WO1999040092A1

WO1999040092A1 - Oxo-dipyridoimidazole-carboxamides: gaba brain receptor ligands

Info

Publication number: WO1999040092A1
Application number: PCT/US1999/001688
Authority: WO
Inventors: Linghong Xie; Kevin S. Currie; Pamela Albaugh; Kenneth Shaw; Alan J. Hutchison
Original assignee: Neurogen Corporation
Priority date: 1998-02-04
Filing date: 1999-02-04
Publication date: 1999-08-12
Also published as: AU2653499A

Abstract

Disclosed are compounds of formula (I) or pharmaceutically acceptable non-toxic salts thereof wherein: (a) represents an optionally substituted nitrogen-containing ring system; R is defined herein; and G is an organic or inorganic group, which compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors, and are therefore useful in the diagnosis and treatment of anxiety, Down Syndrome, sleep, cognitive and seizure disorders, depression, overdose with benzodiazepine drugs and for enhancement of alertness.

Description

Oxo-dipyridoi idazole-carboxamides : GABA Brain Receptor Ligands

BACKGROUND OF THE INVENTION

Field of the Invention

This invention relates to substituted oxo- dipyridoimidazole-carboxamides which selectively bind to GABAa receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in enhancing alertness and treating anxiety, overdoses of benzodiazepine-type drugs, Down Syndrome, depression, and sleep, seizure and cognitive disorders.

Description of the Related Art

γ-Aminobutyric acid (GABA) is regarded as one of the major inhibitory amino acid transmitters in the mammalian brain. Over 40 years have elapsed since its presence in the brain was demonstrated (Roberts & Frankel, J. Biol. Chem. 187 : 55-63, 1950; Udenfriend, J. Biol. Chem. 18 : 65-69, 1950). Since that time, an enormous of effort has been devoted to implicating GABA in the etiology of seizure disorders, sleep, anxiety and cognition (Tallman and Gallager, Ann. Rev. Neuroscience 8.: 21- 44, 1985) . Widely, although unequally, distributed through the mammalian brain, GABA is said to be a transmitter at approximately 30% of the synapses in the brain. GABA mediates many of its actions through a complex of proteins localized both on cell bodies and nerve endings; these are called GABAa receptors. Postsynaptic responses to GABA are mediated through alterations in chloride conductance that generally, although not invariably, lead to hyperpolarization of the cell. Drugs that interact at the GABAa receptor can possess a spectrum of pharmacological activities depending on their abilities to modify the action of GABA.

The 1,4-Benzodiazepines, such as diazepam, continue to be among the most widely used drugs in the world as anxiolytics, sedative-hypnotics, muscle relaxants, and anticonvulsants . A number of these compounds are extremely potent drugs; such potency indicates a site of action with a high affinity and specificity for individual receptors. Early electrophysiological studies indicated that a major action of benzodiazepines was enhancement of GABAergic inhibition. Recently, those compounds possessing activity similar to the benzodiazepines are called agonists. Compounds possessing activity opposite to benzodiazepines are called inverse agonists, and the compounds blocking both types of activity have been termed antagonists.

The GABAa receptor subunits have been cloned from bovine and human cDNA libraries. A number of distinct cDNAs were identified as subunits of the GABAa receptor complex by

cloning and expression. These are categorized into α, β, γ, δ,

ε, and provide a molecular basis for the GABAa receptor heterogeneity and distinctive regional pharmacology. The γ subunit appears to enable drugs like benzodiazepines to modify the GABA responses. The presence of low Hill coefficients in the binding of ligands to the GABAa receptor indicates unique profiles of subtype specific pharmacological action.

With the discovery of the "receptor" for the benzodiazepines and the subsequent definition of the nature of the interaction between GABA and the benzodiazepines, it appears that the behaviorally important interactions of the benzodiazepines with different neurotransmitter systems are due in a large part to the enhanced ability of GABA itself to modify these systems. Each modified system, in turn, may be associated with the expression of a behavior. Depending on the mode of interaction, these compounds are capable of producing a spectrum of activities (either sedative, anxiolytic, and anticonvulsant , or wakefulness, seizures, and anxiety) .

U.S. Patent No. 5,639,760, PCT publication WO 94/04532, Bioorg. Med. Chem. Lett. 1996, 6. (3), 333-338, and J. Med. Chem. 1995, 3_8. (1), 16-20 discloses various 3-oxo-pyrido [1, 2- a] -benzimidazole-4 -carboxyl and 4-oxo-azepino [1, 2-a] -benz- imidazole-5-carboxyl derivatives.

-3* SUMMARY OF THE INVENTION

This invention provides novel compounds of Formula II which interact with a GABAa binding site, the benzodiazepine receptor. The invention provides pharmaceutical compositions comprising compounds of Formula I. The invention also provides compounds useful in the diagnosis and treatment of anxiety, Down Syndrome, depression, sleep, cognitive and seizure disorders, and overdose with benzodiazepine drugs and for enhancement of alertness. Accordingly, a broad embodiment of the invention is directed to compounds of Formula I :

or the pharmaceutically acceptable non-toxic salts thereof wherein:

<* represents a nitrogen-containing ring system which is optionally substituted with up to two groups independently selected from halogen, or R³R⁴N- ; R²OY- wherein Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or Cι-C₆ alkoxy or Cι-C₆ alkyl, each of which is optionally substituted on its alkyl portion with - NR³R⁴ , where

R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; or R³ and R⁴ together with the nitrogen to which they are attached form a 3-7 membered ring;

G is

C₃-C₇ cycloalkyl, C_x-C_& alkyl optionally substituted with

Cx-Cβ alkoxy, or mono- or di (C-_L-Cβ) alkylamino; or a group of the formula:

(W)n ^R¹ where

R¹ is Cι-C₆ alkyl or C₃-C₇ cycloalkyl ; a group of the formula :

where s is 1 or 2; and R , Rm and Rn independently represent halogen, hydroxy,

-5* trifluoromethyl, or Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (C-*_.-C₆) alkylamino; or R¹ is aryl or heteroaryl, each of which is optionally substituted with up to three groups independently selected from halogen, hydroxy, trifluoromethyl, or mono- or di (Ci-Cβ) alkylamino; ROY- wherein Y and R² are defined as above, and Y and R², when R² is not hydrogen, are independently optionally substituted with -

NR³R⁴; or Cι-C₆ alkyl or Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with a heterocyclic group or -NR³R⁴ where R³ and R⁴ are as defined above; or Y may be linked through R³ or R⁴ to form a heterocyclic ring; W represents CR⁵R⁶ where

R⁵ and R⁶ independently represent hydrogen, Cχ-C₆ alkyl, C₃-C₇ cycloalkyl, or

CR⁵R⁶forms a C₃-C₇ cycloalkyl group; and n is 0, or an integer of from 1-4; and R represents hydrogen, C*-.-C₆ alkyl, or C₃-C₇ cycloalkyl; or arylalkyl or heteroarylalkyl where each aryl portion is optionally substituted with up to three groups

-6- independently selected from halogen, hydroxy, trifluoromethyl, or mono- or di (Cι-C₆) alkylamino; R²OY- where R² and Y are defined as above, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or

Cι-C₆ alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴ where R³ and R⁴ are as defined above, or a heterocyclic group.

These compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors . These compounds are useful in the diagnosis and treatment of anxiety, Down Syndrome, depression, sleep, cognitive and seizure disorders, overdose with benzodiazepine drugs and for enhancement of alertness .

Thus, the invention also provides methods and compositions for treating and diagnosing anxiety, Down Syndrome, depression, sleep, cognitive and seizure disorders, and overdose with benzodiazepine drugs.

In another aspect, the invention encompasses compounds that are intermediates in the synthesis of the compounds of Formula I . DETAILED DESCRIPTION OF THE INVENTION

The novel compounds encompassed by the invention can be described by the general Formula I set forth above or the pharmaceutically acceptable non-toxic salts thereof. Preferred compounds of Formula I are those where:

N I

represents pyrido or tetrahydropyrido systems. Still other preferred compounds of Formula I include those where G is phenyl, phenyl (C**_.-C₃) alkyl , e.g., benzyl, or pyridyl, where the aromatic ring portion of each is optionally substituted with halogen, (C-*_.-C₆) alkyl , (Cι-C₆) alkoxy.

Other preferred compounds of Formula I are those where G is phenyl, benzyl, or pyridyl, where the aromatic ring portion of each is substituted with one or two halogens and/or mono- or di (Cι-C₆) alkylamino (Cι-C₆) alkyl, or mono- or di (Ci- C₆) alkylamino (C!-C₆) alkoxy. The dialkylamino groups on the G phenyl, benzyl, and pyridyl groups include nitrogen-containing heterocycles such as, for example, piperazine, piperidine, morpholine, pyrrolidine, and 1, 2 , 3 , 4-tetrahydropyridine moieties.

In addition to the compounds of Formula I, the invention encompasses compounds of Formula II

II wherein:

Zi, Z₂, Z₃, and Z₄ independently represent N or CR⁷, with the proviso that at least one but not more than two of Z**., Z₂, Z₃, and Z₄ represent nitrogen;

R is as defined above for Formula I; R⁷ is hydrogen, halogen, R³R⁴N- , R²OY- wherein Y is C-_L-Cg alkylene and R² represents hydrogen, ι -C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently

optionally substituted with -NR³R⁴; or

Cι-C₆ alkoxy or C_x-C₆ alkyl, each of which is optionally substituted on its alkyl portion with -

NR³R⁴, alkyl, alkoxy, R³R⁴NY- , or R³R⁴N- , where

Y is as defined above for Formula II; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; or

R³ and R⁴ may be taken together to form a ring. Preferred compounds of Formula II are those where Z_i; Z₂, or Z₄ is nitrogen, R is C-*_.-C₃ alkyl, mono- or di (C**_.-

C₆) alkylamino (Cι-C₆) alkyl, or mono- or di (C-*.-C₃) alkylamino (C**_.- C₆) alkoxy.

In Formula II above, G represents (i) (C₃-C₇) cycloalkyl,

(ii) a group of the formula:

^RVY where Y is Cχ-Cg alkylene; and R⁸ is hydrogen, lower alkyl, or (C₃-C₇) cycloalkyl,

(iii) a group of the formula:

V^N where

Y is as defined above for ii ; and

R⁹ and R¹⁰ are same or different and represent hydrogen, Cι-C₆ alkyl , C₃-C₇ cycloalkyl , Cι-C₃ alkylamino (Cι-C₆) alkyl , or Cι-C₆ alkoxy (C**_.-C₆) alkyl ; or

R⁹ and R¹⁰ together with the nitrogen atom to which they are attached form a heterocyclic moiety of 5, 6, or 7 members such as imidazolyl,

-10- pyrrolidinyl, morpholinyl, N-unsubstituted or N- (C**_.- C₆) alkyl piperazinyl, or piperidinyl ;

(iv) a group of the formula

R¹¹

where

R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², -NR³R⁴; R¹², R^12', and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl ,

NR³R⁴ ; R²0Y- wherein Y is C_x-Cg alkylene and R² represents hydrogen, Ci-Cg alkyl , or C₃ -C₇ cycloalkyl , and Y and R² , when R² is not hydrogen, are independently optionally substituted with NR³R⁴ ; Ci-Cg alkoxy or Cι-C₆ alkyl , or C₃ -C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴ ; or

- 11 - R¹¹ and R¹², or R¹² and R¹³ together with the atoms to which they are attached form an aryl, heteroaryl, or (hetero) cyclic ring; or or Y may be linked through R³ or R⁴ to form a heterocyclic ring; where R², R³, R⁴, Y, R⁹, and R¹⁰ are defined as above ;

(v) a group of the formula:

where Y, R¹¹ and R¹¹ are defined above;

where Y, R , R , R , and R are as defined above;

(vii) a group of the formula:

R¹¹

^■12* where Y, R⁹, R¹⁰, R¹¹, R^11' , and R¹³ are as defined above ;

(viii) a group of the formula:

NR⁹R¹⁰

where Y, R⁹, R¹⁰, R¹¹, R^11' , and R¹³ are as defined above;

( ix) a group of the formula :

R 11

R 12

.Yv

_R -1_l NR ι9^ιR-,1¹0

where Y, R⁹, R¹⁰, R¹¹, R^11' , and R¹² are as defined above ; (x) a group of the formula:

~ 0

/ y NR⁹R 1

where each Y, and R⁹, R¹⁰, R¹¹, R^11' , and R¹² are as defined above ;

(xi) a group of the formula:

-13- γ< .NR⁹R¹⁰

where each Y, R⁹, R¹⁰, R¹¹, R^11' , and R¹² are as defined above ;

(xii) a group of the formula:

where R¹¹, R¹², and R¹³ are as defined above respectively, and

R¹⁴, R¹⁵, R¹⁶, and R¹⁷ independently carry the definitions for R¹² and R¹³;

(xiii) a group of the formula:

R^1f R¹⁴

where R¹¹, R^11' , R¹², R¹⁴, R¹⁵, R¹⁶, and R¹⁷ are as defined above respectively;

•14* (xiv) a group of the formula:

R^fc

where X is (C₃-C₇) cycloalkyl, and R⁵ and R⁶ are as defined above;

(xv) a group of the formula:

where R⁵, R⁶, R¹¹, R^11' , R¹², R^12' , and R¹³ are as defined above respectively;

(xvi) a group of the formula:

where Y, R⁵, R⁶, R⁹, R¹⁰, and R¹¹ are as defined above respectively;

(xvii) a group of the formula:

•15-

where R⁵, R⁶, R¹¹, R⁸, and Y are as defined above respectively;

(xviii) a group of the formula:

R⁵ R 11

where R⁵, R^s, R¹¹, R^11', R¹³, R⁸, and Y are as defined above respectively;

(xix) a group of the formula:

R^£

where R⁵, R⁶, R¹¹, R¹², R⁸, and Y are as defined above respectively;

(xx) a group of the formula:

R⁵ R¹¹ _R9_R10

^■ 16 - where R⁵, R⁶, R⁹, R¹⁰, R¹¹, R^11' , R¹³, and Y are as defined above respectively;

(xxi) a group of the formula:

NR⁹R 10

where R⁵, R⁶, R⁹, R¹⁰, R¹¹, R¹², and Y are as defined above respectively;

(xxii) a group of the formula:

⁹R¹⁰RN

/ Y

R⁵ R⁶

where R⁵, R⁶, R⁹, R¹⁰, R^11' , R¹², R¹³, and Y are as defined above respectively;

(xxiii) a group of the formula:

R⁵ R⁶ R 11

NR⁹R¹⁰

where R¹¹ , R¹² , R^{12 '} , and R¹³ are as def ined above respectively;

^■ 17 - (xxiv) a group of the formula:

R⁵R⁶ R 11

R

NR⁹R¹⁰

where R⁵, R⁶, R⁹, R¹⁰, R¹¹, R^11' R , and Y are as defined above respectively;

(xxv) a group of the formula :

where R¹¹, R¹², R^12' , and R¹³ are as defined above respectively;

(xxvi) a group of the formula:

6 F t^1T

R x^R I X R¹⁵

1 ?

Rⁿ ^ _Rl6

R 1 Λ2Δ R 017

where R³, R^b, R¹ , R , R^x% R^x\ R¹⁵, R^Xb, and R ^■>17^/ are as defined above,

(xxvii) a group of the formula:

-18-

where R⁵, R⁶, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, and R¹⁷ are as defined above respectively;

(xxviii) a group of the formula:

^l Q

where Q represents a heteroaryl group;

(xxix) a group of the formula:

& where R , R and Q are as defined above; and

(xxx) a group of the formula:

where Y, R¹¹, R^11' , R¹², R^12' and R¹³ are as described above .

^■19- The invention also encompasses compounds of Formula lib

, ^R <λ .G

^■N H

Z -

^:O

lib wherein:

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Zi, Z_2/ Z₃, and Z₄ represents NR¹⁸;

R, R⁷ and G are as defined above for Formula Ila; and

R¹⁸ is (Ci-Cg) alkyl, (C₃-C₇) cycloalkyl, or benzyl.

Thus, the present invention encompasses compounds of the following formulae:

τf

III where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Zi, Z₂,

Z₃, and Z₄ represents NR¹⁸; X is (C3-C7) cycloalkyl; and

R, R¹⁸, and R⁷ are as defined above.

-20- C Y—OR⁸

IV

where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z_{l t} Z₂, Z₃, and Z₄ represents NR¹⁸; and

R, R¹⁸, Y, R⁸, and R⁷ are as defined above.

/^R O _/Y__NR9_R10 i V-NH

"3\^

V where

Z_x, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z , Z₂ , Z₃, and Z₄ represents NR¹⁸;

R, R¹⁸, Y, R⁹, R¹⁰, and R⁷ are as defined above.

^■21-

-N _R11 H

^:O

VI where

Zi, Z_2/ Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Zi, Z₂, Z₃, and Z represents NR¹⁸;

R, R¹⁸, R¹¹, R^11', R¹², R^12', R¹³, and R⁷ are as defined above .

I^* -*^

VII where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Zi, Z₂, Z₃, and Z₄ represents NR¹⁸; R, R¹⁸, R¹¹, R^11', Y, and R⁷ are as defined above.

^■22- R31'2^~

VIII where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z_1# Z₂, Z₃, and Z₄ represents NR¹⁸;

R, R ,18 , Ril^xl^x, R ,12 Y, RA R^xu, and R' are as defined above.

IX where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z**_., Z₂, Z₃, and Z represents NR¹⁸; R, R¹⁸, R¹¹, R^11', R¹³, Y, R⁹, R¹⁰, and R⁷ are as defined above .

-23*

X where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z**_., Z₂, Z₃, and Z₄ represents NR¹⁸;

R, R¹⁸, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, and R⁷ are as defined above.

XI where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z_x , Z₂, Z₃, and Z₄ represents NR¹⁸;

R, R¹⁸, R¹¹, R¹², R^11', R¹⁴, R¹⁵, R¹⁶, R¹⁷, and R⁷ are as defined above.

-24-

XII where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z-*., Z₂, Z_3/ and Z₄ represents NR¹⁸;

R, R¹⁸, R⁵, R⁶, X, and R⁷ are as defined above.

R11

R12

R12'

XIII where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Zi, Z₂, Z₃, and Z₄ represents NR¹⁸;

R, R¹⁸, R¹¹, R¹², R^11', R^12', R¹³, R^s, R⁶, and R⁷ are as defined above.

-25* -NR⁹R10

XIV where

R, R¹⁸, R¹¹, R⁹, R¹⁰, Y, R⁵, R⁶, and R⁷ are as defined above.

XV where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z_λ , Z₂, Z₃, and Z represents NR¹⁸;

R, R¹⁸, R¹¹, R^11', R¹³, R⁹, R¹⁰, Y, R⁵, R^s, and R⁷ are as defined above.

-26-

XVI where

Z_x, Z₂, Z_3/ and Z₄ independently represent N or CR⁷, with the proviso that at least one but not more than two of Z_{l t} Z₂, Z₃, and Z₄ represents nitrogen;

R, R¹¹, R¹², R⁹, R¹⁰, Y, R⁵, R⁶, and R⁷ are as defined above.

In a preferred embodiment, Z-*_. in Formula XVI is nitrogen. In another preferred embodiment of the invention, Z₂ in Formula XVI is nitrogen. In yet another preferred embodiment of the invention, Z₄ is nitrogen.

XVII where

Zi, Z_2/ Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z_1# Z₂, Z₃, and Z₄ represents NR¹⁸;

R, R¹⁸, R¹¹, R⁸, Y, R⁵, R⁶, and R⁷ are as defined above.

^■27* In a preferred embodiment, Z_λ in Formula XVI is nitrogen. In another preferred embodiment of the invention, Z₂ in Formula XVI is nitrogen. In yet another preferred embodiment of the invention, Z₄ is nitrogen.

XVIII where

Zi, Z₂, Z_3/ and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z**_., Z₂, Z₃, and Z₄ represents NR¹⁸;

R, R¹⁸, R¹¹, R^11', R¹³, R⁸, Y, R⁵, R⁶, and R⁷ are as defined above .

XIX where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z_{l r} Z₂, Z₃, and Z₄ represents NR¹⁸;

-28- R, R , R^x , R , R°, Y, R% R^b, and R' are as defined above.

z^f X

$

XX where

Z_1; Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Zi, Z₂, Z₃, and Z₄ represents NR¹⁸;

R, R¹⁸, R¹¹, R¹², R¹³, R^12', R⁵, R⁶, and R⁷ are as defined above .

XXI where

Z-_L, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Zi, Z₂, Z₃, and Z represents NR¹⁸;

R, R¹⁸, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R⁵, R⁶, and R⁷ are as defined above.

^•29-

XXII where

R, R¹⁸, R¹¹, R¹², R^11', R¹⁴, R¹⁵, R¹⁶, R¹⁷, R⁵ , R⁶ , and R⁷ are as defined above.

XXIII where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Zi, Z₂, Z₃, and Z₄ represents NR¹⁸; R, R¹⁸, and R⁷ are as defined above; and

Q is heteroaryl .

R⁶

-K V-

Q

-3\₇

^'Nv °

^■30- XXIV where

Zx, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z_1; Z₂, Z₃, and Z₄ represents NR¹⁸;

R, R¹⁸, R⁵, R⁶, and R⁷ are as defined above; and

Q is heteroaryl .

XXV where

Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷, with the proviso that at least one but not more than two of Z-*_., Z₂, Z₃, and Z₄ represents NR¹⁸;

R, R¹⁸, Y, R¹¹, R¹², R¹³, R^11', R^12', and R⁷ are as defined above.

The present invention also encompasses compounds of the following formulae:

R

XXVI

-31- where R⁷, R, and G are defined above. Preferred compounds of Formula XXVI are those where : R represents

R²OY- where Y is C-*_.-C₆ alkylene and R² represents hydrogen, Ci-Cg alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or

Ci-Cg alkyl, Ci-Cg alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; and G represents a group of Formula XXVI-1:

R¹² _R13

«- - -*(£A)^q R^1V

XXVI-1 wherein

A is methylene substituted with R⁵R⁶, where R⁵ and R⁶ independently represent hydrogen or Cι-C₆ alkyl; q is 0 or an integer of from 1-3;

R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, C_ι-C_β alkyl, -OR², -

NR³R⁴ ; R¹², R^12' , and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl , -NR³R⁴;

-32- R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-Cg alkoxy or Ci-Cg alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

R¹¹ and R¹², or R¹² and R¹³ together with the atoms to which they are attached form an aryl, heteroaryl, or

(hetero) cyclic ring; or

Y and R³ or R⁴ together form a 5, 6, or 7-membered heterocyclic ring with one of the alkyl groups of

NR³R⁴ ;

Y is Ci-Cg alkylene and R² represents hydrogen, Cχ-Cg alkyl , or C₃-C₇ cycloalkyl ; and R³ and R⁴ are the same or different and represent hydrogen, C_ι-C₆ alkyl , or C₃-C₇ cycloalkyl , Cι-C₆ alkylamino (Ci-Cg) alkyl , or Ci-Cg alkoxy (C**.-

C₆) alkyl ; or

NR³R⁴ examprepresents a 5, 6, or 7-membered heterocyclic ring, such as for example, imidazolyl, pyrrolidinyl , morpholinyl, N- unsubstituted or N- (Ci-Cg) alkyl piperazinyl, or piperidinyl .

