 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-thiazoyl) -2-pentyl and M are C
H; R ² is benzyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazoyl) -2-pentyl and M is C
H; ^{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 C
H; R ² is benzyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazoyl) -2-pentyl and M is C
H; ^{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 C
H; R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , and ^YAT 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-thiazoyl) -2-pentyl and M are C
F; ^{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 C
F; ^{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 C
F; ^{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 C
F; ^{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 C
F; R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , and ^YAT is 5
- guanidino-1-oxo-1- (2-thiazolyl) -2-pentyl, and M is CCl; ^{R 2} is phenyl, B is phenyl, A ^_is, CH ₂ CH _2, ^{Y AT} is 5-guanidino -1-oxo-1- (2-thiazoyl) -2-pentyl and M are C
Cl; ^{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 C
Cl; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazoyl) -2-pentyl and M is C
Cl; ^{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 C
Cl; R ² is phenyl, B is phenyl, A is CH ₂ CH ₂ , Y ^AT is 5-guanidino-1-oxo-1- (2-thiazoyl) -2-pentyl and M is C
Cl; R ² is 3-aminophenyl, B is phenyl, A is CH ₂ , ^YAT 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-thiazoyl) -2-pentyl and M are 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
34. The compound according to claim 33, which is selected from the group represented by: or a pharmaceutically acceptable salt thereof. 38. A composition for inhibiting a thrombotic state in blood, comprising a compound according to any one of claims 8, 16, 24, 32 and 37 and a pharmaceutically acceptable carrier. 39. The 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 pharmaceutically acceptable carrier. , A composition that inhibits thrombotic conditions in blood. 40. A method for inhibiting a thrombotic condition in blood, which comprises administering a therapeutically effective amount of the composition according to any one of claims 38 and 39 to blood. 41. A method of inhibiting platelet aggregate formation in blood, comprising administering to the blood a therapeutically effective amount of the composition of any one of claims 38 and 39. 42. A method for inhibiting thrombus formation in blood, comprising administering to the blood a therapeutically effective amount of the composition of any one of claims 38 and 39. 43. A method for 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 any one of claims 38 and 39. . 44. A method for treating or preventing deep vein thrombosis in a mammal, comprising administering to the mammal a therapeutically effective amount of the composition of any one of claims 38 and 39. 45. A method for treating or preventing cardiogenic thromboembolism in a mammal, comprising administering to the mammal a therapeutically effective amount of the composition according to any one of claims 38 and 39. 46. A method for treating or preventing thrombo-occlusive attacks in humans and other mammals, comprising administering to the mammal a therapeutically effective amount of the composition of any one of claims 38 and 39. 47. Thrombosis associated with cancer and cancer chemotherapy in humans and other mammals, characterized in that a therapeutically effective amount of the composition according to any one of claims 38 and 39 is administered to the mammal. Treatment or prevention method. 48. A method for treating or preventing unstable angina in humans and other mammals, comprising administering to the mammal a therapeutically effective amount of the composition of any one of claims 38 and 39. 49. A method for inhibiting thrombus formation in blood, comprising administering a therapeutically effective amount of a fibrinogen receptor antagonist and a compound according to any one of claims 1 to 37 to blood. 50. A method of inhibiting thrombus formation or treating thrombus formation in a mammal,
Or use of a compound according to any one of claims 1 to 37 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for preventing thrombus formation.