Preferred compounds of Formula XXVI containing a G group of Formula XXVI-1 are those where q is 0 or A is methylene or ethylene. Thus, preferred G groups are phenyl, benzyl, and

-33- phenylethyl groups where the phenyl portion of each carries R¹¹, R^11', R¹², R^12', and R¹³.

More preferred groups of Formula XXVI-1 in Formula XXVI are those where R¹¹, R^11' , R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, C**_.- C₆ alkyl, Cχ-Cg alkoxy, or mono- or di (Cι~Cg) alkylamino.

More preferred compounds of Formula XXVI having G groups of Formula XXVI-1 include those where any three of R¹¹, R^11' , R¹², R^12', and R¹³ are hydrogen. Other more preferred groups of Formula XXVI-1 are those where R^11' and R^12' are hydrogen and R¹¹, R¹², and R¹³ independently represent hydrogen, halogen, hydroxy, Ci-Cg alkoxy, or Ci-C alkyl. Still more preferred compounds of Formula XXVI-1 are those where R^11' , R¹², and R^12' are hydrogen and R¹¹ and R¹³ independently represent hydrogen, halogen, hydroxy, or Cι-C₆ alkoxy.

Other preferred compounds of XXVI having G groups of Formula XXVI-1 are those where

R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C_e alkoxy, or mono- or di ( C - Cβ) alkylamino; and

R¹², R^12', and R¹³ are the same or different and represent halogen, C*^*.-C₆ alkyl, R²OY- , where Y is a bond or Ci- C alkylene and R² is as defined above and R², when R² is not hydrogen, is optionally substituted with - NR³R⁴.

^■34* More preferred G groups of Formula XXVI-1 are those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group. Other more preferred groups of Formula XXVI-1 are those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or Ci-Cg alkyl. A particularly preferred set of these more preferred groups of Formula XXVI-1 are those where one of R¹¹ and R^11' is halogen, hydroxy, or C**_.-Cg alkoxy.

Still other preferred compounds of XXVII where G is Formula XXVI-1 are those where

R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Ci-Cg alkyl, Cι-C₆ alkoxy, or mono- or di (Ci- C₆) alkylamino; and

R¹², R^12' , and R¹³ are the same or different and represent hydrogen, halogen, or Cι-C₆ alkyl substituted on its alkyl portion with -NR³R⁴, provided that at least one of R¹², R^12', and R¹³ is substituted Cι-C₆ alkyl. Preferred NR³R⁴ groups substituted on the R¹², R^12' , and R¹³ groups are morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl .

Preferred R³ and R⁴ groups substituted on the R¹², R^12' , and R¹³ groups are hydrogen and Cι-C₆ alkyl groups. More preferably, only one of R³ and R⁴ is an alkyl group.

-35- Other preferred compounds of Formula XXVI include those where R is Cι-C₆ alkyl, mono- or di (Cι-C₆) alkylamino (Ci- C₆) alkyl, Cι-C₆ alkoxy (Ci-Cg) alkoxy, or alkoxy (C_x-C₆) alkyl . Particularly preferred R groups include methyl, ethyl, propyl, butyl, methylaminoethyl , methoxyethoxy, dimethylaminoethyl , butyl, methoxyethyl, dimethylaminopropyl, diethylaminopropyl, ethoxymethoxy, isobutylaminoethyl , and propoxymethyl .

Other preferred G groups in Formula XXVI are encompassed by the Formula XXVI-2:

wherein

A is methylene substituted with R⁵R⁶, where R⁵ and R⁶ independently represent hydrogen or Cι-C₆ alkyl; q is 0 or an integer of from 1-3; R represents

R²OY- where Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or

-36* Ci-Cg alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₃ alkyl, -OR², -

NR³R⁴ ; R¹², R^12' , and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl , -NR³R⁴; R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴;

Ci-C alkoxy or Cι-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or R¹¹ and R¹², or R¹² and R¹³ together with the atoms to which they are attached form an aryl, heteroaryl, or

(hetero) cyclic ring; or Y and R³ or R⁴ together form a 5, 6, or 7-membered heterocyclic ring with one of the alkyl groups of NR³R⁴ ; Y is Ci-Cg alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; and R³ and R⁴ are the same or different and represent hydrogen, Ci-C alkyl, or C₃-C₇ cycloalkyl, Cι-C₆ alkylamino (Ci-Cg) alkyl, or Cι-C₆ alkoxy (C_x- C₆) alkyl; or

•37* NR³R⁴ represents a 5, 6, or 7-membered heterocyclic ring, such as for example, imidazolyl, pyrrolidinyl, morpholinyl, N-unsubstituted or N- (Ci-Cg) alkyl piperazinyl, or piperidinyl.

Preferred groups of Formula XXVI-2 are those where q is 0 or A is methylene or ethylene. Thus, preferred G groups are cyclohexyl and cyclohexylmethyl groups .

More preferred groups of Formula XXXI -2 are those where R¹¹, R^11', R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Cι-C₆) alkylamino.

Other preferred groups of XXXI -2 are those where R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Ci-

C₆) alkylamino; and R¹², R^12', and R¹³ are the same or different and represent halogen, Cι-C₆ alkyl, R²OY- , where Y is a bond or Ci- C₆ alkylene and R² is as defined above and R², when R² is not hydrogen, is optionally substituted with -

NR³R⁴.

More preferred compounds of Formula XXVI having groups of

Formula XXVI-2 are those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where

NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or

-38- O 99/40092

pyrrolidinyl group. Other more preferred compounds of Formula XXXI having a G group of Formula XXVI -2 are those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or Ci-C alkyl. A particularly preferred set of these more preferred compounds of Formula XXVI are those where one of R¹¹ and R^11' is halogen, hydroxy, or Cι-C₃ alkoxy.

Other preferred compounds of Formula XXVI are those of where G represents pyridyl groups of Formula XXVI-3: =E

* •r(A)*,

Ri D

//

-1"1 R12

XXVI-3 wherein

T is nitrogen or CR^11', E is nitrogen or CR^12', and D is nitrogen or CR¹³, provided that no more than one of

T, E and D is nitrogen; A is methylene substituted with R⁵R⁶, where R⁵ and R⁶ independently represent hydrogen or Cι-C₆ alkyl; q is 0 or an integer of from 1-3; R represents

R²OY- where Y is Cι-C₆ alkylene and R² represents hydrogen, C_x-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are

^•39- independently optionally substituted with -NR³R⁴; or C_x-C₆ alkyl, C_x-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group;

R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, C_x-C₆ alkyl, -OR², - NR³R⁴ ; R¹², R^12' , and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl, -NR³R⁴;

R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; C_x-C₆ alkoxy or C_x-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

(hetero) cyclic ring; or

NR³R⁴ ;

Y is Ci-Cg alkylene and R² represents hydrogen, Cι-C₆ alkyl , or C₃-C cycloalkyl ; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl , or C₃-C₇ cycloalkyl , Ci-Cg

-40 - alkylamino (Ci-Cg) alkyl, or C_x-C₆ alkoxy (Ci-

C₆) alkyl; or

NR³R⁴ represents a 5, 6, or 7-membered heterocyclic ring, such as for example, imidazolyl, pyrrolidinyl, morpholinyl, N-unsubstituted or

N- (Ci-Cg) alkyl piperazinyl, or piperidinyl. Preferred groups of Formula XXVI -3 are those where one and only one of T, E, and D is nitrogen.

Preferred compounds containing pyridyl groups of Formula XXVI-3 are those where q is 0 or A is methylene or ethylene.

More preferred compounds having a G group of Formula XXVI-3 are those where R¹¹, R^11' , R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Ci-Cg alkyl, C_x-C₆ alkoxy, or mono- or di (C_x-C₃) alkylamino. More preferred compounds having a G group of Formula XXVI-3 include those where any three of R¹¹, R^11', R¹², R^12', and R¹³ are hydrogen. Other more preferred groups of Formula XXVI- 3 are those where R^11' and R^12' are hydrogen and R¹¹, R¹², and R¹³ independently represent hydrogen, halogen, hydroxy, C_x-C₆ alkoxy, or Cι-C₆ alkyl. Still more preferred groups of Formula XXVI -3 are those where R^11' , R¹², and R^12' are hydrogen and R¹¹ and R¹³ independently represent hydrogen, halogen, hydroxy, or Ci-Cg alkoxy.

Other preferred groups of Formula XXVI -3 are those where

-41- R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Ci- C₆) alkylamino; and

R¹², R^12', and R¹³ are the same or different and represent halogen, Cι-C₆ alkyl, R²OY- , where Y is a bond or Ci-

C₆ alkylene and R² is as defined above and R², when R² is not hydrogen, is optionally substituted with -

NR³R⁴.

More preferred groups of Formula XXVI -3 are those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group. Other more preferred compounds having a group of Formula XXVI-3 are those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or Cι-C₆ alkyl. A particularly preferred set of these more preferred compounds having a group of Formula XXVI-3 are those where one of R¹¹ and R^11' is halogen, hydroxy, or Cι-C₆ alkoxy.

Preferred NR³R⁴ groups substituted on the R¹², R^12' , and R¹³ groups are morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl .

-42*

XXVII where R⁷, R, and G are defined above.

Preferred compounds of Formula XXVII are those of where R represents

R²OY- where Y is C_x-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or

Ci-Cg alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; and G represents a group of Formula XXVII-1:

R¹² _R13

R^{1 1}- A A .

:-(A)_q V

XXVI I - 1 wherein

A is methylene substituted with R⁵R⁶, where R⁵ and R⁶ independently represent hydrogen or Ci-C₆ alkyl; q is 0 or an integer of from 1-3;

-43* R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², - NR³R⁴ ; R¹², R^12' , and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl , -NR³R⁴;

R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-Cg alkoxy or C_x-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

(hetero) cyclic ring; or

NR³R⁴;

Y is Ci-C alkylene and R² represents hydrogen, Cι-C₆ alkyl , or C₃-C₇ cycloalkyl ; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₃ alkyl , or C₃-C₇ cycloalkyl , Cι-C₆ alkylamino (Ci-C ) alkyl , or Cι-C₆ alkoxy (Ci-

Cg) alkyl ; or

N- (Ci-Cg) alkyl piperazinyl, or piperidinyl. -44- Preferred groups of Formula XXVII -1 are those where q is 0 or A is methylene or ethylene. Thus, preferred G groups are phenyl , benzyl , and phenylethyl groups where the phenyl portion of each carries R¹¹, R^11' , R¹², R^12', and R¹³.

More preferred groups of XXVII-1 are those where R¹¹, R^11' , R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, C_ι-C₆ alkoxy, or mono- or di (Cι-C₆) alkylamino. More preferred compounds of Formula XXVII including groups of Formula XXVII -1 include those where any three of R¹¹, R^11', R¹², R^12', and R¹³ are hydrogen. Other more preferred compounds of Formula XXVII are those having G groups of Formula XXVII-1 where R^11' and R^12' are hydrogen and R¹¹, R¹², and R¹³ independently represent hydrogen, halogen, hydroxy, C_ι-C₆ alkoxy, or Cι-C₆ alkyl. Still more preferred groups of Formula XXVII-1 are those where R^11' , R¹², and R^12' are hydrogen and R¹¹ and R¹³ independently represent hydrogen, halogen, hydroxy, or Ci-Cg alkoxy.

Other preferred groups of XXVII -1 are those where

R¹¹ and R¹¹ independently represent hydrogen, halogen, hydroxy, C_x-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Ci-

C₆) alkylamino; and R¹², R^12', and R¹³ are the same or different and represent halogen, Cι-C₆ alkyl, R²0Y- , where Y is a bond or Ci-

-45- C₆ alkylene and R² is as defined above and R², when R² is not hydrogen, is optionally substituted with - NR³R⁴.

More preferred groups of Formula XXVII-1 are those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group. Other more preferred groups of Formula XXVII-1 are those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or Ci-C alkyl. A particularly preferred set of these more preferred groups of Formula XXVII -1 are those where one of R¹¹ and R^11' is halogen, hydroxy, or Ci-Cg alkoxy. Still other preferred compounds of XXVII are those having G groups of Formula XXVII-1 where

R¹¹ and R¹¹ independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Ci- C₆) alkylamino; and R¹², R^12', and R¹³ are the same or different and represent hydrogen, halogen, or C_ι-C₆ alkyl substituted on its alkyl portion with -NR³R⁴, provided that at least one of R¹², R^12', and R¹³ is substituted Ci-Cg alkyl. Preferred NR³R⁴ groups substituted on the R¹², R^12' , and R¹³ groups are morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl .

-46- Preferred R³ and R⁴ groups substituted on the R¹², R^12', and R¹³ groups are hydrogen and C_x-C₆ alkyl groups. More preferably, only one of R³ and R⁴ is an alkyl group.

Other preferred compounds of Formula XXVII include those where R is C_x-C₆ alkyl, mono- or di (Cι-C₆) alkylamino (C_x- C₆) alkyl, Cι-C₆ alkoxy (Cι-C₆) alkoxy, or alkoxy (C_x-C₆) alkyl . Particularly preferred R groups include methyl, ethyl, propyl, butyl, methylaminoethyl , methoxyethoxy, dimethylaminoethyl, butyl, methoxyethyl, dimethylaminopropyl, diethylaminopropyl, ethoxymethoxy, isobutylaminoethyl , and propoxymethyl .

Other preferred G groups in Formula XXVII are encompassed by the formula XXVII-2:

XXVII -2 wherein

R²OY- where Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are

-47- independently optionally substituted with -NR³R⁴; or Ci-Cg alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group;

R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², - NR³R⁴ ; R¹², R^12', and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl, -NR³R⁴;

R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-Cg alkoxy or Cι-C_e alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

R¹¹ and R¹², or R¹² and R¹³ together with the atoms to which they are attached form an aryl , heteroaryl , or

(hetero) cyclic ring; or

NR³R⁴ ;

Y is Ci-Cg alkylene and R² represents hydrogen, Cι-C₃ alkyl , or C₃ -C₇ cycloalkyl ; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl , or C₃-C₇ cycloalkyl , Cι-C₆

-48 * alkylamino (Ci-Cg) alkyl, or Cι-C₆ alkoxy (Ci-

C₆) alkyl; or

N- (C_x-Cg) alkyl piperazinyl, or piperidinyl.

Preferred groups of Formula XXVII -2 are those where q is 0 or A is methylene or ethylene. Thus, preferred G groups are cyclohexyl and cyclohexylmethyl groups.

More preferred groups of XXVII -2 are those where R¹¹, R^11' , R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Cχ-C₆ alkyl, C_x-C₆ alkoxy, or mono- or di (Cι-C₆) alkylamino. Other preferred groups of XXVII -2 are those where

R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, C_x-C₆ alkyl, C_x-C₆ alkoxy, or mono- or di (C_x- C₆) alkylamino; and R¹², R^12', and R¹³ are the same or different and represent halogen, C_x-C₆ alkyl, R²OY- , where Y is a bond or C_x-

C₆ alkylene and R² is as defined above and R², when R² is not hydrogen, is optionally substituted with - NR³R⁴.

More preferred compounds of Formula XXVII having G groups of Formula XXVII -2 are those where Y is a bond, methylene, or

-49- ethylene, R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group. Other more preferred groups of Formula XXVII -2 are those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or C_x-C₆ alkyl. A particularly preferred set of these more preferred groups of Formula XXVII-2 are those where one of R¹¹ and R^11' is halogen, hydroxy, or Cι-C₆ alkoxy.

Other preferred compounds of Formula XXVII are those of where G represents a group of Formula XXVII-3:

wherein

T is nitrogen or CR^11' , E is nitrogen or CR^12', and D is nitrogen or CR¹³, provided that no more than one of T, E and D is nitrogen; A is methylene substituted with R⁵R⁶, where R⁵ and R⁶ independently represent hydrogen or C_x-C₆ alkyl; q is 0 or an integer of from 1-3; R represents

R²OY- where Y is Cι-C₆ alkylene and R² represents hydrogen, C_x-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y

-50- and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or

C_x-Cg alkyl, Ci-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², - NR³R⁴ ; R¹², R^12', and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl , -NR³R⁴; R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-Cg alkoxy or Cι-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or R¹¹ and R¹², or R¹² and R¹³ together with the atoms to which they are attached form an aryl, heteroaryl, or (hetero) cyclic ring; or Y and R³ or R⁴ together form a 5, 6, or 7-membered heterocyclic ring with one of the alkyl groups of NR³R⁴ ;

Y is Ci-Cg alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; and R³ and R⁴ are the same or different and represent hydrogen, Ci-C₆ alkyl, or C₃-C₇ cycloalkyl, C_x-C₆ -51- alkylamino (Ci-Cg) alkyl, or C_x-C₆ alkoxy (Ci-

C₆) alkyl; or

NR³R⁴ represents a 5, 6, or 7-membered heterocyclic ring, such as for example, imidazolyl , pyrrolidinyl, morpholinyl, N-unsubstituted or

N- (Ci-Cg) alkyl piperazinyl, or piperidinyl. Preferred groups of Formula XXVII -3 are those where one and only one of T, E, and D is nitrogen.

Preferred groups containing Formula XXVII -3 are those where q is 0 or A is methylene or ethylene.

More preferred compounds having a G group of Formula XXVII -3 are those where R¹¹, R^11', R¹², R^12' , and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Ci-C alkyl, Cι-C₆ alkoxy, or mono- or di (Ci-Cg) alkylamino .

More preferred compounds having a G group of Formula XXVII-3 include those where any three of R¹¹, R^11' , R¹², R^12' , and R¹³ are hydrogen. Other more preferred groups of Formula XXVII -3 are those where R^11' and R^12' are hydrogen and R¹¹, R¹², and R¹³ independently represent hydrogen, halogen, hydroxy, C_x- C₆ alkoxy, or Cι-C₆ alkyl. Still more preferred groups of Formula XXVII -3 are those where R^11' , R¹², and R^12' are hydrogen and R¹¹ and R¹³ independently represent hydrogen, halogen, hydroxy, or C_x-C₆ alkoxy.

Other preferred groups of Formula XXVII -3 are those where

-52- R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, C_x-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (C**_.- C₆) alkylamino; and R¹², R^12', and R¹³ are the same or different and represent halogen, C_x-C₆ alkyl, R²OY-, where Y is a bond or C_x-

Other moe preferred groups of Formula XXVII -3 include those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group. Other more preferred compounds having a group of Formula XXVII -3 are those where Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or C_x-C₆ alkyl. A particularly preferred set of these more preferred groups of Formula XXVII are those carrying a group of Formula XXVII -3 where one of R¹¹ and R^11' is halogen, hydroxy, or C_x-C₆ alkoxy.

^•53*

XXVIII where R⁷, R, and G are defined above.

R 7_

XXIX where R⁷, R, and G are defined above.

Preferred compounds of Formula XXIX are those of where G represents Formula XXIX- 1:

^Ry /^Rl3

"ⁱ -l _R11

XXI^tX- 1:" where R¹¹, R^11' , R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (d-Cg) alkylamino.

More preferred compounds containing Formula XXIX-1 include those where any three of R¹¹, R^11' , R¹², R^12', and R¹³ are hydrogen. Other more preferred containing Formula XXIX- 1 are those where R^11' and R^12' are hydrogen and R¹¹, R¹², and R¹³

^■54* independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkoxy, or Ci-C₆ alkyl.

-

R 7_

XXX where R⁷, R, R¹⁸, and G are defined above.

Preferred compounds of Formula XXX are those containing a G group of the Formula XXX- 1

XXX-1 wherein

A is methylene substituted with R⁵R⁶, where R⁵ and R⁶ independently represent hydrogen or C_x-C₆ alkyl; q is 0 or an integer of from 1-3; R represents

ROY- where Y is Cι-C₆ alkylene and R² represents hydrogen, C_x-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R , when R² is not hydrogen, are

^•55- independently optionally substituted with -NR³R⁴; or Ci-C alkyl, C_x-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group;

R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², - NR³R⁴ ; R¹², R^12', and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl , -NR³R⁴;

R¹² and R¹³ together with the atoms to which they are attached form a (hetero) cyclic ring; or Y and R³ or R⁴ together form a 5, 6, or 7-membered heterocyclic ring with one of the alkyl groups of NR³R⁴;

Y is Ci-C alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; and R³ and R⁴ are the same or different and represent hydrogen, C_x-C₆ alkyl, or C₃-C₇ cycloalkyl, C_x-Cg alkylamino (Ci-Cg) alkylene, or C_x-C₆ alkoxy (Ci-

Cg) alkyl; or

-56- NR .3τR-,4 represents a 5, 6, or 7-membered heterocyclic ring, such as for example, imidazolyl, pyrrolidinyl, morpholinyl, N-unsubstituted or N- (Ci-Cg) alkyl piperazinyl, or piperidinyl.

Preferred groups of Formula XXX- 1 are those where q is 0 or A is methylene or ethylene. Thus, preferred G groups are phenyl and benzyl groups carrying R¹¹, R^11' , R¹², R^12', and R¹³ .

More preferred groups of XXX-1 are those where R¹¹, R^11' , R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Cι-C₆) alkylamino.

Other more preferred groups of Formula XXX-1 are those where R¹⁸ is Cι-C₆ alkyl; and R¹¹, R^11' , R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, C_x-C₆ alkyl, Ci-C₆ alkoxy, or mono- or di (Ci- C₆) alkylamino. Particularly preferred groups of Formula XXX-1 are those where R¹⁸ is Cι-C₆ alkyl; and one or two of R¹¹, R¹³, and R¹² is halogen, preferably fluoro, and R^12', and R^11' are hydrogen .

-57-

XXXI

where R⁷, R, R¹⁸, and G are defined above.

f \— N β

R W

XXXII where R⁷, R, R¹⁸, and G are defined above,

^>

R⁷-

Υ R¹⁸

XXXIII where R , R, R , and G are defined above

Intermediates useful in making compounds of the invention include compounds of: Formula A-l :

ZI^RN

^^CO₂R_e

A-l -58- where Z_x, Z₂, Z₃, and Z₄ are as defined above for Formula I; R_N is nitro or mono- or di (C_x-C₆) alkylamino; R_p is hydrogen or Ci-Cg alkyl; and R_e is hydrogen or Cι-C₆ alkyl.

Preferred compounds of Formula A-l are those of Formulae A-2, A-3 and A-4 :

N

^ ^.CO₂R_e CO₂R_e

N

R' Rn R' R,

A-2 A-3

ι - .-^^CO₂R_e

R" N N

I

R

A-4 where R_N is nitro or mono- or di (C_x-C₆) alkylamino; R_p is hydrogen or Cι-C₆ alkyl; R_e is hydrogen or Cι-C₆ alkyl; and each R⁷ independently carries the definition given above in Formula I.

Formula B-l:

^Z1-^N CO₂R

I ^

^•N

CO₂R_e

B-l

^•59- where Z_1# Z₂, Z₃, and Z₄ are as defined above for Formula I; and each R_e is independently hydrogen or Cι-C₆ alkyl.

Preferred compounds of Formula B-l are those of Formulae B-2, B-3, and B- :

R'

N ■ N C0₂R_e CO₂R_e

N

CO Rp

R⁷

B-2 B-3

R⁷

• N CO₂R_e

^ /

^•N^{' •} ^•NNl

CO₂R_e

B-4 where each R_e is hydrogen or C_x-C₆ alkyl; and each R⁷ independently carries the definition given above in Formula I.

Formula C-l

H O R_c z - ^N -O

-3"? N ^:O

c-i where Z_x, Z₂, Z₃, and Z₄ are as defined above for Formula I; and R_e is hydrogen or Ci-C₆ alkyl.

-60- Preferred compounds of Formula C-l are those of Formulae C-2, C-3, and C-4 :

I /i' o^υ I i o

.Re

I T

C-2 ^W C-3

C-4 where R_e is hydrogen or C*_L-C₆ alkyl; each R⁷ independently carries the definition given above in Formula I; and Ri carries the definition set forth above for R in Formula I.

Preferably, in each of C-2, C-3, and C-4, Ri is hydrogen, or more preferably, Ci-C alkyl, mono- or di- (Ci- Cg) alkylamino (Cι-C₃) alkyl, or Ci-Cg alkoxy (Ci-Cg) alkyl; R_e is hydrogen or C**.-C₆ alkyl; and each R⁷ independently carries the definition given above in Formula I.

In certain situations, compounds of Formula I may contain one or more asymmetric carbon atoms, so that the compounds can exist in different stereoisomeric forms. These compounds can be, for example, racemates or optically active forms. In these situations, the single enantiomers, i. e., optically active

-61- forms, can be obtained by asymmetric synthesis or by resolution of the racemates. Resolution of the racemates can be accomplished, for example, by conventional methods such as crystallization in the presence of a resolving agent, or chromatography, using, for example a chiral HPLC column.

Representative compounds of the present invention, which are encompassed by Formula I, include, but are not limited to the compounds in Table I and their pharmaceutically acceptable acid and base addition salts. In addition, if the compound of the invention is obtained as an acid addition salt, the free base can be obtained by basifying a solution of the acid salt. Conversely, if the product is a free base, an addition salt, particularly a pharmaceutically acceptable addition salt, may be produced by dissolving the free base in a suitable organic solvent and treating the solution with an acid, in accordance with conventional procedures for preparing acid addition salts from base compounds .

Non-toxic pharmaceutical salts include salts of acids such as hydrochloric, phosphoric, hydrobromic, sulfuric, sulfinic, formic, toluenesulfonic, methanesulfonic, nitic, bencoic, citric, tartaric, maleic, hydroiodic, alkanoic such as acetic, HOOC- (CH₂) _n-A_cOOH where n is 0-4, and the like. Non- toxic pharmaceutical base addition salts include salts of bases such as sodium, potassium, calcium, ammonium, and the like. Those skilled in the art will recognize a wide variety of non-toxic pharmaceutically acceptable addition salts.

-62- The present invention also encompasses the acylated prodrugs of the compounds of Formula I . Those skilled in the are will recognize various synthetic methodologies which may be employed to prepare non-toxic pharmaceutically acceptable addition salts and acylated prodrugs of the compounds encompassed by Formula I .

By lower alkyl or C_x-C₆ alkyl in the present invention is meant straight or branched chain alkyl groups having 1-6 carbon atoms, such as, for example, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl , 2-pentyl, isopentyl, neopentyl, hexyl , 2-hexyl, 3-hexyl, and 3- methylpentyl .

By cycloalkyl, e.g., C₃-C₇ cycloaklyl, in the present invention is meant cycloalkyl groups having 3-7 atoms such as, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl .

By aryl is meant an aromatic carbocyclic group having a single ring (e. g., phenyl), multiple rings (e. g. , biphenyl) , or multiple condensed rings in which at least one is aromatic, (e. g., 1,2 , 3 , 4-tetrahydronaphthyl, naphthyl, anthryl , or phenanthryl) , which is optionally mono-, di-, or trisubstituted with, e. g. , halogen, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy, mono- or di-alkylamino.

By lower alkoxy or Cι-C₆ alkoxy in the present invention is meant straight or branched chain alkoxy groups having 1-6 carbon atoms, such as, for example, methoxy, ethoxy, propoxy,

-63- isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentoxy, 2- pentyl, isopentoxy, neopentoxy, hexoxy, 2-hexoxy, and 3- methylpentoxy.

By halogen in the present invention is meant fluorine, bromine, chlorine, and iodine.

By "R³ and R⁴ may be taken together to form a ring" is meant that R³ and R⁴ together with the nitrogen to which they are attached form a 3-7 membered ring. Such 3-7 membered ring may optionally contain an additional hetero atom, e.g., oxygen, nitrogen, or sulfur. Such ring may also be optionally substituted with halogen, lower alkyl, or lower alkoxy.

Where R⁹ and R¹⁰ together with the nitrogen atom to which they are attached form a 5- or 6-membered ring containing at least one nitrogen hetero atom, those groups are heterocyclic moieties. Examples include imidazolyl, pyrrolidinyl, morpholinyl, piperazinyl, and piperidinyl. Groups such as piperazinyl may be substituted on nitrogen to form an 4-N- (C_x- C₆) alkylpiperazin-1-yl group.

Where a substituent is a di (C_ι-C₆) alkylamino group, the two alkyl groups are the same or different. Representative di (Cι-C₆) alkylamino groups include dimethylamino, methylpropylamino, diisopropylamino, and ethylpentylamino .

By (hetero) cyclic ring is meant a ring that is either aliphatic or aromatic and optionally contains at least one hetero atom. Hetero atoms include nitrogen, sulfur, and oxygen. Examples of such (hetero) cyclic rings are

-64- cyclohexyl, cyclopenyl, cyclohexyl, piperidinyl, piperazinyl, pyrrolyl, morpholinyl, pyrimidinyl, imidazolyl, etc.

By hetroaryl (aromatic heterocycle) in the present invention is meant one or more aromatic ring systems of 5-, 6- , or 7-membered rings containing at least one and up to four hetero atoms selected from nitrogen, oxygen, or sulfur. Such heteroaryl groups include, for example, thienyl, furanyl, thiazolyl, imidazolyl, (is) oxazolyl , pyridyl, pyrimidinyl,

(iso) quinolinyl, naphthyridinyl , benzimidazolyl , and benzoxazolyl .

Specific examples of heteroaryl groups are the following:

_R12 _R11

// \\

-_R13 _R13

Rir

RT 3 R¹²

wherein

L is nitrogen or -CR .11;

T is -NR¹⁹, oxygen, or sulfur;

R¹⁹, R¹¹, R¹², R¹³, R^11', and R^12' are as defined above; and

R¹⁹ is hydrogen, lower alkyl having 1-6 carbon atoms.

^■65- The structure of Formula I as shown in the specification and as used in the claims includes all possible tautomers and rotamers . Formulae lie and lid below are illustrative.

Thus, when R = H in Formula I:

O

^■N H

O

lie lid

The following numbering systems are used to identify positions on the dipyridoimidazole ring systems of the compounds of the invention:

The numbering convention used to identify the positions of a pyridine ring substituted with various groups the position at which the pyridine ring is attached to another group is as follows: the pyridine ring nitrogen is assigned position 1.

^■66- Representative compounds of the invention are shown below ble 1.

Table 1

compound 4 compound 12

Ci O

compound 23 compound 43

OMe

compound 45 compound 67

^■67- H

N c

compound 46 compound 68

compound 64 compound 2

compound 82 compound 93

-68*

compound 151 compound 141

compound 143 compound 206

compound 172

The dipyridoimidazole-oxo-carboxamides of Formula I and their salts are suitable for the diagnosis and treatment of

-69- anxiety, Down Syndrome, depression, sleep, cognitive and seizure disorders, and overdose with benzodiazepine drugs and for enhancement of alertness, both in human and non-human animals and domestic pets, especially dogs and cats and farm animals such as sheep, swine and cattle.

The compounds of general Formula I may be administered orally, topically, parenterally, by inhalation or spray or rectally in dosage unit formulations containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants and vehicles. The term parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrasternal injection or infusion techniques. In addition, there is provided a pharmaceutical formulation comprising a compound of general Formula I and a pharmaceutically acceptable carrier. One or more compounds of general Formula I may be present in association with one or more non-toxic pharmaceutically acceptable carriers and/or diluents and/or adjuvants and if desired other active ingredients. The pharmaceutical compositions containing compounds of general Formula I may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsion, hard or soft capsules, or syrups or elixirs.

Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions may

-70- contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preserving agents in order to provide pharmaceutically elegant and palatable preparations. Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets. These excipients may be for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed.

Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin or olive oil. Aqueous suspensions contain the active materials in admixture with excipients suitable for the manufacture of

-71- aqueous suspensions. Such excipients are suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydropropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents may be a naturally-occurring phosphatide, for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol , or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions may also contain one or more preservatives, for example ethyl, or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose or saccharin. Oily suspensions may be formulated by suspending the active ingredients in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. The oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents such as those set forth above, and flavoring agents may be added to provide palatable oral

-72- preparations. These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid.

Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above. Additional excipients, for example sweetening, flavoring and coloring agents, may also be present.

Pharmaceutical compositions of the invention may also be in the form of oil-in-water emulsions. The oily phase may be a vegetable oil, for example olive oil or arachis oil, or a mineral oil, for example liquid paraffin or mixtures of these. Suitable emulsifying agents may be naturally-occurring gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol, anhydrides, for example sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening and flavoring agents.

Syrups and elixirs may be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative and flavoring and coloring agents. The

-73- pharmaceutical compositions may be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents which have been mentioned above. The sterile injectable preparation may also be sterile injectable solution or suspension in a non-toxic parentally acceptable diluent or solvent, for example as a solution in 1, 3-butanediol . Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or diglycerides . In addition, fatty acids such as oleic acid find use in the preparation of injectables.

The compounds of general Formula I may also be administered in the form of suppositories for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Such materials are cocoa butter and polyethylene glycols.

Compounds of general Formula I may be administered parenterally in a sterile medium. The drug, depending on the vehicle and concentration used, can either be suspended or

-74- dissolved in the vehicle. Advantageously, adjuvants such as local anesthetics, preservatives and buffering agents can be dissolved in the vehicle.

Dosage levels of the order of from about 0.1 mg to about 140 mg per kilogram of body weight per day are useful in the treatment of the above- indicated conditions (about 0.5 mg to about 7 g per patient per day) . The amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. Dosage unit forms will generally contain between from about 1 mg to about 500 mg of an active ingredient.

It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, route of administration, and rate of excretion, drug combination and the severity of the particular disease undergoing therapy. For administration to non-human animals, the composition may also be added to the animal feed or drinking water. It will be convenient to formulate these animal feed and drinking water compositions with a mullet -dose of the drug so that the animal takes in an appropriate quantity of the composition along with its diet. It will also be convenient to present the

^■75* composition as a premix for addition to the feed or drinking water.

An illustration of the preparation of compounds of the present invention is given in Scheme 1.

Scheme 1

.COOEt

^^Zi -NO₂ H₂N

HCl

XI K₂CO₃

H

B

HCl Pd/C, H₂ HN ^' COOEt EtOH

^{z Z}'V\ COOEt j -

MeO Z^^Z^^{N H}2 > ^•N -COOEt

COOEt EtOH "A

D c

NaOEt / EtOH

H O H °_\

1^ -N ^■OEt H₂NG »>

^*N Xylenes

O *-• F^£

RI / KOH DMF / H₂O

R o R O NHG _(j^RlS, ^^ ^^N\ _.^NHG

"H =Q (ϋ) NaBH₄ H

In Scheme 1, the substituents R, R⁷, R¹⁸, and G carry the definitions set forth above for Formula I; Z_i# Z₂, Z₃, and Z₄

-76- independently represent N or CR⁷ in Formulas A, B, C, D, E, F, and G; and Zi, Z₂, Z₃, and Z₄ independently represent NR¹⁸ or CR⁷ in Compound H.

Those having skill in the art will recognize that the starting materials may be varied and additional steps employed to produce compounds encompassed by the present inventions, as demonstrated by the following examples. In some cases, protection of certain reactive functionalities may be necessary to achieve some of the above transformations. In general, the need for such protecting groups will be apparent to those skilled in the art of organic synthesis as well as the conditions necessary to attach and remove such groups.

The disclosures in this application of all articles and references, including patents, are incorporated herein by reference.

The invention is illustrated further by the following examples which are not to be construed as limiting the invention in scope or spirit to the specific procedures described in them.

EXAMPLE 1 Preparation of starting materials and intermediates

The starting materials and various intermediates may be obtained from commercial sources, prepared from commercially available organic compounds, or prepared using well know synthetic methods.

-77- Representative examples of methods for preparing intermediates of the invention are set forth below.

,N NOU,,

NT

1* II COOEt N H

To a mixture of 4-chloro-3-nitropyridine (6 g, 37.8 mmol) and potassium carbonate (15.7 g, 113.4 mmol) in N,N- dimethylformamide (45 mL) was added dropwise a solution of alanine ethyl ester hydrochloride (5.8 g, 37.8 mmol) in N,N- dimethylformamide (45 mL) at room temperature. The mixture was then stirred at rt for 22 h. Ethyl acetate (200 mL) and brine (150 mL) were added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL) . The combined organic layer was washed with water (100 x 6) and dried (Na₂S0₄) . Evaporation of the solvent gave 8.2 g of 3- nitro-4- [2- (ethoxycarbonyl) ethylamino] pyridine as a yellowish solid.

-NH,

N N^'' ^r

.COOEt

A mixture of 3-nitro-4- [2- (ethoxycarbonyl) ethylamino] - pyridine (8.2 g) and 10% Pd/C (410 mg) in ethanol (180 mL) was placed in a Paar bottle and shaken under hydrogen (50 PSI) for

4 h. The mixture was filtered through Celite and concentrated

-78- in vacuo to afford 7.7 g of 3 -amino-4- [2- (ethoxycarbonyl) ethylamino] pyridine as a dark solid.

^N Λ /^CO0Et COOEt

A mixture of of 3 -amino-4- [2- (ethoxycarbonyl) ethylamino] - pyridine (7.7 g, 36.8 mmol) and ethyl 3-amino-3-ethoxy- acrylate hydrochloride (7.2 g, 36.8 mmol) in ethanol (100 mL) was refluxed under N₂ for 20 h. Another portion of ethyl 3- amino-3-ethoxy-acrylate hydrochloride (7.2 g, 36.8 mmol) was added. The mixture was refluxed for an additional 3 h. The solvent was removed in vacuo. Ethyl acetate (150 mL) and aqueous potassium carbonate (100 mL) were added to the residue. The organic layer was separated and washed with K₂C0₃ (aq.) and then water. After drying (Na₂S0₄) , the solvent was removed to afford 10.7 g of 1- [2- (ethoxycarbonyl) ethyl] -2 -

[ (ethoxycarbonyl) methyl] -lH-imidazo [4, 5-c] pyridine as a dark oil.

To ethanol (80 'mL) ^cwas added^£sodiuτm metal (807 mg, 35.1 mmol) under N₂. After the sodium disappeared, a solution of of

-79- 1- [2- (ethoxycarbonyl) ethyl] -2- [ (ethoxycarbonyl) methyl] -1H- imidazo [4, 5-c] pyridine (10.7 g, 35.1 mmol) in ethanol (50 mL) was added dropwise. The mixture was then stirred at room temperature overnight. The solvent was removed at 40°C in vacuo till dryness . Water (20 mL) was added to the residue. Sodium phosphate monobasic was added slowly till pH - 7. The solid was filtered, rinsed with water, and dried to give 6.5 g of 8-oxo-9-ethoxycarbonyl-6, 7, 8 , 10-tetrahydro-dipyrido [1,2- a:3 ' , 4 ' -d] imidazole as a colorless solid.

EXAMPLE 2

H Q

N

U

N -O

A mixture of 8-oxo-9-ethoxycarbonyl-6 , 7 , 8 , 10-tetrahydro- dipyrido[l,2-a:3' ,4' -d] imidazole (100 mg, 0.386 mmol) and 2- fluorobenzylamine (194 mg, 1.54 mmol) in xylenes (70 mL) was refluxed for 16 h. The solvent was removed in vacuo till dryness. The solid residue was washed with diethyl ether. Filtration afforded 114 mg of N- (2-fluorobenzyl) -8-oxo- 6,7,8, 10-tetrahydro-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide as a colorless solid; m. p. 218-220°C (Compound 1) .

^■80- 2.

To a solution of N- (2-fluorobenzyl) -8 -oxo-6, 7, 8 , 10- tetrahydro-dipyrido [l,2-a:3 ' ,4'-d] imidazole-9-carboxamide (300 mg, 0.888 mmol) in N,N-dimethylformamide (12 mL) was added a solution of potassium hydroxide (300 mg) in 4 drops of water. After 5 min, methyl iodide (189 mg, 1.33 mmol) was added. The mixture was stirred at room temperature overnight . Chloroform (30 mL) and water (30 mL) were added. The organic layer was separated and washed with sodium hydroxide aqueous solution (1 N) 4 times. After drying, the solvent was removed in vacuo. The residue was subjected to preparative TLC twice to afford 10 mg of N- (2-fluorobenzyl) -8-oxo-10-methyl-6, 7, 8, 10- tetrahydro-dipyrido [l,2-a:3' ,4' -d] imidazole- 9-carboxamide as a colorless solid; m. p. 247-249°C (Compound 2) .

Mβ_\

A mixture of N- (2-fluorobenzyl) -8-oxo-6, 7, 8 , 10- tetrahydro-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide (125 mg, 0.370 mmol) and methyl iodide (4 mL) was refluxed for 2 days. Removal of the excess amount of methyl iodide afforded

-81- 140 mg of N- (2-fluorobenzyl) -2-methyl-8-oxo-6, 7 , 8 , 10- tetrahydro-dipyrido [1, 2-a:3 ' ,4' -d] imidazole- 9 -carboxamide iodide as a colorless solid.

To the suspension of N- (2-fluorobenzyl) -2-methyl-8-oxo- 6,7,8, 10-tetrahydro-dipyrido [l,2-a:3',4'-d] imidazole- 9- carboxamide iodide (140 mg, 0.293 mmol) in ethanol (15 mL) was added sodium borohydride (100 mg) potionwise at -10°C under N₂. The mixture was stirred at this temperature for an additional 3 h, then 3 drops of acetic acid was added. After 5 min., the solvent was removed in vacuo. The residue was treated with methylene chloride (30 mL) and water (30 mL) . The organic layer was separated and the aqueous layer extracted with methylene chloride (2 X 15 mL) . The combined organic layer was dried (Na₂S0₄) and the solvent evaporated. The residue was subjected to preparative TLC to give 18 mg of N- (2 -fluorobenzyl) -2-methyl-8-oxo-l , 2 , 3 , 4 , 6,7,8, 10-8H- dipyrido [1 , 2-a : 3 ' , 4 ' -d] imidazole-9-carboxamide as a colorless solid; m. p. 113-115°C (Compound 3) .

EXAMPLE 3

The following compounds were prepared essentially according to the procedures described in Examples 1-2:

(a) N-Phenyl-7-oxo-5,7,8,9-4H-dipyrido[l,2-a:3' ,2' - d] imidazole- 6 -carboxamide; m.p. 148-150°C (Compound 4) .

^■82* (b) N- (2 -Fluorophenyl) -7-oxo-5,7, 8, 9-4H-dipyrido [1, 2- a:3 ' , 2' -d] imidazole-6 -carboxamide; m.p. 262-264°C (Compound 5).

(c) N- (2 -Fluorophenyl) -8-oxo-6, 7,8, 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 253-256°C (d) (Compound

6) .

(d) N-Phenyl-8-oxo-6,7,8, 10-4H-dipyrido [1, 2 -a: 3 ' ,4' - d] imidazole- 9-carboxamide; m.p. 225-230°C (Compound 7).

(e) N- (3- ethoxyphenyl) -8-oxo-6, 7, 8 , 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 286-290°C (Compound 8),

(f) N- (4-Ethoxyphenyl) -8-oxo-6, 7,8, 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole- 9 -carboxamide; m.p. 252-255°C (Compound 9)

(g) N- (4 -Fluorophenyl) -8-oxo-6, 7,8, 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole-9-carboxamide; m.p. 300-301°C (Compound

10) .

(h) N- (2 -Chlorophenyl) -8-oxo-6, 7, 8 , 10-4H-dipyrido [1,2- a:3 ' , 4' -d] imidazole-9 -carboxamide; m.p. 268-271°C (Compound

11) •

(i) N-Benzyl-8-oxo-6,7, 8, 10-4H-dipyrido [1 , 2-a: 3 ' ,4' - d] imidazole- 9-carboxamide; m.p. 220-221°C (Compound 12) .

-83- (j) N-Cyclohexyl-8-oxo-6,7,8, 10-4H-dipyrido [1, 2 -a: 3 ' ,4' d] imidazole-9-carboxamide; m.p. 170-171°C (Compound 13).

(k) N- (4-Fluorobenzyl) -8-oxo-6,7,8, 10-4H-dipyrido [1,2- a:3 ' , 4 ' -d] imidazole-9-carboxamide; m.p. 220-224°C (Compound

14) .

(1) N- (2-Fluorobenzyl) -8-oxo-6, 7, 8 , 10-4H-dipyrido [1, 2- a:3 ' , 4' -d] imidazole-9-carboxamide; m.p. 218-220°C (Compound

15) .

(m) N- (3-Fluorobenzyl) -8-oxo-6,7, 8, 10-4H-dipyrido [1, 2- a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 212-213°C (Compound 16) .

(n) N- (4-Methoxyphenyl) -8-oxo-6, 7,8, 10-4H-dipyrido [1,2- a: 3 ' , 4' -d] imidazole-9-carboxamide; m.p. 250-251°C (Compound 17) .

(o) N- (2-Ethoxybenzyl) -8-oxo-6, 7,8, 10-4H-dipyrido [1,2* a: 3 ' , 4 ' -d] imidazole- 9-carboxamide; m.p. 195-196°C (Compound 18) .

-84- (p) N- (2-Chlorobenzyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1, 2- a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 201-202°C (Compound

19) .

(q) N- (3-Chlorobenzyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1, 2- a:3' ,4' -d] imidazole- 9 -carboxamide; m.p. 221-223°C (d) (Compound

20) .

(r) N- (2,4-Difluorophenyl) -8-0x0-6, 7, 8 , 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 292-295°C (Compound 21) .

(s) N- (2-Fluoro-4-methoxyphenyl) -8-0x0-6, 7,8, 10-4H- dipyrido [1, 2-a:3 ' , 4' -d] imidazole-9-carboxamide; m.p. 256-257°C (Compound 22) .

(t) N- (Cyclohexylmethyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a:3 ' , 4' -d] imidazole-9-carboxamide; m.p. 170-171°C (Compound 23) .

(u) N- (4-Pyridylmethyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a:3 ' , 4' -d] imidazole-9-carboxamide; m.p.255-256°C (Compound 24)

(v) N- (4-Ethoxybenzyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1,2- a:3 ' ,4' -d] imidazole- 9-carboxamide; m.p. 308-310°C (Compound 25) .

-85- (w) N- (3-Pyridylmethyl) -8-0x0-6 , 7, 8 , 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 236-237°C (Compound

26) .

(x) N- (2-Pyridylmethyl) - 8 -oxo- 6, 7, 8 , 10-4H-dipyrido [1, 2- a:3' , 4' -d] imidazole- 9-carboxamide; m.p. 197-198°C (Compound

27) .

(y) N- (2-Methoxyphenyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1 , 2- a: 3 ' , 4 ' -d] imidazole-9-carboxamide; m.p. 257-258°C (Compound

28) .

(z) N- (4-Methoxybenzyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a:3 ', 4' -d] imidazole- 9 -carboxamide; m.p. 190-191°C (Compound

29) .

(aa) N- (2-Methoxybenzyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a:3 ', 4' -d] imidazole- 9-carboxamide; m.p. 216-217°C (Compound 30) .

(bb) N- [2- (4-Methoxyphenyl) ethyl] -8-0x0-6, 7 , 8 , 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide; m.p. 200-201°C (Compound 31) .

^■86* (cc) N- (4-Methylbenzyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 261-262°C (Compound 32) .

(dd) N- (2, 4 -Difluorobenzyl) -8-0x0-6, 7,8, 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 247-248°C (Compound 33) .

(ee) N- (2, 5 -Difluorobenzyl) -8-0x0-6, 7, 8 , 10-4H- dipyrido [1,2 -a:3' , 4' -d] imidazole-9 -carboxamide; m.p. 188-189°C (Compound 34) .

(ff) N- (3-Ethoxypropyl) -8-0x0-6, 7, 8 , 10-4H-dipyrido [1,2- a:3 ', 4' -d] imidazole- 9 -carboxamide; m.p. 186-187°C (Compound 35) .

(gg) N- [3- (Trifluoromethyl) benzyl] -8-0x0-6, 7,8, 10-4H- dipyrido [l,2-a:3 ' ,4' -d] imidazole- 9 -carboxamide; m.p. 260-261°C (Compound 36) .

(hh) N- (2, 5-Difluorophenyl) -8-0x0-6, 7 , 8 , 10-4H- dipyrido [1, 2-a:3' , 4' -d] imidazole-9-carboxamide; m.p. 293-294°C (Compound 37) .

^•87* (ii) N- (2, 6 -Difluorobenzyl) -8-oxo-6, 7, 8 , 10-4H- dipyrido[l,2-a:3' ,4' -d] imidazole- 9 -carboxamide; m.p. 242-243°C (Compound 38) .

(jj) N- (2-Fluoro-4-methylphenyl) -8-oxo-6 , 7, 8 , 10-4H- dipyrido [l,2-a:3^# ,4' -d] imidazole- 9-carboxamide; m.p. 284-285°C (Compound 39) .

(kk) N- (3 -Fluorophenyl) -8-oxo-6, 7, 8 , 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole-9-carboxamide; m.p. 279-281°C (Compound 40) .

(11) N- (2-Fluoro-5-methylphenyl) -8-oxo-6, 7, 8 , 10-4H- dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide; m.p.270-272°C (d) (Compound 41) .

(mm) N- [2-Fluoro-5- (trifluoromethyl) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3' ,4'-d] imidazole-9 -carboxamide ; m.p. 275-277°C (Compound 42) .

(nn) N- [3,4- (Methylenedioxy) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido[l,2-a:3' ,4' -d] imidazole- 9 -carboxamide; m.p .285-286°C (Compound 43) .

^■88* (oo) N- [2- (2 -Fluorophenyl) ethyl] -8-oxo-6 , 7, 8, 10-4H- dipyrido[l,2-a:3' ,4' -d] imidazole- 9 -carboxamide; m.p.198-199°C (Compound 44) .

(pp) N- [1- (4 -Fluorophenyl) ethyl] -8-oxo-6,7, 8, 10-4H- dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide; m.p.176-177°C (Compound 45) .

(qq) N- [4- (1-Imidazolylmethyl) benzyl] -8-oxo-6, 7,8, 10-4H- dipyrido [1,2 -a: 3' ,4' -d] imidazole- 9-carboxamide; m.p.254-255°C (Compound 46) .

(rr) N- (2-Fluoro-4-bromophenyl) -8-oxo-6, 7,8, 10-4H- dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 285-286°C (Compound 47) .

(ss) N- [1- (4-Bromophenyl) ethyl] -8-oxo-6, 7 , 8 , 10-4H- dipyrido [1,2 -a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 131-132°C (Compound 48) .

(tt) N- (2 -Fluoro-4 -chlorophenyl) -8-oxo-6, 7 , 8 , 10-4H- dipyrido [1, 2 -a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 299°C (d) (Compound 49) .

^■89- (uu) N- (1-Indanyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1, 2- a:3' ,4' -d] imidazole-9-carboxamide; m.p. 223-224°C (Compound 50) .

(w) N- (2,3-Difluorophenyl) -8-0x0-6, 7, 8,10-4H- dipyrido [1,2 -a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 281-282°C (Compound 51) .

(ww) N- [1- (Phenyl) ethyl] -8-0x0-6, 7, 8 , 10-4H-dipyrido [1 , 2- a:3 ', 4' -d] imidazole- 9-carboxamide; m.p. 170-174°C (Compound 52) .

(xx) (R) - (+) -N- [1- (Phenyl) ethyl] -8-0x0-6, 7, 8 , 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole- 9-carboxamide; m.p. 172-174°C (Compound 53) .

(yy) (S) - (-) -N- [1- (4-Bromophenyl) ethyl] -8-0x0-6, 7, 8 , 10- 4H-dipyrido [1, 2-a:3 ' , 4' -d] imidazole- 9-carboxamide; m.p. ISO- IS1°C (Compound 54) .

(zz) (S) - (-) -N- [1- (Phenyl) ethyl] -8-0x0-6, 7 , 8 , 10-4H- dipyrido [1, 2-a:3' ,4' -d] imidazole- 9 -carboxamide; m.p. 169-171°C (Compound 55) .

^■90* (aaa) N- [1, 2 , 3 , 4-Tetrahydro-l-naphthyl] -8-oxo- 6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 231-235°C (Compound 56) .

(bbb) N- (2-Fluoro-5-methoxyphenyl) -8-oxo-6, 7, 8 , 10-4H- dipyrido [1,2 -a:3' ,4' -d] imidazole- 9-carboxamide; m.p. 267-268°C (Compound 57) .

(ccc) N- [1-Naphthylmethyl] -8-oxo-6, 7, 8 , 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide; m.p. 235-238°C (Compound 58) .

(ddd) N- (2-Fluoro-4-ethoxyphenyl) -8-oxo-6 , 7, 8 , 10-4H- dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide; m.p. 249-250°C (Compound 59) .

(eee) (S) -N- [1- (1-Naphthyl) ethyl] -8-oxo-6, 7, 8 , 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide; m.p. 136-140°C (Compound 60) .

(fff) N- [(1-Methyl-l -Phenyl) ethyl] -8-oxo-6, 7 , 8 , 10-4H- dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide; m.p. 110°C (d) (Compound 61) .

^•91* (ggg) N- [1- (Phenyl ) propyl] -8-0x0-6 , 7 , 8 , 10-4H- dipyrido [l,2-a:3' , 4' -d] imidazole-9-carboxamide; m.p. 136-139°C (Compound 62) .

(hhh) (R) -N- [1- (1-Naphthyl) ethyl] -8-0x0-6, 7,8, 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide; m.p. 134- 137°C (Compound 63) .

(iii) N- (2 -Fluorophenyl) -2-methyl-8-oxo- 1,2,3,4,6,7, 8,10-8H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide; m.p. 225-227°C (Compound 64).

(j j j ) N- (2-Fluorobenzyl) -2-methyl-8-oxo- 1,2,3,4,6,7,8, 10-8H-dipyrido [1 , 2 -a : 3 ' , 4 ' -d] imidazole-9- carboxamide; m.p. 113-115°C (Compound 65).

(kkk) N- (2-Fluorobenzyl) -8-oxo-10-methyl-6 , 7, 8 , 10-4H- dipyrido [l,2-a:3' , 4' -d] imidazole- 9-carboxamide; m.p. 247-249°C (Compound 66) .

(111) N- (5-Methoxypyrid-3-yl) -8-0x0-6, 7, 8 , 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide; m.p. 265-267°C (d) (Compound 67) .

^■92- (mmm) N- (1 -Naphthyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1, 2- a:3' , 4' -d] imidazole-9-carboxamide; m.p. 296°C (d) (Compound

68) .

(nnn) N- (2-Naphthyl) -8-0x0-6, 7, 8 , 10-4H-dipyrido [1, 2- a : 3 ' , 4 ' -d] imidazole-9-carboxamide; m.p. 289°C (d) (Compound

69) .

(000) N- (2 -Fluorophenyl) -8-0x0-6, 7,8, 10-4H- dipyrido [1, 2-a:2 ', 3 ' -d] imidazole- 9 -carboxamide, m.p 281- 283° (Compound 70) .

(ppp) N- (2-Fluorobenzyl) -8-0x0-6, 7,8, 10-4H- dipyrido [1, 2 -a:2' , 3 ' -d] imidazole- 9 -carboxamide, m.p 213- 215° (Compound 71) .

(qqq) N- (2-Fluorobenzyl) -8-oxo-10-methyl-6 , 7,8, 10-4H- dipyrido [1, 2-a:2 ' , 3 ' -d] imidazole-9-carboxamide, m.p 230-233° (Compound 72) .

(rrr) N- (2 , 4-Difluorophenyl) -8-0x0-6, 7, 8, 10-4H- dipyrido [1, 2-a:2' , 3' -d] imidazole-9-carboxamide, m.p 281-284' (Compound 73) .

^■93* (sss) N- (4 -Chloro-2-fluorophenyl) -8-0x0-6 , 7, 8 , 10-4H- dipyrido [l,2-a:2' ,3' -d] imidazole-9-carboxamide, m.p 301-304° (Compound 74) .

(ttt) N- (2 -Fluorophenyl) -8-oxo-10-methyl-6, 7 , 8 , 10-4H- dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide, m.p 222-224° (Compound 75) .

(uuu) N- [3- (Dimethylaminomethyl) phenyl] -8-oxo- 6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide, m.p 218-220° (Compound 76) .

(wv) (S) -N- (1-Naphth-l-ylethyl) -8-0x0-6, 7, 8 , 10-4H- dipyrido [l,2-a:2' ,3' -d] imidazole-9-carboxamide, m.p 205-210° (Compound 77) .

(www) N- (2-Fluorobenzyl) -8-oxo-lO- (2- dimethylaminoethyl) -6, 7, 8 , 10-4H-dipyrido [1, 2-a :2 ' ,3' - d] imidazole- 9-carboxamide (Compound 78).

(xxx) N- [2-Fluoro-5- (morpholin-4-ylmethyl) phenyl] -8- oxo-6, 7,8, 10-4H-dipyrido [l,2-a:2' , 3 ' -d] imidazole- 9 -carboxamide hydrochloride, m.p 254-256° (d) (Compound 79) .

-94* (yyy) N- [2-Fluoro-5- (pyrrolidin-l-ylmethyl) phenyl] -8- oxo-6, 7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole- 9-carboxamide hydrochloride, m.p 251-254° (d) (Compound 80) .

(zzz) N-{2-Fluoro-5- [1- (4-methylpiperazin-l- yl) methyl] phenyl} -8-oxo-6,7, 8, 10-4H-dipyrido [1, 2 -a: 2 ' ,3' - d] imidazole- 9 -carboxamide, m.p 240-243° (Compound 81).

(aaaa) N- [2-Fluoro-5- (dimethylaminomethyl) phenyl] -8- oxo-6, 7,8, 10-4H-dipyrido [l,2-a:2' , 3' -d] imidazole- 9-carboxamide hydrochloride, m.p 234-237° (d) (Compound 82).

(bbbb) N- [2-Fluoro-4- (morpholin-4-ylethoxy) phenyl] -8- oxo-6, 7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole- 9- carboxamide, m.p 180-185° (Compound 83) .

(cccc) N- [2-Fluoro-4- (morpholin-4-ylmethyl) phenyl] -8- oxo-6, 7,8, 10-4H-dipyrido [1, 2 -a: 2 ' , 3 ' -d] imidazole- 9- carboxamide, m.p 203-205° (Compound 84) .

(dddd) N-{2-Fluoro-4- [2- (piperidin-1- yl) ethoxy] phenyl} -8-0x0-6, 7, 8, 10-4H-dipyrido [l,2-a:2',3' d] imidazole- 9 -carboxamide, m.p 202-205° (Compound 85).

^■95* (eeee) N- (2-Fluoro-5- { [2- (piperidin-1- yDethoxy] me hyl}phenyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1, 2- a:2' , 3' -d] imidazole- 9-carboxamide , m.p 206-210° (Compound 86)

(ffff) N- (2-Fluoro-5-{ [2-

(dimethylamino) ethoxy] methyl}phenyl) -8-0x0-6, 7,8, 10-4H- dipyrido [l,2-a:2' , 3' -d] imidazole-9-carboxamide, m.p 247-249° (Compound 87) .

(gggg) N- [2-Fluoro-4- (pyrrolidin-l-ylmethyl) phenyl] -8 oxo-6, 7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide, m.p 228-230° (Compound 88) .

(hhhh) N- [2- (2 -Dimethylaminoethoxy) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido [1, 2 -a: 2 ' , 3 ' -d] imidazole-9-carboxamide hydrochloride (Compound 89) .

(iiii) N- [2-Fluoro-5- (piperidin-1-ylmethyl) benzyl] -8- oxo-6, 7,8, 10-4H-dipyrido [1, 2 -a: 2 ' , 3 ' -d] imidazole-9- carboxamide, m.p 118-121° (Compound 90) .

(j j j j ) N- [2-Fluoro-5- (morpholin-4-ylmethyl) benzyl] -8- oxo-6 , 7,8, 10 -4H-dipyrido [1 , 2 -a : 2 ' , 3 ' -d] imidazole-9- carboxamide, m.p 157-159° (Compound 91) .

-96- (kkkk) N- [2-Fluoro-5- (piperazin-1-ylmethyl) phenyl] -8- oxo-6,7, 8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide dihydrochloride, m.p 251-255° (d) (Compound 92).

(1111) N-{2-Fluoro-5-[2-(morpholin-4- ylethoxy) methyl] phenyl } -8-oxo-6 , 7,8, 10-4H-dipyrido [1,2- a:2' , 3' -d] imidazole-9-carboxamide, m.192-194° (Compound 93).

(nnnn) N- {2-Fluoro-5- [bis (2- methoxyethyl) amino] methylphenyl } -8-oxo-6 , 7,8, 10-4H- dipyrido [l,2-a:2' , 3' -d] imidazole-9-carboxamide, m.p 141-143° (Compound 94) .

(oooo) N- (2-Fluorobenzyl) -8-oxo-10-cyclopropylmethyl- 6,7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole- 9-carboxamide, m.p 205-207° (Compound 95) .

(PPPP) ^N_ (2-Fluorobenzyl) -8-oxo-10- (2 -methoxyethyl) - 6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide, m.p 175-177° (Compound 96) .

(qqqq) N- (2-Fluorobenzyl) -8-oxo-10-ethyl-6 , 7, 8, 10-4H- dipyrido [1, 2-a:2' ,3'-d] imidazole-9-carboxamide, m.pl44-146° (Compound 97) .

■97- ( rrrr) N- [3 - (2 -morphol in-4 -ylethoxy) phenyl ] - 8 -oxo-

6 , 7 , 8 , 10 -4H- dipyrido [l,2-a:2' , 3' -d] imidazole-9-carboxamide, m.p 214-216° (Compound 98) .

(ssss) N- [4- (2 -Propylaminoethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide, m.260-262° (Compound 99) .

(tttt) N- [2-Fluoro-4- (2-dimethylaminoethoxy) benzyl] -8- oxo-6, 7,8, 10-4H-dipyrido[l,2-a:2' , 3' -d] imidazole- 9- carboxamide, m.p 97-100° (Compound 100).

(uuuu) N- [2-Fluoro-4- (3 -dimethylaminopropoxy) benzyl] - 8-0x0-6, 7,8, 10-4H-dipyrido [1 , 2 -a : 2 ' ,3' -d] imidazole-9- carboxamide, m.p 86-89° (Compound 101) .

(ww) N-{2-Fluoro-5- [2- (piperazin-1- ylethoxy) methyl] phenyl }-8-oxo-6, 7,8, 10-4H-dipyrido [1,2- a:2' , 3' -d] imidazole- 9-carboxamide, m.p 220-223° (Compound 102).

(wwww) N- [2-Fluoro-4- (2 -ethylaminoethoxy) phenyl] -8- oxo-6, 7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide hydrochloride, m.281-283° (d) (Compound 103).

^■98- (xxxx) N- [ (2-Ethylaminoethoxy) -5-pyridyl] -8-oxo- 6,7, 8,10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide dihydrochloride, m.p 261-263° (d) (Compound 104).

(yyyy) N- [4- (2 -Isopropylaminoethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide hydrochloride, m.279-281° (d) (Compound 105).

(zzzz) N- [4- (2 -Ethylaminoethoxy) phenyl] -8-oxo- 6, 7, 8, 10-4H-dipyrido [l,2-a:2' , 3' -d] imidazole-9-carboxamide hydrochloride, m.p 283-285° (d) (Compound 106).

(aaaaa) N- [3-Fluoro-4- (2-propylaminoethoxy) phenyl] -8- oxo-6, 7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide hydrochloride, m.282-285° (d) (Compound 107).

(bbbbb) N- [4- (3 -Propylaminopropoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:2' , 3 ' -d] imidazole-9-carboxamide hydrochloride, m.265-268° (d) (Compound 108).

(ccccc) N-{2-Fluoro-4- [2- (piperidin-1- yDethoxy] phenyl} -8-0x0-6, 7,8, 10-4H-dipyrido [1, 2 -a: 3 ' ,4' - d] imidazole- 9 -carboxamide; m.p. 177-180° C (Compound 109)

^•99- (ddddd) N-{ [2-Fluoro-4- (morpholin-4-ylethoxy) ] phenyl} - 8-oxo-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide ; m.p. 176-177° C (Compound 110) .

(eeeee) N- { [2-Fluoro-4- (2-ethylaminoethoxy) ] phenyl} -8- oxo-6, 7,8,10-4H-dipyrido [1, 2-a :3 ' , 4 ' -d] imidazole-9-carboxamide dihydrochloride; m.p. 199-205° C (Compound 111) .

(fffff) N-{ [2-Fluoro-4- (pyrrolidin-1-ylmethyl) ] phenyl} - 8-0x0-6, 7, 8, 10-4H-dipyrido [l,2-a:3' ,4' -d] imidazole-9- carboxamide; m.p. 195-197° C (Compound 112) .

(ggggg) N- { [2-Fluoro-4- (morpholin-4-ylmethyl) ] phenyl } - 8-oxo-6,7, 8, 10-4H-dipyrido[l, 2-a: 3' , 4 ' -d] imidazole-9- carboxamide; m.p. 239-240° C (Compound 113) .

(hhhhh) N-{ [2-Fluoro-5-(N,N- dimethylaminomethyl) ] phenyl} -8-oxo-6, 7,8, 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole-9-carboxamide; m.p. 201-203° C (Compound 114) .

(iiiii) N-{ [2-Fluoro-5- (pyrrolidin-1-ylmethyl) ] phenyl } - 8-0x0-6, 7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9- carboxamide ; m.p. 136-140° C (Compound 115) .

^■100- (j j j j j) N-{2-Fluoro-5- [2- (piperazin-1-yl) methyl] phenyl} -8-0x0-6, 7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide tris (trifluoroacetate) ; m.p. 91-97° C (Compound 116) .

(kkkkk) N-{ [2-Fluoro-5- (dimethylaminoethoxymethyl) ] phenyl } -8-oxo-6, 7, 8, 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide; m.p. 157-158° C (Compound 117) .

(11111) N-{2-Fluoro-5- [2- (piperidin-1- yl) ethoxy] phenyl }-8-oxo-6, 7,8, 10-4H-dipyrido [1, 2-a: 3 ' ,4' - d] imidazole-9-carboxamide; m.p. 142-144° C (Compound 118).

(mmmmm) (R) -N- [4- (Pyrrolidin-2-ylmethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [1, 2-a:3 ' ,4' -d] imidazole- 9-carboxamide dihydrochloride; m.p. 254-258° C (Compound 119) .

(nnnnn) (S) -N- [4- (Pyrrolidin-2 -ylmethoxy) phenyl] -8-oxo- 6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide dihydrochloride; m.p. 258-260° C (Compound 120) .

(ooooo) N- [4- (Piperid-3 -ylmethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide dihydrochloride; m.p. 248-250° C (Compound 121)

^■101* (ppppp) N- [4- (2 -Piperid-2-ylethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide dihydrochloride; m.p. 250-252° C (Compound 122) .

(q qq) N- [4- (2 -Ethylaminoethoxy) phenyl] -8-oxo-

6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide dihydrochloride; m.p. 266-268° C (Compound 123) .

(rrrrr) N- [4- (2 -Propylaminoethoxy) phenyl] -8-oxo- 6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide dihydrochloride; m.p. 250-251° C (Compound 124) .

(sssss) N- [4- (2 -Isopropylaminoethoxy) phenyl] -8-oxo- 6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide dihydrochloride; m.p. 247-251° C (Compound 125) .

(ttttt) N- [4- (2-Butylaminoethoxy-phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide dihydrochloride; m.p. 212-215° C (Compound 126) .

(uuuuu) N- [4- (2-tert-Butylaminoethoxy) phenyl] -8-oxo- 6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9 -carboxamide dihydrochloride; m.p. 249-250° C (Compound 127) .

•102- (vww) N- [3-Fluoro-4- (2 -propylaminoethoxy) phenyl] -8- oxo-6, 7,8, 10-4H-dipyrido [l,2-a:3' ,4'-d] imidazole-9-carboxamide dihydrochloride; m.p. 251-253° C (Compound 128) .

(wwwww) N- [2-Methyl-4- (2-propylaminoethoxy) phenyl] -8- oxo-6, 7,8, 10-4H-dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide dihydrochloride; m.p. 255-257° C (Compound 129) .

(xxxxx) N- [2-Fluoro-4- (2 -dimethylaminoethoxy) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide ; m.p. 161-163° C (Compound 130) .

(yyyyy) N- {2 -Fluoro-5 - [ (4-methylpiperizin-1- yl) methyl] benzyl} -8-0x0-6, 7, 8, 10-4H-dipyrido [1, 2-a: 3 ' ,4' - d] imidazole-9-carboxamide ; m.p. 165-167° C (Compound 131).

(zzzzz) N- [2-Fluoro-4- (pyrrolidin-1-ylmethyl) benzyl] -8- oxo-6, 7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide ; m.p. 177-179° C (Compound 132) .

(aaaaaa) N- [2-Fluoro-5- [ (pyrrolidin-1-ylmethyl) benzyl] 8-oxo-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide; m.p. 165-167° C (Compound 133) .

^■103* (bbbbbb) N- (2-Fluorobenzyl) -8-oxo-10- [2- (morpholin-4- yl) ethyl] -6,7,8, 10-4H-dipyrido [1 , 2-a : 3 ' , 4 ' -d] imidazole-9- carboxamide ; m.p. 61-65° C (Compound 134) .

(cccccc) N- (2-Fluorobenzyl) -8-oxo-10- (2- methylaminoethyl) -6,7,8, 10-4H-dipyrido [1, 2-a: 3 ' ,4' - d] imidazole-9-carboxamide; m.p. 155-156° C (Compound 135).

(dddddd) N- (2 -Fluorophenyl) -8-oxo-10- (2- methylaminoethyl) -6,7,8, 10-4H-dipyrido [1, 2-a: 3 ' ,4' - d] imidazole- 9-carboxamide ; m.p. 186-187° C (Compound 136).

(eeeeee)N- [4- (3 -Butylaminopropoxy) phenyl] -8-oxo-6, 7, 8, 10- 4H-dipyrido [l,2-a:2' , 3' -d] imidazole- -carboxamide hydrochloride, m.p. 262-264° (d) (Compound 137).

(ffffff) N- [4- (2- (Butylamino)ethoxy) phenyl) ] -8-oxo- 6,7,8, 10-4H-dipyrido [1, 2 -a: 2 ' , 3 ' -d] imidazole-9-carboxamide hydrochloride, m.p. 250-254° (d) (Compound 138).

(gggggg) N- [3- (2 -Propylaminoethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:2' , 3' -d] imidazole-9-carboxamide hydrochloride, m.p 244-247° (d) (Compound 139).

^■104* (hhhhhh) N- [4- (2 -Cyclopropylaminoethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [1 , 2-a : 2 ' , 3 ' -d] imidazole-9-carboxamide hydrochloride, m.p. 180-185° (d) (Compound 140).

(iiiiii) N- [2- (2- (Butylamino) ethoxy) -5-pyridyl] -8-oxo- 6,7,8, 10-4H-dipyrido [1 , 2 -a : 2 ' , 3 ' -d] imidazole-9-carboxamide dihydrochloride, m.p. 272-276° (d) (Compound 141) .

⁽j j j j j j ⁾ N- (2 -Fluorophenyl) -8-oxo-10- (2- dimethylaminoethyl) -6,7,8, 10-4H-dipyrido [1, 2-a: 2 ' ,3' - d] imidazole-9-carboxamide, m.p. 173-175° (Compound 142).

(kkkkkk) N- (2-Fluorophenyl) -8-oxo-10- (2- (ethylamino) ethyl) -6, 7, 8 , 10-4H-dipyrido [1, 2-a :2 ' ,3' - d] imidazole-9-carboxamide, m.p. 241-243° (d) (Compound 143).

N- [2-Fluoro-4- (2 -Propylaminoethoxy) phenyl] -8- oxo-6,7,8,10-4H-dipyrido [l,2-a:2' ,3' -d] imidazole-9-carboxamide hydrochloride, m.p. 260-265° (d) (Compound 144).

(mmmmmm) N- [3- (2- (Butylamino) ethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide hydrochloride (Compound 145) .

(nnnnnn) N- (2-Fluorobenzyl) -8-oxo-10- (3- dimethylaminopropyl) -6,7,8, 10-4H-dipyrido [1 , 2-a :2 ' ,3' -

-105- d] imidazole-9-carboxamide hydrochloride, m.p. 209-213° (d) (Compound 146) .

(oooooo) (R) -N- [4- (Pyrrolidin-2-ylmethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide hydrochloride, m.p. 208-213° (d) (Compound 147) .

(PPPPPP) (S) -N- [4- (Pyrrolidin-2 -ylmethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide hydrochloride, m.p. 215-218° (d) (Compound 148) .

( q qqq) ) ^N_ t^4_ (2-t-Butylaminoethoxy)phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:2' ,3'-d] imidazole-9-carboxamide hydrochloride, m.p. 214-217° (d) (Compound 149).

(rrrrrr) N- [4- (2- (Propylamino) ethoxy) phenyl] -8-oxo-10- methyl-6, 7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9- carboxamide hydrochloride (Compound 150) .

(ssssss) N- [4- (2 -Isobutylaminoethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [1, 2 -a: 2 ' , 3 ' -d] imidazole-9-carboxamide hydrochloride, m.p. 272-276° (d) (Compound 151).

(tttttt) N- [2-Fluoro-4- (2- (dimethylamino) ethoxy) benzyl] - 8-oxo-10-methyl-6,7,8,10-4H-dipyrido[l,2-a:2' , 3 ' -d] imidazole- 9-carboxamide hydrochloride (Compound 152) .

-106- (uuuuuu) N- [2-Fluoro-4- (2 -hydroxyethoxy) benzyl] -8-oxo- 10-methyl-6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide, m.p. 202-205° (Compound 153).

(www) N- [2-Fluoro-4- (2 -propylaminoethoxy) benzyl] -8- oxo-10-methyl-6,7,8,10-4H-dipyrido[l,2-a:2' , 3 ' -d] imidazole-9- carboxamide hydrochloride (Compound 154) .

(wwwwww) N-{2-Fluoro-4- [2- (morpholin-4- yl) ethoxy] benzyl } -8-oxo-10-ethyl -6, 7,8, 10-4H-dipyrido [1 , 2- a:2' , 3' -d] imidazole-9-carboxamide (wax) (Compound 155).

(xxxxxx) N-{4- [2- (Morpholin-4-yl) ethoxy] benzyl} -8-oxo- 10-ethyl-6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole- 9- carboxamide (wax) (Compound 156) .

(yyyyyy) N- {3- [2- (Piperidin-l-yl) ethoxy] benzyl} -8-oxo- lO-ethyl-6,7,8, 10-4H-dipyrido [1, 2-a :2 ' ,3' -d] imidazole-9- carboxamide (wax) (Compound 157) .

(zzzzzz) N- [4- (2 -Propylaminoethoxy) benzyl] -8-oxo-10- ethyl-6, 7, 8, 10-4H-dipyrido [l,2-a:2' , 3' -d] imidazole-9- carboxamide (wax) (Compound 158) .

-107* (aaaaaaa) N- [4- (2 -Isobutylaminoethoxy) benzyl] -8-oxo-10- ethyl -6,7,8, 10-4H-dipyrido [1 , 2 -a : 2 ' , 3 ' -d] imidazole-9- carboxamide (Compound 159) .

(bbbbbbb) N- [2-Fluoro-4- (2 -propylaminoethoxy) benzyl] -8- oxo-10-propyl-6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide (Compound 160) .

(ccccccc) N- [2-Fluoro-4- (2 -Isobutylaminoethoxy) benzyl] -8- oxo-10-propyl-6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide (Compound 161) .

(ddddddd) N- [2-Fluoro-4- (3 -piperidin-1-ylpropoxy) benzyl] - 8-oxo-10-ethyl-6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide) (Compound 162) .

(eeeeeee) N- [2-Fluoro-4- (2 -propylaminoethoxy) benzyl] -8- oxo-10-ethyl-6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide) (Compound 163) .

(fffffff) N- [2-Fluoro-4- (2 -isopropylaminoethoxy) benzyl] - 8-oxo-10-ethyl-6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole- 9- carboxamide (Compound 164).

^■108- (9999999) N- [2-Fluoro-4- (2 -isoamylaminoethoxy) benzyl] -8- oxo-10-ethyl -6, 7, 8, 10-4H-dipyrido [1, 2 -a: 2 ' ,3' -d] imidazole-9- carboxamide (Compound 165) .

(hhhhhhh) N- [4- (2 -Cyclopropylmethylaminoethoxy) phenyl] -8- oxo-6, 7,8, 10-4H-dipyrido [l,2-a:2' ,3' -d] imidazole-9-carboxamide hydrochloride (Compound 166) .

(iiiiiii) N- [4- (3 -Ethylaminopropoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide hydrochloride, m.p. 260-262° (Compound 167) .

(jjjjjjj) N-[4- (3-Butylaminopropoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide hydrochloride, m.p. 185-190° (Compound 168) .

(kkkkkkk) N- [3- (2 -Propylaminoethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide hydrochloride, m.p. 245-247° (Compound 169) .

N- [4- (2 -Cyclopropylaminoethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [1,2 -a: 3' ,4' -d] imidazole- 9-carboxamide hydrochloride, m.p. 255-256° (Compound 170) .

^■109- (mmmmmmm) N- [2- (2- (Ethylamino) ethoxy) pyrid-5-yl] -8-oxo- 6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide hydrochloride, m.p. 237-239° (Compound 171) .

(nnnnnnn) N- [2- (2- (Butylamino) ethoxy) pyrid-5-yl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide hydrochloride, m.p. 177-181° (Compound 172) .

(ooooooo) N- [4- (2-Isobutylaminoethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3' ,4'-d] imidazole-9-carboxamide hydrochloride (Compound 173) .

(ppppppp) N- (2-Ethoxypyrid-5-yl) -8-oxo-6, 7, 8, 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide hydrochloride, m.p. 214° (d) (Compound 174).

( q qq ) ^N~ [2-Fluoro-4- (3 -dimethylalminopropoxy) benzyl] - 8-oxo-10-ethyl-6, 7,8, 10-4H-dipyrido [1, 2-a : 3 ' , 4 ' -d] imidazole-9- carboxamide) (Compound 175) .

(rrrrrrr) N- [2-Fluoro-4- (2 -morpholin-4-ylethoxy) benzyl] - 8-oxo -6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide) , m.p. 137-140° (Compound 176) .

^■110* (sssssss) N- [2-Fluoro-4- (2-piperidin-1-ylethoxy) benzyl] - 8-oxo -6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide) , m.p. 140-143° (Compound 177) .

(ttttttt) N- [2-Fluoro-4- (3-piperidin-l-ylpropoxy) benzyl] - 8-oxo -6, 7, 8, 10-4H-dipyrido [l,2-a:3 ' ,4' -d] imidazole-9- carboxamide) , m.p. 55-56° (Compound 178) .

(uuuuuuu) N- [2-Fluoro-4- (2-dimethylaminoethoxy) benzyl] -8- oxo-10-ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide (Compound 179) .

(vwvwv) N- [ 4- (3-Dimethylaminopropoxy) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide) , m.p. 146-148° (Compound 180) .

(wwwwwww) N- [ 4- (2-Dimethylaminoethoxy) benzyl] -8-oxo 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide) , m.p. 201-203° (Compound 181) .

(xxxxxxx) N- [4- (2-Pyrrolidin-l-ylethoxy) benzyl] -8-oxo 6,7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide) , m.p. 55-57° (Compound 182) .

•Ill- (yyyyyyy) N- [4- (3 -Pyrrolidin- 1-ylpropoxy) benzyl] -8-oxo 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide) , m.p. 148-152° (Compound 183) .

(zzzzzzz) N- [4- (4 -Pyrrolidin- 1-ylbutoxy) benzyl] -8-oxo 6,7,8, 10-4H-dipyrido [1, 2-a: 3 ' , 4 ' -d] imidazole- 9-carboxamide) , m.p. 137-140° (Compound 184) .

(aaaaaaaa) N- [2-Fluoro-4- (2-piperidin-l- ylethoxy) benzyl] -8-oxo-10-ethyl-6, 7, 8 , 10-4H-dipyrido [1,2- a:3' , 4' -d] imidazole- 9-carboxamide (Compound 185).

(bbbbbbbb) N- [2-Fluoro-4- (2-morpholin-4- ylethoxy) benzyl] -8-oxo-10-ethyl-6, 7,8, 10-4H-dipyrido [1,2- a:3' , 4' -d] imidazole-9-carboxamide (Compound 186).

(cccccccc) N- [4- (2 -dimethylaminoethoxy) benzyl] -8-oxo- 10-ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9- carboxamide (Compound 187) .

(ddddddddd) N- [4- (4-Pyrrolidin-l-ylbutoxy) benzyl] -8- oxo-10-ethyl-6, 7,8, 10-4H-dipyrido [1, 2- : 3 ' , 4 ' -d] imidazole-9- carboxamide (Compound 188) .

^■112* (eeeeeeee) N- [2-Fluoro-4- (3 -pyrrolidin-1- ylpropoxy) benzyl] -8-oxo -6,7, 8 , 10-4H-dipyrido [1, 2-a: 3 ' ,4' - d] imidazole-9-carboxamide, m.p. 125-130° (Compound 189).

(ffffffff) N- [3- (2 -Morpholin-4 -ylethoxy) benzyl] -8-oxo -6,7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide, m.p. 186-190° (Compound 190) .

(gggggggg) N- [3- (3 -Piperidin-1-ylpropoxy) benzyl] -8- oxo -6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide, m.p. 129-131° (Compound 191).

(hhhhhhhh) N- [4- (2-Morpholin-4-ylethoxy) benzyl] -8-oxo -6,7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide, m.p. 184-185° (Compound 192) .

(iiiiiiii) N- [4- (2- (l-Methylpyrrolidin-2- yl) ethoxy) benzyl] -8-oxo -6,7,8, 10-4H-dipyrido [1 , 2-a : 3 ' ,4' - d] imidazole-9-carboxamide, m.p. 160° (d) (Compound 193).

(jjjjjjjj) N- [3- (2 -Piperidin-1-ylethoxy) benzyl] -8 -oxo -6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide, m.p. 175-176° (Compound 194) .

^■113* ⁽kkkkkkkk) N- [4- (2-Piperidin-l-ylethoxy) benzyl] -8-oxo -6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide, m.p. 180-181° (Compound 195) .

(11111111) N- [4- (3 -Piperidin-1-ylethoxy) benzyl] -8-oxo -6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide, m.p. 140-143° (Compound 196) .

(mmmmmmmm) N- [2-Fluoro-4- (2-pyrrolidin-l- ylethoxy) benzyl] -8 -oxo-6, 7, 8 , 10-4H-dipyrido [1 , 2-a: 3 ' ,4' - d] imidazole-9-carboxamide, m.p. 155° (d) (Compound 197).

(nnnnnnnn) N- [4- (2-Diethylaminoethoxy) benzyl] -8-oxo - 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide, m.p. 167-168° (Compound 198) .

(oooooooo) N- [3- (2 -Diethylaminoethoxy) benzyl] -8-oxo 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide, m.p. 100-102° (Compound 199) .

(pppppppp) N- [2-Fluoro-4- (3-Piperidin-l- ylpropoxy) benzyl] -8-oxo- 10- (2 -methoxyethoxy) -6,7,8, 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole- 9-carboxamide (Compound 200]

•114* (qqqqqqqq) N- [2-Fiuoro-4- (2-

Dimethylaminoethoxy) benzyl] -8-oxo-10-propyl-6, 7, 8, 10-4H- dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide (Compound 201)

(rrrrrrrr) N- [2-Fluoro-4- (3-

Dimethylaminopropoxy) benzyl] -8-oxo-10-propyl -6, 7, 8, 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide (Compound 202)

(ssssssss) N- [2-Fluoro-4- (2- Dimethylaminoethoxy) benzyl] -8-oxo-10-butyl-6, 7,8, 10-4H- dipyrido [1, 2 -a:3' ,4' -d] imidazole-9-carboxamide (Compound 203)

(tttttttt) N- [2-Fluoro-4- (3- Dimethylaminopropoxy) benzyl] -8 -oxo-10-butyl -6, 7,8, 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole- 9-carboxamide (Compound 204)

(uuuuuuuu) N- [2-Fluoro-4- (3-Piperidin-l- ylpropoxy) benzyl] -8-oxo-10-ethyl-6 , 7,8, 10-4H-dipyrido [1,2- a:3' , 4' -d] imidazole-9-carboxamide (Compound 205).

(vwwwv) N- [2-Fluoro-4- (2-Pyrrolidin-l- ylethoxy) benzyl] -8 -oxo-10 -ethyl-6 , 7,8, 10-4H-dipyrido [1 , 2- a:3' , 4' -d] imidazole- 9-carboxamide (Compound 206).

•115- (wwwwwwww) N- [2-Fluoro-4- (3-Pyrrolidin-l- ylpropoxy) benzyl] -8-oxo-10-ethyl -6, 7, 8 , 10-4H-dipyrido [1, 2- a:3' , 4' -d] imidazole-9-carboxamide (Compound 207).

(xxxxxxxx) N- [3- (2 -Piperidin-1-ylethoxy) benzyl] -8- oxo-10-ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide (Compound 208) .

(yyyyyyyy) N- [2-Fluoro-4- (2 -Pyrrolidin- 1- ylethoxy) benzyl] -8-oxo-10-propyl-6, 7, 8, 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole-9-carboxamide (Compound 209).

(zzzzzzzz) N- [2-Fluoro-4- (3 -Pyrrolidin-1- ylpropoxy) benzyl] -8-oxo-10-propyl-6, 7,8, 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole-9-carboxamide (Compound 210).

(aaaaaaaaa) N- [4- (2-Piperidin-l-ylethoxy) benzyl] -8- oxo-10-ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9- carboxamide (Compound 211) .

(bbbbbbbbb) N- [4- (2 -Diethylaminoethoxy) benzyl] -8-oxo- 10-ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9- carboxamide (Compound 212) .

^■116- (ccccccccc) N- [4- (3 -Piperidin-1-ylpropoxy) benzyl] -8- oxo-10-ethyl-6, 7, 8 , 10-4H-dipyrido [1, 2-a: 3 ' , 4 ' -d] imidazole-9- carboxamide (Compound 213) .

(ddddddddd) N- [4- (2 -Isobutylaminoethoxy) benzyl] -8-oxo- 10-ethyl-6,7,8,10-4H-dipyrido[l,2-a:2' , 3 ' -d] imidazole-9- carboxamide (Compound 214) .

(eeeeeeeee) N- [2-Fluoro- (2 -propylaminoethoxy) benzyl] - 8-oxo-10-propyl-6, 7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole- 9-carboxamide (Compound 215) .

(fffffffff) N- [2-Fluoro-4- (2- isobutylaminoethoxy) benzyl] -8-oxo-10-propyl-6, 7,8, 10-4H- dipyrido [1, 2-a:2' , 3 ' -d] imidazole-9-carboxamide (Compound 216)

( gggg ggg) ^N_ [2-Fluoro-4- (3-piperidinopropyl) benzyl] -8 -oxo-10 -ethyl-6, 7, 8, 10-4H-dipyrido [1, 2 -a: 2 ' ,3' - d] imidazole-9-carboxamide (Compound 217).

(hhhhhhhhh) N- [2-Fluoro-4- (2- propylaminoethoxy) benzyl] -8 -oxo- 10 -ethyl -6, 7,8, 10-4H- dipyrido [l,2-a:2' , 3' -d] imidazole-9-carboxamide (Compound 218)

^■117- (iiiiiiiii) N- [2-Fluoro-4- (2- isopropylaminoethoxy) benzyl] -8-oxo-10-ethyl-6, 7,8, 10-4H- dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide (Compound 219),

(jjjjjjjjj) N- [2-Fluoro-4- (2- isobutylaminoethoxy) benzyl] -8 -oxo-10-ethyl-6, 7,8, 10-4H- dipyrido [1,2 -a: 2' ,3' -d] imidazole-9-carboxamide (Compound 220)

(kkkkkkkkk) N- [4- (2 -Cyclopropylaminoethoxy) phenyl] -8- oxo -6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide (Compound 221) .

(111111111) N- (2 -Fluorophenyl) -3- (2- hydroxyethoxy) -8-oxo -6, 7,8, 10-4H-dipyrido [l,2-a:3' ,4' - d] imidazole-9-carboxamide (Compound 222).

(mmmmmmmmm) N- (2-Fluorobenzyl) -3- (2 -hydroxyethoxy) -8- oxo -6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide (Compound 223) .

(nnnnnnnnn) N- (2 -Fluorophenyl) -3- (2- propylaminoethoxy) -8-oxo -6,7,8, 10-4H-dipyrido [l,2-a:3' ,4' d] imidazole-9-carboxamide (Compound 224) .

^■118- (ooooooooo) N- [2- (2- (Butylamino) ethoxy) -5-pyridyl] -8- oxo-6, 7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide (Compound 225) .

EXAMPLE 4

The pharmaceutical utility of compounds of this invention is indicated by the following assay for GABAa receptor binding activity. Assays are carried out as described in Thomas and Tallman (J. Bio. Chem. 156.: 9838-9842 , J. Neurosci. 2: 433-440, 1983) . Rat cortical tissue is dissected and homogenized in 25

volumes (w/v) of 0.05 M Tris HCl buffer (pH 7.4 at 4°C) . The

tissue homogenate is centrifuged in the cold (4°) at 20,000 x g for 20'. The supernatant is decanted and the pellet is rehomogenized in the same volume of buffer and again centrifuged at 20,000 x g. The supernatant is decanted and

the pellet is frozen at -20°C overnight. The pellet is then thawed and rehomogenized in 25 volume (original wt/vol) of buffer and the procedure is carried out twice. The pellet is finally resuspended in 50 volumes (w/vol of 0.05 M Tris HCl

buffer (pH 7.4 at 40°C) .

Incubations contain 100 ml of tissue homogenate, 100 ml

of radioligand 0.5 nM (³H-R015-1788 [³H-Flumazenil] specific activity 80 Ci/mmol) , drug or blocker and buffer to a total

-119- volume of 500 ml. Incubations are carried for 30 min at 4°C then are rapidly filtered through GFB filters to separate free and bound ligand. Filters are washed twice with fresh 0.05 M

Tris HCl buffer (pH 7.4 at 4°C) and counted in a liquid scintillation counter. 1.0 mM diazepam is added to some tubes to determine nonspecific binding. Data are collected in triplicate determinations, averaged and % inhibition of total specific binding is calculated. Total Specific Binding = Total - Nonspecific. In some cases, the amounts of unlabeled drugs is varied and total displacement curves of binding are carried out. Data are converted to Ki's. Compounds of this invention when tested in this assay generally have Ki's of

less than 1 μM.

In addition, the following assay may be used to determine if the compounds of the invention are agonists, antagonists, or inverse agonists, and, therefore, their specific pharmaceutical utility. The following assay can be employed to determine specific GABAa receptor activity. Assays are carried out as described in White and Gurley (NeuroReport 6_: 1313-1316, 1995) and White, Gurley, Hartnett, Stirling, and Gregory (Receptors and Channels 3 : 1-5, 1995) with modifications. Xenopus Laevis oocytes are enzymatically isolated and injected with non-polyadenylated cRNA mixed in a

ratio of 4:1:4 for human derived α, β and γ subunits,

-120- respectively. For each subunit combination, sufficient message is injected to result in current amplitudes of >10 nA when 1 μM GABA is applied.

Electrophysiological recordings are carried out using the two electrode voltage-clamp technique at a membrane holding potential of -70 mV.

Compounds are evaluated against a G7ABA concentration that evokes <10% of the maximal evokable GABA current. Each oocyte is exposed to increasing concentrations of compound in order to evaluate a concentration/effect relationship. Compound efficacy is expressed as a percent-change in current amplitude: 100* ( (Ic/I) -1) , where Ic is the GABA evoked current amplitude observed in the presence of compound and I is the GABA evoked current amplitude observed in the absence of compound.

Specificity of a compound for the R015-1788 site is determined following completion of the concentration/effect curve. After washing the oocyte sufficiently to remove previously applied compound, the oocyte is exposed to GABA + 1 μM R015-1788, followed by exposure to GABA + 1 μM R015-1788 + compound. Percent change due to addition of compound is calculated as described above. Any percent change observed in the presence of R015-1788 is subtracted from the percent changes in current amplitude observed in the absence of 1 μM R015-1788. These net values are used for the calculation of average efficacy and EC_S0 values .

-121- To evaluate average efficacy and EC₅₀ values, the concentration/effect data are averaged across cells and fit to the logistic equation. Average values are reported as mean + standard error.

The invention and the manner and process of making and using it, are now described in such full, clear, concise and exact terms as to enable any person skilled in the art to which it pertains, to make and use the same. It is to be understood that the foregoing describes preferred embodiments of the present invention and that modifications may be made therein without departing from the spirit or scope of the present invention as set forth in the claims. To particularly point out and distinctly claim the subject matter regarded as invention, the following claims conclude this specification.

•122*

Claims

WHAT IS CLAIMED IS :

1 . A compound of the formula :

R o _G

or a pharmaceutically acceptable non-toxic salt thereof wherein:

V

represents a nitrogen-containing ring system which is optionally substituted with up to two groups independently selected from halogen, or R³R⁴N- ; R²0Y- wherein Y is d-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or

Cι-C₆ alkoxy or Cι-C₆ alkyl, each of which is optionally substituted on its alkyl portion with -

NR³R⁴ , where

R³ and R⁴ are the same or different and represent hydrogen, Ci-C₆ alkyl , or C₃-C₇ cycloalkyl , Ci- C₆ alkylamino (Cι-C₆) alkyl , or Cι-C₆ alkoxy (Ci-

C₆) alkyl ; or

^■ 123 * NR³R⁴ represents a 5, 6, or 7-membered heterocyclic ring, such as for example, imidazolyl, pyrrolidinyl, morpholinyl, N-unsubstituted or N- (Cι-C₆) alkyl piperazinyl, or piperidinyl.

G is

C₃-C₇ cycloalkyl, Cι-C₆ alkyl optionally substituted with

Cι-C₆ alkoxy, or mono- or di (Cι-C₆) alkylamino; or a group of the formula:

(W)_n

-V v- R¹ where

R¹ is Cι-C₆ alkyl or C₃-C₇ cycloalkyl; a group of the formula :

where s is 1 or 2; and R^k, Rm and Rn independently represent halogen, hydroxy, trifluoromethyl, or Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Cι-C₆) alkylamino; or R¹ is aryl or heteroaryl, each of which is optionally substituted with up to three groups independently selected from halogen, hydroxy, trifluoromethyl , or mono- or di (Cι-C₆) alkylamino;

-124- R²OY- wherein Y and R² are defined as above, and

Y and R², when R² is not hydrogen, are independently optionally substituted with -

NR³R⁴; or Cι-C₆ alkyl or Cι-C_fi alkoxy, each of which is optionally substituted on its alkyl portion with a heterocyclic group or -NR³R⁴ where R³ and R⁴ are as defined above; or Y may be linked through R³ or R⁴ to form a heterocyclic ring;

W represents CR⁵R⁶ where

R⁵ and R⁶ independently represent hydrogen, Cι-C₆ alkyl, C₃-C₇ cycloalkyl, or CR⁵R⁶forms a C₃-C₇ cycloalkyl group; and n is 0, or an integer of from 1-4; and

R represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; or arylalkyl or heteroarylalkyl where each aryl portion is optionally substituted with up to three groups independently selected from halogen, hydroxy, trifluoromethyl , or mono- or di (Cι-C₆) alkylamino; R²OY- where R² and Y are defined as above, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or

•125* Cι-C₆ alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴ where R³ and R⁴ are as defined above, or a heterocyclic group.

2. A compound according to claim 1, which has the formula:

f Zi. •N ^■N ^-κ\ H

or a pharmaceutically acceptable salt thereof wherein:

Zi, Z₂, Z₃, and Z₄ independently represent N or CR⁷, with the proviso that at least one but not more than two of Zi, Z₂, Z₃, and Z₄ represent nitrogen;

R is as defined above for Formula I; R⁷ is hydrogen, halogen, R³R⁴N- , R²OY- wherein Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or

NR³R⁴, alkyl, alkoxy, R³RNY-, or R³RN- , where

Y is as defined above in claim 1; and

^■126- R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; or R³ and R⁴ may be taken together to form a ring; G represents (i) (C₃-C₇) cycloalkyl;

(ii) a group of the formula:

R⁸<\γ- V

where Y is Cι-C₆ alkylene; and R⁸ is hydrogen, lower alkyl, or (C₃-C₇) cycloalkyl;

(iii) a group of the formula:

R⁹R¹⁰ V V where

Y is as defined above for ii; and R⁹ and R¹⁰ are same or different and represent hydrogen, Cι-C₆ alkyl, C₃-C₇ cycloalkyl, Cι-C₆ alkylamino (Cι-C₆) alkyl, or Cι-C₃ alkoxy (Cι-C₆) alkyl ; or

R⁹ and R¹⁰ together with the nitrogen atom to which they are attached form a heterocyclic moiety

of 5, 6, or 7 members such as imidazolyl, pyrrolidinyl, morpholinyl, N-unsubstituted or N- (C_x-

C₆) alkyl piperazinyl, or piperidinyl;

^■127* (iv) a group of the formula

where

R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², -NR³R⁴;

R¹², R^12', and R¹³ are the same or different and represent hydrogen, halogen, trifluoromethyl , -NR³R⁴, hydroxy;

R²OY- wherein Y is Cι-C₆ alkylene and R² represents hydrogen, C_ι-C_e alkyl , or C₃-C₇ cycloalkyl , and Y and R² , when R² is not hydrogen, are independently optionally substituted with NR³R⁴ ;

Cι-C₆ alkoxy or Cι-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

R¹¹ and R¹², or R¹² and R¹³ together with the atoms to which they are attached form an aryl, heteroaryl, or (hetero) cyclic ring; or or Y may be linked through R³ or R⁴ to form a heterocyclic ring; -128- where R², R³, R⁴, Y, R⁹, and R¹⁰ are defined as above ;

(v) a group of the formula:

_RχvA^A₀A where Y, R¹¹ and R¹¹ are defined above; (vi) a group of the formula:

_NR9_R10

where Y, R⁹, R¹⁰, R¹¹, and R^11' are as defined above; (vii) a group of the formula:

R¹¹ YY %R⁹R¹⁰

where Y, R⁹, R¹⁰, R¹¹, R¹¹' , and R¹³ are as defined above ;

(viii) a group of the formula:

NR⁹R¹⁰

^•129- where Y, R^s, R , R , R^1X , and R¹³ are as defined above;

(ix) a group of the formula:

R 11

R 12

.Y •>9r10

/^Y^NR⁹R¹⁰

where each Y, and R⁹, R¹⁰, R¹¹, R^11', and R¹² are as defined above;

(xi) a group of the formula:

R 11

R 12

,O, .NR⁹R¹⁰

R 11

Y^' Y^'

where each Y, R⁹, R¹⁰, R¹¹, R^11' , and R¹² are as defined above ;

(xii) a group of the formula:

^■130-

where R¹¹, R¹², and R¹³ are as defined above respectively, and

(xiii) a group of the formula:

(xiv) a group of the formula: )5

Rv _R6 x where X is (C₃-C₇) cycloalkyl, and

R and R are as defined above;

(xv) a group of the formula:

•131-

where R⁵, R⁶, R¹¹, R¹¹' , R¹², R^12' , and R¹³ are as defined above respectively;

(xvi) a group of the formula:

where Y, R⁵, R⁶, R⁹, R¹⁰, and R¹¹ are as defined above respectively;

(xvii) a group of the formula:

^OR⁸

where R⁵, R⁶, R¹¹, R⁸, and Y are as defined above respectively;

(xviii) a group of the formula :

^■ 132 -

where R⁵, R⁶, R¹¹, R^11' , R¹³, R⁸, and Y are as defined above respectively;

(xix) a group of the formula:

^D11

where R⁵, R⁶, R¹¹, R¹², R⁸, and Y are as defined above respectively;

(xx) a group of the formula:

R¹¹

NR⁹R 10

where R⁵, R⁶, R⁹, R¹⁰, R¹¹, R^11' , R¹³, and Y are as defined above respectively;

-133* where R⁵, R⁶, R⁹, R¹⁰, R¹¹, R¹², and Y are as defined above respectively;

(xxii) a group of the formula:

⁹R¹⁰RN

/ Y

R⁵ R⁶

where R\ R", R^s. R^iU, _R"'_{# R}"_{# R}"_{f and γ are as}

defined above respectively;

(xxiii) a group of the formula:

R⁵R⁶ R 11

,NR⁹R¹⁰

Y

where R¹¹, R¹², R^12', and R¹³ are as defined above respectively;

(xxiv) a group of the formula:

R⁵ _R ⁶ R¹¹

where R⁵, R⁶, R⁹, _R" _RII_{# R}ιr _{# R}i2_{/and γ are as}

defined above respectively;

-134- 092

(xxv) a group of the formula: 13

R¹^ .R^1Z

"^" J where R¹¹, R¹², R^12' , and R¹³ are as defined above respectively;

(xxvi) a group of the formula:

R¹² R¹⁷ where R⁵, R⁶, R¹¹, R^11', R¹², R¹⁴, R¹⁵, R¹⁶, and R¹⁷ are as defined above.

(xxvii) a group of the formula:

where R⁵, R⁶, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R^1S, and R¹⁷ are as defined above respectively;

-135- (xxviii) a group of the formula:

^c Q

where Q represents a heteroaryl group;

(xxix) a group of the formula:

R⁶

^Q where R , R and Q are as defined above; and

(xxx) a group of the formula :

R ,11'

.12'

R

^• _R13

I l 12

where Y, R¹¹, R^11' , R¹², R^12' and R¹³ are as described above .

A compound of the formula:

R 12

13

R r<¹¹ r-,1

R¹

R o

N

N o Rn¹

R⁷- >- ^/

^ H

N ^"N '\ y=_^o

- 136 - or a pharmaceutically acceptable salt thereof wherein R represents

R²OY- where Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; or Cι-C₆ alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; R⁷ is hydrogen, halogen, mono- or di (Cι-C₆) alkylamino, Ci- C₆ alkyl, or C₃-C₇ cycloalkyl; R¹¹, R^11', R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C_β alkyl, Cι-C₆ alkoxy, or mono- or di (Cι-C₆) alkylamino; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, Cι-C₆ alkylamino (Cι-C₆) alkyl, or Cι-C₆ alkoxy (Cι-C₆) alkyl ; or NR³R⁴ represents a 5, 6, or 7-membered heterocyclic ring, such as for example, imidazolyl, pyrrolidinyl, morpholinyl, N-unsubstituted or N- (Cι-C₆) alkyl piperazinyl, or piperidinyl.

4. A compound according to claim 3, wherein R^11' and R^12' are hydrogen and R¹¹, R¹², and R¹³ independently represent hydrogen, halogen, hydroxy, Ci-C₆ alkoxy, or Cι-C₆ alkyl.

^•137-

5. A compound according to claim 1, which has the formula :

^R\ ³

N^' • N -N R 11 " R⁷-r ^,==\ H

N ^:O

wherein R represents

R²0Y- where Y is Cι -C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl , or C₃ -C₇ cycloalkyl , and Y and R² , when R² is not hydrogen, are independently optionally substituted with -NR³R⁴ ; or

Ci-Cg alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; R⁷ is hydrogen, halogen, mono- or di (Cι-C₆) alkylamino, -_.- C₆ alkyl, or C₃-C₇ cycloalkyl;

R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₃ alkyl, -OR², - NR³R⁴ ; R¹², R^12' , and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl , -NR³R⁴;

R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴;

-138- Ci-Cg alkoxy or Cι-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or R¹² and R¹³ together with the atoms to which they are attached form a (hetero) cyclic ring; or Y and R³ or R⁴ together form a 5, 6, or 7-membered heterocyclic ring with one of the alkyl groups of

NR³R⁴,

Y is Ci-Cg alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; and

R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, Cι-C₆ alkylamino (Ci-Cg) alkyl, or C_x-Cg alkoxy (Ci- C₆) alkyl; or NR³R⁴ represents a 5, 6, or 7-membered heterocyclic ring, such as for example, imidazolyl, pyrrolidinyl, morpholinyl, N-unsubstituted or N- (Ci-Cg) alkyl piperazinyl, or piperidinyl.

6. A compound according to claim 5, wherein R^11' and R^12' are hydrogen and R¹¹, R¹², and R¹³ independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkoxy, or Cι-C₆ alkyl.

7. A compound according to claim 5, wherein

-139* R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Ci- C₆) alkylamino,- and

R¹², R^12', and R¹³ are the same or different and represent halogen, Cι-C₆ alkyl, R²OY-, where Y is a bond or Ci-

NR³R⁴.

8. A compound according to claim 5, wherein Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group.

9. A compound according to claim 5, wherein Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or Ci-C alkyl.

10. A compound according to claim 5, wherein R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Ci-C₆ alkoxy, or mono- or di (Cι-C₆) alkylamino; and

R¹², R^12', and R¹³ are the same or different and represent hydrogen, halogen, or Cι-C₆ alkyl substituted on its alkyl portion with -NR³R⁴, provided that at least one of R¹², R^12' , and R¹³ is substituted Cι-C₆ alkyl.

-140-

11. A compound according to claim 1, which has the formula:

R 11' \ R 12'

R O AA

N \\ -^(A)c Λ\ R

R „11 \ -~

R 12

wherein

R²OY- where Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R , when is not hydrogen, are independently optionally substituted with -NR R ; or Ci-Cg alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; R⁷ is hydrogen, halogen, mono- or di (Cι-C_fi) alkylamino, Ci- C₆ alkyl, or C₃-C₇ cycloalkyl;

^■141* R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², - NR³R⁴; R¹², R¹² , and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl , -NR³R⁴;

R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-Cg alkoxy or Ci-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

(hetero) cyclic ring; or

NR³R⁴ ;

Y is Ci-Cg alkylene and R² represents hydrogen, Cι-C₆ alkyl , or C₃-C₇ cycloalkyl ; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₃ alkyl , or C₃ -C₇ cycloalkyl , C_x-C₆ alkylamino (Ci-Cg) alkyl , or Cι-C₆ alkoxy (Ci-

C₆) alkyl ; or

N- (Ci-Cg) alkyl piperazinyl, or piperidinyl. -142-

12. A compound according to claim 11, wherein q is 0 or A is methylene or ethylene.

13. A compound according to claim 12, where R^11' and R^12' are hydrogen and R¹¹, R¹², and R¹³ independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkoxy, or Ci-C₆ alkyl.

14. A compound according to claim 12, where

R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (C_x- C₆) alkylamino; and

R¹², R^12', and R¹³ are the same or different and represent halogen, Cι-C₆ alkyl, R²0Y- , where Y is a bond or Cι-C₆ alkylene and R² is optionally substituted with -NR³R⁴.

15. A compound according to claim 14, where only one of R¹², R^12', and R¹³ is R²0Y- and Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms an optionally substituted morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group optionally substituted with Ci-Cg alkyl.

16. A compound according to claim 15, wherein one of R¹¹ and R^11' is halogen, hydroxy, or Cι-C₆ alkoxy.

-143*

17. A compound according to claim 1, which has the formula :

wherein

R²OY- where Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or Ci-Cg alkyl, Cι-C_e alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; R⁷ is hydrogen, halogen, mono- or di (Cι-C₆) alkylamino, Ci-

C₆ alkyl, or C₃-C₇ cycloalkyl; R¹¹ and R¹¹ are the same or different and are selected from hydrogen, halogen, hydroxy, C_ι-C₆ alkyl, -OR², - NR³R⁴ ;

R , R , and R , 13 are the same or different and represent

^■ 144 - hydrogen, halogen, hydroxy, trifluoromethyl, -NR³R⁴; R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-Cg alkoxy or Cι-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or R¹² and R¹³ together with the atoms to which they are attached form a (hetero) cyclic ring; or Y and R³ or R⁴ together form a 5, 6, or 7-membered heterocyclic ring with one of the alkyl groups of

NR³R⁴ ; Y is Cι~C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl, or C₃ -C₇ cycloalkyl, Cι-C₆ alkylamino (Ci-Cg) alkyl, or Cι-C₆ alkoxy (Ci-

C₆) alkyl; or

N- (Ci-Cg) alkyl piperazinyl, or piperidinyl.

18. A compound according to claim 1, which has the formula:

•145-

wherein

ROY- where Y is Ci-C₆ alkylene and R² represents hydrogen, Ci-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or Ci-Cg alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; R⁷ is hydrogen, halogen, mono- or di (C_ι-C₆) alkylamino, Ci- Cg alkyl, or C₃-C₇ cycloalkyl; R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², - NR³R⁴ ; R¹², R¹² , and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl, -NR³R⁴;

-146* R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-Cg alkoxy or Cι-C_β alkyl, or C₃-C cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

R¹¹ and R¹², or R¹² and R¹³ together with the atoms to which they are attached form an aryl , heteroaryl , or (hetero) cyclic ring; or Y and R³ or R⁴ together form a 5, 6, or 7-membered heterocyclic ring with one of the alkyl groups of

NR³R⁴ ; Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C_β alkyl, or C₃-C₇ cycloalkyl; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, Cι-C₆ alkylamino (Ci-Cg) alkyl, or Cι-C₆ alkoxy (Ci- Cg) alkyl; or NR³R⁴ represents a 5, 6, or 7-membered heterocyclic ring, such as for example, imidazolyl, pyrrolidinyl, morpholinyl, N-unsubstituted or

N- (Ci-Cg) alkyl piperazinyl, or piperidinyl.

19. A compound according to claim 18, wherein R¹¹, R^11' , R¹², R^12' , and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Cι-C_e) alkylamino.

-147-

20. A compound according to claim 1, which has the formula :

R „ /^T=E

N ^ *N' H'^V

^R'-÷ " -N /=< R ^R1"1 V R.U'²

wherein

T is nitrogen or CR^11' , E is nitrogen or CR^12' , and D is nitrogen or CR¹³, provided that no more than one of T, E and D is nitrogen; A is methylene substituted with R⁵R⁶, where R⁵ and R⁶ independently represent hydrogen or Cι-C₆ alkyl; q is 0 or an integer of from 1-3; R represents

ROY- where Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C^ -C_η cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or Ci-Cg alkyl, Cι-C₅ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group;

R⁷ is hydrogen, halogen, mono- or di (Cι-C₆) alkylamino, Ci- C₆ alkyl, or C₃-C₇ cycloalkyl;

-148* R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², - NR³R⁴ ; R¹², R^12' , and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl , -NR³R⁴;

R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-Cg alkoxy or Cι-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

R¹¹ and R¹², or R¹² and R¹³ together with the atoms to which they are attached form an aryl, heteroaryl, or (hetero) cyclic ring; or Y and R³ or R⁴ together form a 5, 6, or 7-membered heterocyclic ring with one of the alkyl groups of

NR³R⁴ ; Y is Ci-Cg alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, Cι-C₆ alkylamino (Ci-Cg) alkyl, or Cι-C₆ alkoxy (Ci-

C₆) alkyl; or

N- (Ci-Cg) alkyl piperazinyl, or piperidinyl. -149-

21. A compound according to claim 20, wherein q is 0 or A is methylene or ethylene.

22. A compound according to claim 21, wherein R¹¹, R^11' , R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι~C₆ alkoxy, or mono- or di (Cι-C₆) alkylamino.

23. A compound according to claim 22, wherein R^11' and R^12' are hydrogen and R¹¹, R¹², and R¹³ independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkoxy, or Cι-C₆ alkyl.

24. A compound according to claim 22, wherein R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Ci- Cβ) alkylamino; and R¹², R^12', and R¹³ are the same or different and represent halogen, Cι-C₆ alkyl, R²OY-, where Y is a bond or Ci- C₆ alkylene and R² is optionally substituted with -

NR³R⁴.

25. A compound according to claim 22, wherein one of R¹², R^12', and R¹³ is R²OY- , Y is a bond, methylene, or ethylene, and R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group.

-150-

26. A compound according to claim 22, wherein one of R¹², R^12', and R¹³ is R²OY-, Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or Cι-C₆ alkyl.

27. A compound according to claim 1, which has the formula:

R¹² R13

\ R

R R O

~& «

wherein

R represents

R²OY- where Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or Ci-Cg alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; R⁷ is hydrogen, halogen, mono- or di (Ci-Cg) alkylamino, Ci-

C₆ alkyl, or C₃-C₇ cycloalkyl;

•151- R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², - NR³R⁴ ; R¹², R^12', and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl , -NR³R⁴;

R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-C alkoxy or Cι-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

(hetero) cyclic ring; or

NR³R⁴ ;

Y is Ci-Cg alkylene and R² represents hydrogen, Cι-C₆ alkyl , or C₃-C₇ cycloalkyl ; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl , or C₃-C₇ cycloalkyl , Cι-C₆ alkylamino (Cι-C₆) alkyl , or Cι-C₆ alkoxy (Ci-

C₆) alkyl ; or

N- (Ci-Cg) alkyl piperazinyl, or piperidinyl. -152-

28. A compound according to claim 27, where R¹¹, R^11' , R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Ci-C₆ alkoxy, or mono- or di (Ci-C₆) alkylamino.

29. A compound according to claim 27, wherein any three of R¹¹, R^11', R¹², R^12', and R¹³ are hydrogen.

30. A compound according to claim 27, wherein R^11' , R¹², and R^12' are hydrogen and R¹¹ and R¹³ independently represent hydrogen, halogen, hydroxy, or Cι-C₆ alkoxy.

31. A compound according to claim 27, wherein R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Ci- C₆) alkylamino; and

R¹², R^12', and R¹³ are the same or different and represent halogen, Cι-C₆ alkyl, R²0Y- , where Y is a bond or Ci-C₆ alkylene and R² is optionally substituted with -NR³R⁴.

32. A compound according to claim 31, wherein only one of R¹², R^12', and R¹³ is R²0Y- and Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group.

-153-

33. A compound according to claim 31, wherein only one of R¹², R^12', and R¹³ is R²OY- and Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or Cι-C₆ alkyl.

34. A compound according to claim 27, wherein

R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Ci-Cβ alkyl, Cι-C₆ alkoxy, or mono- or di (Ci- C₆) alkylamino; and

35. A compound according to claim 34, wherein the -NR³R⁴ groups substituted on the R¹², R^12', and R¹³ groups are morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl, provided that not more than one of R¹², R^12' , and R¹³ carries - NR³R .

36. A compound according to claim 1, which has the formula :

^■154* O 99/40092

wherein

A is methylene substituted with R^SR⁶, where R⁵ and R⁶ independently represent hydrogen or Cι-C₆ alkyl; q is 0 or an integer of from 1-3; R represents

R²OY- where Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or Ci-Cg alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; R⁷ is hydrogen, halogen, mono- or di (Cι-C₆) alkylamino, Ci-

C₆ alkyl, or C₃-C₇ cycloalkyl; R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², - NR³R⁴ ;

R , R , and R .13 are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl , -NR 3*R->4 ;

^■155* ROY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-Cg alkoxy or Cι-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

(hetero) cyclic ring; or

NR³R⁴ ;

Y is Cι-C₆ alkylene and R² represents hydrogen, Cχ-Cg alkyl , or C₃ -C₇ cycloalkyl ; and R³ and R⁴ are the same or different and represent hydrogen, Cι-C₆ alkyl , or C₃-C₇ cycloalkyl , Cι-C₆ alkylamino (Ci-Cg) alkyl , or Cι-C₆ alkoxy (Ci-

C₆) alkyl ; or

N- (Cι-C₆) alkyl piperazinyl, or piperidinyl.

37. A compound according to claim 36, where R¹¹, R^11' , R¹², R^12', and R¹³ are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Ci-Cg) alkylamino.

-156-

38. A compound according to claim 36, wherein any three of R¹¹, R^11', R¹², R^12', and R¹³ are hydrogen.

39. A compound according to claim 36, wherein R^11' , R¹², and R^12' are hydrogen and R¹¹ and R¹³ independently represent hydrogen, halogen, hydroxy, or C_ι-C₆ alkoxy.

40. A compound according to claim 36, wherein R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (C_x- C₆) alkylamino; and

R¹², R^12', and R¹³ are the same or different and represent halogen, Cι-C₆ alkyl, R²0Y-, where Y is a bond or Cι-C₃ alkylene and R² is optionally substituted with -NR³R⁴.

41. A compound according to claim 40, wherein only one of R¹², R^12', and R¹³ is R²OY- and Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group.

42. A compound according to claim 40, wherein only one of R¹², R^12', and R¹³ is R²OY- and Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or Cι-C₆ alkyl .

-157-

43. A compound according to claim 36, wherein

R¹¹ and R^11' independently represent hydrogen, halogen, hydroxy, Cι-C₆ alkyl, Cι-C₆ alkoxy, or mono- or di (Ci-

C₆) alkylamino; and

R¹², R^12', and R¹³ are the same or different and represent hydrogen, halogen, or Cι-C₆ alkyl substituted on its alkyl portion with -NR³R⁴, provided that at least one of R¹², R^12' , and

R¹³ is substituted Cι-C₆ alkyl.

44. A compound according to claim 43, wherein the -NR 3-Rn4

groups substituted on the R ,12' and R •13 groups are morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl, provided that not more than one of R¹², R^12' , and R¹³ carries -

NR³R⁴ ,

45. A compound according to claim 1, which has the formula :

J=E

wherein

T is nitrogen or CR^11' , E is nitrogen or CR^12' , and D is nitrogen or CR¹³, provided that no more than one of T, E and D is nitrogen;

-158- A is methylene substituted with R^SR⁶, where R⁵ and R⁶ independently represent hydrogen or Cι-C₆ alkyl; q is 0 or an integer of from 1-3; R represents R²OY- where Y is Cι-C₆ alkylene and R² represents hydrogen, Cι-C₆ alkyl, or C₃-C₇ cycloalkyl, and Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; or Ci-C alkyl, Cι-C₆ alkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴, or a heterocyclic group; R⁷ is hydrogen, halogen, mono- or di (Cι-C₆) alkylamino, Ci- C₆ alkyl, or C₃-C₇ cycloalkyl; R¹¹ and R^11' are the same or different and are selected from hydrogen, halogen, hydroxy, Cι-C₆ alkyl, -OR², - NR³R⁴ ; R¹², R^12' , and R¹³ are the same or different and represent hydrogen, halogen, hydroxy, trifluoromethyl, -NR³R⁴; R²OY- wherein Y and R², when R² is not hydrogen, are independently optionally substituted with -NR³R⁴; Ci-Cg alkoxy or Cι-C₆ alkyl, or C₃-C₇ cycloalkoxy, each of which is optionally substituted on its alkyl portion with -NR³R⁴; or

^■159- R¹¹ and R¹², or R¹² and R¹³ together with the atoms to which they are attached form an aryl, heteroaryl, or

(hetero) cyclic ring; or

NR³R⁴ ;

Y is Ci-Cg alkylene and R² represents hydrogen, Cι-C₆ alkyl , or C^-C-x cycloalkyl ; and R³ and R⁴ are the same or different and represent hydrogen, Ci-C alkyl , or C₃ -C₇ cycloalkyl , C_ι-C₆ alkylamino (Ci-Cg ) alkyl , or Ci-Cg alkoxy (Ci-

C₆) alkyl ; or

N- (C_ι-C₆) alkyl piperazinyl, or piperidinyl.

46. A compound according to claim 45, wherein only one of T, E, and D is nitrogen.

47. A compound according to claim 20, wherein only one of T, E, and D is nitrogen.

48. A compound according to claim 46, wherein R^11' and R^12' are hydrogen; and

-160- R¹¹, R¹², and R¹³ are the same or different and represent halogen, Cι-C₆ alkyl, R²OY- , where Y is a bond or Ci- C₆ alkylene and R² is substituted with -NR³R⁴.

49. A compound according to claim 48, wherein only one of R¹¹, R¹², and R¹³ is R²OY- , and Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where NR³R⁴ forms a morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl group.

50. A compound according to claim 48, wherein only one of R¹¹, R¹², and R¹³ is R²OY- , and Y is a bond, methylene, or ethylene, R² is methyl or ethyl substituted with NR³R⁴ where R³ and R⁴ independently represent hydrogen or Cι-C₆ alkyl.

51. A compound according to claim 50, wherein the NR³R⁴ group on the R¹², R^12' , and R¹³ groups are morpholinyl, piperidinyl, piperazinyl, or pyrrolidinyl, provided that not more than one of R¹², R^12' , and R¹³ carries -NR³R⁴.

52. A compound according to claim 4, which is: N-Phenyl-7-oxo-5, 7, 8, 9-4H-dipyrido [l,2-a:3'2' - d] imidazole-6-carboxamide; or

N- (2 -Fluorophenyl) -7-oxo- 5 , 7, 8 , 9-4H-dipyrido [1, 2-a : 3 ' 2 ' - d] imidazole-6-carboxamide .

53. A compound according to claim 6, which is:

-161- N- (2-Fluorophenyl) -8-0x0-6, 7, 8 , 10-4H-dipyrido [1, 2- a: 3 ' , 4 ' -d] imidazole-9-carboxamide ;

N-Phenyl-8-oxo-6,7,8, 10-4H-dipyrido [1 , 2-a: 3 ' ,4' - d] imidazole-9-carboxamide; N- (3-Methoxyphenyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a: 3 ' , 4 ' -d] imidazole-9-carboxamide;

N- (4-Ethoxyphenyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a: 3 ' , 4 ' -d] imidazole-9-carboxamide;

N- (4-Fluorophenyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a: 3 ' , 4 ' -d] imidazole- 9-carboxamide;

N- (2 -Chlorophenyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1,2- a: 3 ' , 4 ' -d] imidazole-9-carboxamide;

N- (4-Methoxyphenyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1,2- a: 3 ' , 4 ' -d] imidazole-9-carboxamide; N- (2, 4 -Difluorophenyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1,2- a : 3 ' , 4 ' -d] imidazole-9-carboxamide ;

N- (2-Fluoro-4-methoxyphenyl) -8-0x0-6, 7, 8, 10-4H- dipyrido [1, 2-a: 3 ' ,4' -d] imidazole-9-carboxamide; or

N- (2-Methoxyphenyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a : 3 ' , 4 ' -d] imidazole-9-carboxamide .

54. A compound according to claim 6, which is: N- (2, 5-Difluorophenyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1,2- a: 3 ' , 4 ' -d] imidazole- 9-carboxamide; N- (2-Fluoro-4-methylphenyl) -8-0x0-6, 7 , 8 , 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide;

-162- N- (3 -Fluorophenyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1, 2- a:3' ,4' -d] imidazole-9-carboxamide;

N- (2-Fluoro-5-methylphenyl) -8-0x0-6, 7,8, 10-4H- dipyrido [1, 2 -a: 3 ' , 4 ' -d] imidazole-9-carboxamide; N- [2-Fluoro-5- (trifluoromethyl) phenyl] -8-0x0-6, 7, 8 , 10-4H- dipyrido [1, 2-a:3' ,4' -d] imidazole-9-carboxamide ;

N- [3,4- (Methylenedioxy) phenyl] -8-0x0-6, 7,8, 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide;

N- (2-Fluoro-4-bromophenyl) -8-0x0-6, 7,8, 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide ;

N- (2 -Fluoro-4 -chlorophenyl) -8-0x0-6, 7,8, 10-4H- dipyrido [1, 2-a : 3 ' ,4' -d] imidazole-9-carboxamide;

N- (2,3-Difluorophenyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1, 2- a:3 ' , 4' -d] imidazole-9-carboxamide; N- (2-Fluoro-5-methoxyphenyl) -8-0x0-6, 7,8, 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide; or

N- (2-Fluoro-4-ethoxyphenyl) -8-0x0-6, 7,8, 10-4H- dipyrido [1, 2 -a: 3 ' , 4 ' -d] imidazole-9-carboxamide .

55. A compound according to claim 5, which is

N-{2-Fluoro-4- [2- (piperidin-1-yl) ethoxy] phenyl } -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3' ,4' -d] imidazole- 9-carboxamide ;

N-{ [2-Fluoro-4- (morpholin-4 -ylethoxy) ] phenyl} -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3' ,4' -d] imidazole- 9-carboxamide ; N- { [2-Fluoro-4- (2- (ethylamino) ethoxy) ] phenyl} -8-oxo-

6,7,8, 10-4H-dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide;

-163- N-{ [2-Fluoro-4- (pyrrolidin-1-ylmethyl) ] phenyl} -8 -oxo- 6,7,8, 10-4H-dipyrido [1, 2-a :3 ' , 4 ' -d] imidazole-9-carboxamide;

N-{ [2-Fluoro-4- (morpholin-4-ylmethyl) ] phenyl } -8 -oxo- 6,7,8, 10 -4H-dipyrido [1 , 2 -a : 3 ' , 4 ' -d] imidazole-9-carboxamide ; N-{ [2-Fluoro-5- (N,N-dimethylaminomethyl) ] phenyl} -8-oxo- 6,7,8, 10-4H-dipyrido [1 , 2 -a : 3 ' , 4 ' -d] imidazole-9-carboxamide ;

N-{ [2-Fluoro-5- (pyrrolidin- 1-ylmethyl) ] phenyl} -8-oxo- 6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide; N-{2-Fluoro-5- [2- (piperazin-1-yl) methyl] phenyl } -8 -oxo- 6,7,8,10-4H-diρyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide tris (trifluoroacetate) ;

N-{ [2-Fluoro-5- (2- (dimethylamino) ethoxymethyl) ] phenyl} -8 oxo-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide; N-{2-Fluoro-5- [2- (piperidin-1-yl) ethoxy] phenyl} -8-oxo- 6,7,8, 10-4H-dipyrido [1, 2-a : 3 ' , 4 ' -d] imidazole- 9-carboxamide;

(R) -N- [4- (Pyrrolidin-2 -ylmethoxy) phenyl] -8-oxo-6, 7,8, 10- 4H-dipyrido [1, 2-a: 3 ' , 4 ' -d] imidazole-9-carboxamide;

(S) -N- [4- (Pyrrolidin-2 -ylmethoxy) phenyl] -8-oxo-6, 7,8, 10- 4H-dipyrido [l,2-a:3' ,4'-d] imidazole-9-carboxamide;

N- [4- (Piperid-3 -ylmethoxy) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido [1, 2-a: 3 ' ,4' -d] imidazole-9-carboxamide; or

N- [4- (2 -Piperid-2 -ylethoxy) phenyl] -8-oxo-6, 7 , 8 , 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide .

56. A compound according to claim 5, which is:

-164- N- [4- (2- (Ethylamino) ethoxy) phenyl] -8 -oxo-6, 7, 8 , 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole- 9-carboxamide ;

N- [4- (2- (Propylamino) ethoxy) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide; N- [4- (2- (Isopropyl) aminoethoxy) phenyl] -8 -oxo-6, 7,8, 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide;

N- [4- (2- (Butylamino) ethoxy) phenyl] -8 -oxo-6, 7, 8, 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide;

N- [4- (2- (tert-Butylamino) ethoxy) phenyl] -8-oxo-6, 7,8, 10- 4H-dipyrido [l,2-a:3' ,4' -d] imidazole- 9-carboxamide;

N- [3-Fluoro-4- (2- (propylamino) ethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide;

N- [2-Methyl-4- (2- (propylamino) ethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [1, 2-a: 3 ' ,4' -d] imidazole-9-carboxamide; N- (2 -Fluorophenyl) -8-oxo-10- (2- (methylamino) ethyl) -

6,7,8, 10-4H-dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide; N- [4- (3- (Ethylamino) propoxy) phenyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide;

N- [4- (3- (Butylamino) propoxy) phenyl] -8 -oxo-6, 7,8, 10-4H- dipyrido [l,2-a:3',4'-d] imidazole- 9-carboxamide;

N- [3- (2- (Propylamino) ethoxy) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide ;

N- [4- (2- (Cyclopropylamino) ethoxy) phenyl] -8-oxo-6, 7, 8, 10- 4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide ; N- [4- (2- (Isobutylamino) ethoxy) phenyl] -8 -oxo-6, 7, 8, 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole- 9-carboxamide;

-165- N- (2 -Fluorophenyl) -3- (2-hydroxyethoxy) -8-oxo-6, 7, 8 , 10-4H- dipyrido [l,2-a:3' ,4'-d] imidazole-9-carboxamide;

N- (2 -Fluorophenyl) -3- (2- (propylamino) ethoxy) -8-oxo - 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide .

57. A compound according to claim 11, which is N- (2-fluorobenzyl) -8-oxo-6, 7,8, 10-tetrahydro- dipyrido [1 , 2-a : 3 ' , 4 ' -d] imidazole-9-carboxamide;

N- (2-fluorobenzyl) -8 -oxo- 10-methyl-6 , 7,8, 10-tetrahydro- dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide ;

N-Benzyl-8-oxo-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' - d] imidazole- 9-carboxamide;

N- (4-Fluorobenzyl) -8-oxo-6, 7, 8, 10-4H-dipyrido [1, 2- a:3 ' , 4 ' -d] imidazole-9-carboxamide; N- (2-Fluorobenzyl) -8-oxo-6, 7,8, 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole-9-carboxamide ;

N- (3-Fluorobenzyl) -8 -oxo-6, 7,8, 10-4H-dipyrido [1, 2- a:3 ' , 4 ' -d] imidazole- 9-carboxamide;

N- (2-Ethoxybenzyl) -8-oxo-6, 7,8, 10-4H-dipyrido [1 , 2- a: 3 ' , 4 ' -d] imidazole-9-carboxamide;

N- (2-Chlorobenzyl) -8 -oxo-6, 7,8, 10-4H-dipyrido [1,2- a:3' ,4' -d] imidazole-9-carboxamide ;

N- (3-Chlorobenzyl) -8-oxo-6, 7, 8, 10-4H-dipyrido [1,2- a:3 ' ,4' -d] imidazole-9-carboxamide; N- (4-Ethoxybenzyl) -8-oxo-6, 7,8, 10-4H-dipyrido [1,2- a:3 ' ,4' -d] imidazole- 9-carboxamide ;

-166- N- (4-Methoxybenzyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a: 3 ' , 4 ' -d] imidazole-9-carboxamide;

N- (2-Methoxybenzyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a : 3 ' , 4 ' -d] imidazole-9-carboxamide; N- [2- (4-Methoxyphenyl) ethyl] -8-0x0-6, 7, 8 , 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide;

N- (4-Methylbenzyl) -8-0x0-6, 7, 8, 10-4H-dipyrido [1 , 2- a : 3 ' , 4 ' -d] imidazole-9-carboxamide;

N- (2, 4-Difluorobenzyl) -8-oxo-6,7,8, 10-4H-dipyrido [1 , 2- a:3 ' , 4 ' -d] imidazole-9-carboxamide; or

N- (2, 5-Difluorobenzyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1 , 2- a: 3 ' , 4 ' -d] imidazole-9-carboxamide .

58. A compound according to claim 11, which is N- [3- (Trifluoromethyl) benzyl] -8-oxo-6,7, 8, 10-4H- dipyrido [1, 2-a: 3 ' , 4 ' -d] imidazole- 9-carboxamide ;

N- (2, 6-Difluorobenzyl) -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a: 3 ' , 4 ' -d] imidazole-9-carboxamide ;

N- [4- (1-Imidazolylmethyl) benzyl] -8-0x0-6, 7,8, 10-4H- dipyrido [1, 2-a: 3 ' ,4' -d] imidazole- 9-carboxamide ;

N- (2-Fluorobenzyl) -8-oxo-10-methyl-6, 7,8, 10-4H- dipyrido [1 , 2-a : 3 ' , 4 ' -d] imidazole-9-carboxamide;

N- [2-Fluoro-4- (2- (dimethylamino) ethoxy) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide;

-167- N-{2-Fluoro-5- [ (4-methylpiperizin-l-yl) methyl] benzyl } -8- oxo-6,7, 8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide;

N- [2-Fluoro-4- (pyrrolidin- 1-ylmethyl) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide ;

N- [2-Fluoro-5- [ (pyrrolidin- 1-ylmethyl) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole- 9-carboxamide;

N- (2-Fluorobenzyl) -8-oxo-10- [2- (morpholin-4-yl) ethyl] - 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide; N- (2-Fluorobenzyl) -8-oxo-10- (2-methylaminoethyl) -

6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide;

N- [2-Fluoro-4- (3- (dimethylamino) propoxy) benzyl] -8-oxo-10- ethyl-6,7, 8 , 10-4H-dipyrido [1, 2 -a: 3 ' ,4' -d] imidazole- 9- carboxamide ; N- [2-Fluoro-4- (2 -morpholin-4 -ylethoxy) benzyl] -8-oxo-

6,7,8, 10-4H-dipyrido [1, 2-a : 3 ' , 4 ' -d] imidazole- 9 -carboxamide;

N- [2-Fluoro-4- (2-piperidin-l-ylethoxy) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido [1, 2-a: 3 ' , 4 ' -d] imidazole-9 -carboxamide;

N- [2-Fluoro-4- (3-piperidin-l-ylpropoxy) benzyl] -8-oxo- 6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide ;

N- [2-Fluoro-4- (2- (dimethylamino) ethoxy) benzyl] -8-oxo-10- ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide; or

N- [4- (3- (Dimethylamino) propoxy) benzyl] -8-oxo-6, 7,8, 10-4H- dipyrido [l,2-a:3',4'-d] imidazole- 9-carboxamide .

^•168*

59. A compound according to claim 11, which is

N- [4- (2- (Dimethylamino) ethoxy) benzyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide;

N- [4- (2-Pyrrolidin-l-ylethoxy) benzyl] -8-oxo-6, 7 , 8 , 10-4H- dipyrido [1, 2-a:3' ,4' -d] imidazole-9-carboxamide;

N- [4- (3 -Pyrrolidin-1-ylpropoxy) benzyl] -8-oxo-6, 7,8, 10-4H- dipyridσ [l,2-a:3' ,4'-d] imidazole- 9-carboxamide ;

N- [4- (4 -Pyrrolidin-1-ylbutoxy) benzyl] -8 -oxo-6, 7, 8, 10-4H- dipyrido [1, 2-a:3' ,4'-d] imidazole-9-carboxamide ; N- [2-Fluoro-4- (2 -piperidin-1-ylethoxy) benzyl] -8-oxo-10- ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' , 4 ' -d] imidazole-9- carboxamide;

N- [2-Fluoro-4- (2-morpholin-4-ylethoxy) benzyl] -8-oxo-10- ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' , 4 ' -d] imidazole-9- carboxamide;

N- [4- (2- (dimethylamino) ethoxy) benzyl] -8 -oxo- 10-ethyl - 6,7, 8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide;

N- [4- (4 -Pyrrolidin-1-ylbutoxy) benzyl] -8-oxo-10-ethyl- 6,7,8, 10-4H-dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide; N- [2-Fluoro-4- (3 -pyrrolidin- 1-ylpropoxy) benzyl] -8-oxo- 6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide;

N- [3- (2 -Morpholin-4 -ylethoxy) benzyl] -8-oxo-6, 7,8, 10-4H- dipyrido[l,2-a:3' ,4' -d] imidazole- 9-carboxamide ;

N- [3- (3 -Piperidin-1-ylpropoxy) benzyl] -8-oxo-6, 7, 8 , 10-4H- dipyrido [l,2-a:3' ,4' -d] imidazole-9-carboxamide;

-169- N- [4- (2 -Morpholin-4 -ylethoxy) benzyl] -8-oxo-6, 7,8, 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide ;

N- [4- (2- (1-Methylpyrrolidin-2 -yl) ethoxy) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3 ' ,4'-d] imidazole-9-carboxamide; N- [3- (2-Piperidin-l-ylethoxy) benzyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [l,2-a:3' ,4'-d] imidazole-9-carboxamide;

N- [4- (2 -Piperidin-1-ylethoxy) benzyl] -8-oxo-6, 7,8, 10-4H- dipyrido [1, 2 -a: 3' ,4' -d] imidazole- 9-carboxamide; or

N- [4- (3 -Piperidin-1-ylethoxy) benzyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [1, 2 -a: 3 ' ,4' -d] imidazole-9-carboxamide;

60. A compound according to claim 11, which is

N- [2-Fluoro-4- (2-pyrrolidin-1-ylethoxy) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide ; N- [4- (2- (Diethylamino) ethoxy) benzyl] -8 -oxo-6, 7,8, 10-4H- dipyrido [1, 2-a: 3 ' ,4' -d] imidazole- 9-carboxamide;

N- [3- (2- (Diethylamino) ethoxy) benzyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide;

N- [2-Fluoro-4- (3 -Piperidin-1-ylpropoxy) benzyl] -8-oxo-10- (2-methoxyethoxy) -6,7,8, 10-4H-dipyrido [l,2-a:3',4'- d] imidazole- 9-carboxamide ;

N- [2-Fluoro-4- (2- (Dimethylamino) ethoxy) benzyl] -8-oxo-10- propyl-6,7, 8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole- 9- carboxamide;

■170- N- [2-Fluoro-4- (3- (Dimethylamino) propoxy) benzyl] -8-oxo-lO- propyl-6, 7, 8, 10-4H-dipyrido [1, 2-a:3' ,4' -d] imidazole-9- carboxamide;

N- [2-Fluoro-4- (2- (Dimethylamino) ethoxy) benzyl] -8-oxo-10- butyl-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide;

N- [2-Fluoro-4- (3- (Dimethylamino) propoxy) benzyl] -8-oxo-10- butyl-6 , 7,8, 10-4H-dipyrido [1 , 2 -a : 3 ' , 4 ' -d] imidazole-9- carboxamide ; N- [2-Fluoro-4- (3 -Piperidin-1-ylpropoxy) benzyl] -8-oxo-10- ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide ;

N- [2-Fluoro-4- (2-Pyrrolidin-l-ylethoxy) benzyl] -8-oxo-10- ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide;

N- [2-Fluoro-4- (3-Pyrrolidin-l-ylpropoxy) benzyl] -8-oxo-10- ethyl-6,7,8,10-4H-dipyrido[l,2-a:3' , 4 ' -d] imidazole-9- carboxamide ;

N- [3- (2-Piperidin-l-ylethoxy) benzyl] -8 -oxo-10-ethyl - 6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide ;

N- [2-Fluoro-4- (2-Pyrrolidin-l-ylethoxy) benzyl] -8-oxo-10- propyl-6,7,8, 10-4H-dipyrido [1, 2-a: 3 ' ,4' -d] imidazole-9- carboxamide ;

N- [2-Fluoro-4- (3 -Pyrrolidin-1-ylpropoxy) benzyl] -8-oxo-10* propyl-6,7,8,10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9- carboxamide;

-171- N- [4- (2 -Piperidin-1-ylethoxy) benzyl] -8-oxo-10-ethyl- 6,7,8, 10-4H-dipyrido[l,2-a:3' ,4' -d] imidazole-9-carboxamide ;

N- [4- (2- (Diethylamino) ethoxy) benzyl] -8-oxo-10-ethyl- 6,7,8, 10-4H-dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide ; N- [4- (3-Piperidin-l-ylpropoxy) benzyl] -8 -oxo-10 -ethyl-

6,7,8, 10-4H-dipyrido [l,2-a:3 ' ,4' -d] imidazole-9-carboxamide; or

N- (2-Fluorobenzyl) -3- (2 -hydroxyethoxy) -8-oxo-6, 7, 8, 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide.

61. A compound according to claim 11, which is N- [2- (2 -Fluorophenyl) ethyl] -8-oxo-6, 7, 8 , 10-4H- dipyrido [1, 2-a: 3 ' ,4' -d] imidazole-9-carboxamide;

N- [1- (4-Fluorophenyl) ethyl] -8-oxo-6, 7, 8 , 10-4H- dipyrido [l,2-a:3',4'-d] imidazole-9-carboxamide ; N- [1- (4-Bromophenyl)ethyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [1 , 2-a: 3 ' ,4' -d] imidazole-9-carboxamide;

N- [1- (Phenyl) ethyl] -8 -oxo-6, 7, 8 , 10-4H-dipyrido [1,2- a : 3 ' , 4 ' -d] imidazole-9-carboxamide ;

(R) - (+) -N- [1- (Phenyl) ethyl] -8-oxo-6, 7, 8 , 10-4H- dipyrido [1 , 2-a : 3 ' ,4' -d] imidazole-9-carboxamide;

(S) - (-) -N- [1- (4-Bromophenyl) ethyl] -8-oxo-6, 7, 8 , 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole- 9-carboxamide ;

(S) - (-) -N- [1- (Phenyl) ethyl] -8-oxo-6, 7 , 8 , 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide; N- [ ( 1 -Methyl -1-Phenyl) ethyl] -8-oxo-6, 7, 8 , 10-4H- dipyrido [1, 2 -a: 3 ' , 4 ' -d] imidazole-9-carboxamide;

-172- N- [1- (Phenyl) propyl] -8-0x0-6, 7,8, 10-4H-dipyrido [1,2- a: 3 ' , 4 ' -d] imidazole- 9-carboxamide;

(R) -N- [1- (1-Naphthyl) ethyl] -8-0x0-6, 7, 8, 10-4H- dipyrido [1,2 -a: 3 ' ,4' -d] imidazole-9-carboxamide; N- [1,2, 3, 4-Tetrahydro-1-naphthyl] -8-0x0-6, 7, 8,10-4H- dipyrido [1, 2 -a: 3 ' ,4' -d] imidazole-9-carboxamide ;

N- [1-Naphthylmethyl] -8-0x0-6, 7, 8, 10-4H-dipyrido [1, 2- a:3' , 4' -d] imidazole-9-carboxamide;

(S) -N- [1- (1-Naphthyl) ethyl] -8-0x0-6, 7, 8, 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide ;

N- (1-Naphthyl) -8-0x0-6, 7, 8 , 10-4H-dipyrido [1, 2-a: 3 ' ,4' - d] imidazole- 9-carboxamide; or

N- (2 -Naphthyl) -8-0x0-6, 7, 8 , 10-4H-dipyrido [1, 2 -a: 3 ' ,4' - d] imidazole-9-carboxamide.

62. A compound according to claim 17, which is N-Cyclohexyl-8-oxo-6,7,8, 10-4H-dipyrido [1, 2-a: 3 ' ,4' - d] imidazole-9-carboxamide; or

N- (Cyclohexylmethyl) -8-0x0-6, 7, 8 , 10-4H-dipyrido [1,2- a : 3 ' , 4 ' -d] imidazole-9-carboxamide .

63. A compound according to claim 18, which is

N- (2-fluorobenzyl) -2 -methyl-8 -oxo- 1, 2 , 3 , 4 , 6, 7, 8, 10-8H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide; N- (2 -Fluorophenyl) -2 -methyl -8 -oxo- 1, 2 , 3 , 4 , 6 , 7, 8 , 10-8H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole- 9-carboxamide; or

-173- N- (2-Fluorobenzyl) -2 -methyl-8 -oxo-1 , 2 , 3 , 4 , 6,7,8, 10-8H- dipyrido [1, 2-a: 3 ' ,4' -d] imidazole-9-carboxamide .

64. A compound according to claim 20, which is N- (4-Pyridylmethyl) -8-oxo-6, 7, 8, 10-4H-dipyrido [1, 2- a : 3 ' , 4 ' -d] imidazole-9-carboxamide;

N- (3-Pyridylmethyl) -8-oxo-6, 7,8, 10-4H-dipyrido [1,2- a:3 ' , 4 ' -d] imidazole-9-carboxamide;

N- (2-Pyridylmethyl) -8-oxo-6, 7, 8, 10-4H-dipyrido [1,2- a : 3 ' , 4 ' -d] imidazole-9-carboxamide;

N- (5-Methoxy-3-pyridyl) -8-oxo-6, 7, 8 , 10-4H-dipyrido [1,2- a:3 ' ,4' -d] imidazole-9-carboxamide ;

N- [2- (2- (Ethylamino) ethoxy) pyrid-5-yl] -8-oxo-6, 7,8, 10-4H- dipyrido [1, 2-a:3 ' ,4' -d] imidazole-9-carboxamide ; N- [2- (2- (Butylamino) ethoxy) pyrid-5-yl] -8 -oxo-6, 7, 8 , 10-4H- dipyrido [1, 2-a: 3 ' ,4'-d] imidazole-9-carboxamide; or

N- (2-Ethoxypyrid-5-yl) -8 -oxo-6, 7,8, 10-4H-dipyrido [1,2- a:3 ' , 4 ' -d] imidazole-9-carboxamide.

65. A compound according to claim 1, which is

N- (1-Indanyl) -8 -oxo-6, 7, 8 , 10-4H-dipyrido [1, 2-a: 3 ' ,4' - d] imidazole-9-carboxamide;

N- (2-fluorobenzyl) -2 -methyl-8 -oxo-6, 7,8, 10-tetrahydro- dipyrido [1, 2-a: 3 ', 4 ' -d] imidazole-9-carboxamide iodide; or N- (3-Ethoxypropyl) -8-oxo-6, 7,8, 10-4H-dipyrido [1,2- a:3 ' , 4' -d] imidazole- 9-carboxamide.

-174-

66. A compound according to claim 27, which is N- (2 -Fluorophenyl) -8-oxo-6, 7, 8, 10-4H-dipyrido [1,2- a:2' , 3 ' -d] imidazole-9-carboxamide ; N- (2,4-Difluorophenyl) -8-oxo-6,7, 8, 10-4H-dipyrido [1, 2- a:2 ' , 3 ' -d] imidazole-9-carboxamide;

N- (4-Chloro-2-fluorophenyl) -8-oxo-6, 7, 8, 10-4H- dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide ;

N- (2 -Fluorophenyl) -8-oxo-10-methyl-6, 7,8, 10-4H- dipyrido [1, 2-a :2 ' ,3' -d] imidazole-9-carboxamide ;

N- [3- ( (Dimethylamino) methyl) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide;

N- [2-Fluoro-5- (morpholin-4-ylmethyl) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [1,2 -a: 2' ,3' -d] imidazole- 9-carboxamide ; N- [2-Fluoro-5- (pyrrolidin-1-ylmethyl) phenyl] -8-oxo-

6,7,8, 10-4H-dipyrido [l,2-a:2' ,3' -d] imidazole-9-carboxamide;

N- {2-Fluoro-5- [1- (4-methylpiperazin-l-yl) methyl] phenyl } - 8-oxo-6,7, 8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide ; N- [2-Fluoro-5- ( (dimethylamino) methyl) phenyl] -8-oxo-

6,7,8, 10-4H-dipyrido [l,2-a:2' ,3'-d] imidazole-9-carboxamide ;

N- [2-Fluoro-4- (morpholin-4 -ylethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:2' ,3' -d] imidazole-9-carboxamide ; N- [2-Fluoro-4- (morpholin-4-ylmethyl) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide;

^■175- N-{2-Fluoro-4- [2- (piperidin-1-yl) ethoxy] phenyl} -8-oxo- 6,7,8, 10-4H-dipyrido [1, 2 -a: 2 ' , 3 ' -d] imidazole-9-carboxamide; or

N- (2-Fluoro-5-{ [2- (piperidin-1-yl) ethoxy] methyl}phenyl) - 8-oxo-6,7, 8, 10-4H-dipyrido [1, 2 -a: 2 ' , 3 ' -d] imidazole-9- carboxamide .

67. A compound according to claim 27, which is

N- (2-Fluoro-5- { [2- (dimethylamino) ethoxy] methyl }phenyl) -8- oxo-6,7,8, 10-4H-dipyrido[l,2-a:2' , 3' -d] imidazole-9- carboxamide;

N- [2-Fluoro-4- (pyrrolidin-1-ylmethyl) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide;

N- [2-Fluoro-5- (piperazin-1-ylmethyl) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide; N-{2-Fluoro-5- [2- (morpholin-4-ylethoxy) methyl] phenyl } -8- oxo-6, 7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole- 9- carboxamide ;

N- {2-Fluoro-5- [bis (2 -methoxyethyl) amino] methylphenyl } -8- oxo-6,7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide;

N- [3- (2 -morpholin-4 -ylethoxy) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido [l,2-a:2' ,3' -d] imidazole-9-carboxamide;

N- [4- (2- (Propylamino) ethoxy) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido [1, 2-a:2 ' , 3 ' -d] imidazole- 9-carboxamide;

•176* N- {2-Fluoro-5- [2- (piperazin-1-ylethoxy) methyl] phenyl} -8- oxo-6,7, 8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide ;

N- [2-Fluoro-4- (2- (ethylamino) ethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide;

N- [4- (2- (Isopropylamino) ethoxy) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido [1, 2 -a: 2 ' , 3 ' -d] imidazole- 9-carboxamide;

N- [4- (2- (Ethylamino) ethoxy) phenyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [1, 2-a:2' ,3' -d] imidazole-9-carboxamide; N- [3-Fluoro-4- (2- (propylamino) ethoxy) phenyl] -8-oxo-

6,7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide; or

N- [4- (3- (Propylamino) propoxy) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido [1, 2-a:2' ,3' -d] imidazole-9-carboxamide .

68. A compound according to claim 27, which is

(eeeeee)N- [4- (3- (Butylamino) propoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide;

N- [4- (2- (Butylamino) ethoxy) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido [1, 2-a:2' ,3' -d] imidazole-9-carboxamide; N- [3- (2- (Propylamino) ethoxy) phenyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [1, 2-a:2' ,3' -d] imidazole-9-carboxamide;

N- [4- (2- (Cyclopropylamino) ethoxy) phenyl] -8-oxo-6 , 7,8,10- 4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide ;

N- (2 -Fluorophenyl) -8-oxo-10- (2-dimethylaminoethyl) - 6,7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide ;

-177- N- (2 -Fluorophenyl) -8-oxo-10- (2- (ethylamino) ethyl) - 6,7,8, 10-4H-dipyrido [1, 2-a:2' ,3' -d] imidazole-9-carboxamide;

N- [2-Fluoro-4- (2- (Propylamino) ethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido[l,2-a:2' , 3 ' -d] imidazole-9-carboxamide; N- [3- (2- (Butylamino) ethoxy) phenyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide ;

(R) -N- [4- (Pyrrolidin-2 -ylmethoxy) phenyl] -8-oxo-6, 7,8, 10- 4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide;

(S) -N- [4- (Pyrrolidin-2 -ylmethoxy) phenyl] -8-oxo-6, 7, 8, 10- 4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide ;

N- [4- (2- (t-Butylamino) ethoxy) phenyl] -8-oxo-6, 7,8, 10-4H- dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide ;

N- [4- (2- (Propylamino) ethoxy) phenyl] -8-oxo-10 -methyl - 6,7,8, 10-4H-dipyrido [l,2-a:2' ,3'-d] imidazole-9-carboxamide; N- [4- (2- (Isobutylamino) ethoxy) phenyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [1, 2-a:2 ' ,3' -d] imidazole-9-carboxamide;

N- [4- (2- (Cyclopropylmethylamino) ethoxy) phenyl] -8-oxo- 6,7,8, 10-4H-dipyrido [1, 2-a:2' ,3' -d] imidazole-9-carboxamide; or N- [4- (2- (Cyclopropylamino) ethoxy) phenyl] -8-oxo-6, 7, 8, 10- 4H-dipyrido [l,2-a:2' ,3' -d] imidazole- 9-carboxamide .

69. A compound according to claim 36, which is N- (2-Fluorobenzyl) -8-oxo-6, 7 , 8 , 10-4H-dipyrido [1,2- a:2 ' , 3 ' -d] imidazole-9-carboxamide ; N- (2-Fluorobenzyl) -8-oxo-10-methyl-6 , 7 , 8, 10-4H- dipyrido [1 , 2-a : 2 ' ,3' -d] imidazole- 9-carboxamide ;

-178- N- (2-Fluorobenzyl) -8-oxo-10- (2- (dimethylamino) ethyl) - 6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide;

N- [2- (2- (Dimethylamino) ethoxy) benzyl] -8-oxo-6, 7, 8, 10-4H- dipyrido [1, 2-a:2 ' , 3 ' -d] imidazole-9-carboxamide; N- [2-Fluoro-5- (piperidin- 1-ylmethyl) benzyl] -8-oxo-

6,7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide;

N- [2-Fluoro-5- (morpholin-4-ylmethyl) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole- 9-carboxamide;

N- (2-Fluorobenzyl) -8-oxo-10-cyclopropylmethyl-6 , 7,8,10- 4H-dipyrido [1, 2-a:2 ' , 3 ' -d] imidazole-9-carboxamide;

N- (2-Fluorobenzyl) -8-oxo-10- (2 -methoxyethyl) -6,7,8, 10-4H- dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide;

N- (2-Fluorobenzyl) -8-oxo-10-ethyl-6, 7, 8 , 10-4H- dipyrido [1, 2-a:2 ' , 3 ' -d] imidazole-9-carboxamide ; N- [2-Fluoro-4- (2- (dimethylamino) ethoxy) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:2' ,3'-d] imidazole-9-carboxamide;

N- [2-Fluoro-4- (3- (dimethylamino) propoxy) benzyl] -8-oxo- 6,7,8, 10-4H-dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide;

N- (2-Fluorobenzyl) -8-oxo-10- (3- (dimethylamino) propyl) - 6,7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide;

N- [2-Fluoro-4- (2- (dimethylamino) ethoxy) benzyl] -8-oxo-10- methyl-6,7, 8, 10-4H-dipyrido [1, 2-a :2 ' , 3 ' -d] imidazole-9- carboxamide;

N- [2-Fluoro-4- (2 -hydroxyethoxy) benzyl] -8 -oxo-10-methyl- 6,7,8, 10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole- 9-carboxamide ;

-179- N- [2-Fluoro-4- (2- (propylamino) ethoxy) benzyl] -8-oxo-lO- methyl -6,7,8, 10-4H-dipyrido [1 , 2 -a : 2 ' , 3 ' -d] imidazole-9- carboxamide;

N- {2 -Fluoro-4- [2 - (morpholin-4 -yl) ethoxy] benzyl } -8 -oxo-10- ethyl-6,7,8,10-4H-dipyrido[l,2-a:2' , 3 ' -d] imidazole-9- carboxamide ; or

N-{4- [2- (Morpholin-4-yl) ethoxy] benzyl} -8-oxo-10-ethyl- 6,7,8, 10-4H-dipyrido [1 , 2 -a : 2 ' , 3 ' -d] imidazole-9-carboxamide .

70. A compound according to claim 36, which is

N- { 3 - [2 - (Piperidin-1-yl) ethoxy] benzyl } -8-oxo-10 -ethyl - 6,7,8, 10-4H-dipyrido[l,2-a:2' , 3 ' -d] imidazole-9-carboxamide ;

N- [4- (2- (Propylamino) ethoxy) benzyl] -8-oxo-10-ethyl - 6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide ; N- [4- (2- (Isobutylamino) ethoxy) benzyl] -8-oxo-10-ethyl- 6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9-carboxamide

N- [2-Fluoro-4- (2- (propylamino) ethoxy) benzyl] -8-oxo-10- propyl-6,7,8, 10-4H-dipyrido [1 , 2 -a: 2 ' ,3'-d] imidazole- 9- carboxamide ; N- [2-Fluoro-4- (2- (Isobutylamino) ethoxy) benzyl] -8-oxo-10- propyl-6,7,8,10-4H-dipyrido[l,2-a:2' , 3 ' -d] imidazole-9- carboxamide;

N- [2-Fluoro-4- (3 -piperidin-1-ylpropoxy) benzyl] -8-oxo-10- ethyl-6,7,8, 10-4H-dipyrido [1 , 2 -a : 2 ' , 3 ' -d] imidazole- 9- carboxamide;

^•180- N- [2-Fluoro-4- (2- (propylamino) ethoxy) benzyl] -8-oxo-10- ethyl-6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide;

N- [2-Fluoro-4- (2- (isopropylamino) ethoxy) benzyl] -8-oxo-10- ethyl-6, 7, 8, 10-4H-dipyrido [l,2-a:2' ,3' -d] imidazole-9- carboxamide;

N- [2-Fluoro-4- (2- (isoamylamino) ethoxy) benzyl] -8-oxo-10- ethyl-6, 7,8, 10-4H-dipyrido [1 , 2 -a: 2 ' ,3' -d] imidazole-9- carboxamide; N- [4- (2- ( Isobutylamino) ethoxy) benzyl] -8 -oxo-10-ethyl- 6,7,8, 10-4H-dipyrido [1, 2 -a: 2 ' , 3 ' -d] imidazole-9-carboxamide;

N- [2-Fluoro- (2- (propylamino) ethoxy) benzyl] -8-oxo-10- propyl-6,7,8, 10-4H-dipyrido [1, 2 -a: 2 ' ,3' -d] imidazole-9- carboxamide ; N- [2-Fluoro-4- (2- (isobutylamino) ethoxy) benzyl] -8-oxo-10- propyl-6, 7,8, 10-4H-dipyrido [1, 2 -a: 2 ' ,3' -d] imidazole-9- carboxamide ;

N- [2-Fluoro-4- (3 -piperidinopropyl) benzyl] -8-oxo-10-ethyl- 6,7,8, 10-4H-dipyrido[l,2-a:2' , 3' -d] imidazole-9-carboxamide; N- [2-Fluoro-4- (2- (propylamino) ethoxy) benzyl] -8-oxo-10- ethyl-6, 7, 8, 10-4H-dipyrido [1, 2-a:2' , 3 ' -d] imidazole-9- carboxamide ;

N- [2-Fluoro-4- (2- (isopropylamino) ethoxy) benzyl] -8-oxo-10- ethyl-6,7, 8, 10-4H-dipyrido [1, 2 -a: 2 ' ,3' -d] imidazole-9- carboxamide;

^•181- N- [2-Fluoro-4- (2- (isobutylamino) ethoxy) benzyl] -8-oxo-10- ethyl-6,7,8,10-4H-dipyrido[l,2-a:2' ,3' -d] imidazole-9- carboxamide; or

(S) -N- (1-Naphth-l-ylethyl) -8-oxo-6, 7, 8 , 10-4H- dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide.

71. A compound according to claim 45, which is

N- [2- (2- (Ethylamino) ethoxy) -5-pyridyl] -8-oxo-6, 7,8, 10-4H- dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide; or N- [2- (2- (Butylamino) ethoxy) -5-pyridyl] -8-oxo-6 , 7, 8 , 10-4H- dipyrido [l,2-a:2',3'-d] imidazole-9-carboxamide .

•182*