# Patent

## Title
Compounds and compositions for the treatment of parasitic diseases

## Abstract

The invention provides a class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of priority to U.S. application Ser. No. 12/833,909, filed 9 Jul. 2010, which claims the benefit of U.S. Provisional Patent Application No. 61/224,433, filed 9 Jul. 2009. The full disclosures of these applications are incorporated herein by reference in their entirety and for all purposes.


BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention provides a class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria.
2. Background
Malaria is an infectious disease caused by four protozoan parasites: Plasmodium falciparum; Plasmodium vivax; Plasmodium ovale; and Plasmodium malaria. These four parasites are typically transmitted by the bite of an infected female Anopheles mosquito. Malaria is a problem in many parts of the world and over the last few decades the malaria burden has steadily increased. An estimated 1-3 million people die every year from malaria—mostly children under the age of 5. This increase in malaria mortality is due in part to the fact that Plasmodium falciparum, the deadliest malaria parasite, has acquired resistance against nearly all available antimalarial drugs, with the exception of the artemisinin derivatives.
Leishmaniasis is caused by one or more than 20 varieties of parasitic protozoa that belong to the genus Leishmania, and is transmitted by the bite of female sand flies. Leishmaniasis is endemic in about 88 countries, including many tropical and sub-tropical areas.
There are four main forms of Leishmaniasis. Visceral leishmaniasis, also called kala-azar, is the most serious form and is caused by the parasite Leishmania donovani. Patients who develop visceral leishmaniasis can die within months unless they receive treatment. The two main therapies for visceral leishmaniasis are the antimony derivatives sodium stibogluconate (Pentostam®) and meglumine antimoniate (Glucantim®). Sodium stibogluconate has been used for about 70 years and resistance to this drug is a growing problem. In addition, the treatment is relatively long and painful, and can cause undesirable side effects.
Human African Trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease. The parasites concerned are protozoa belonging to the Trypanosoma Genus. They are transmitted to humans by tsetse fly (Glossina Genus) bites which have acquired their infection from human beings or from animals harboring the human pathogenic parasites.
Chagas disease (also called American Trypanosomiasis) is another human parasitic disease that is endemic amongst poor populations on the American continent. The disease is caused by the protozoan parasite Trypanosoma cruzi, which is transmitted to humans by blood-sucking insects. The human disease occurs in two stages: the acute stage, which occurs shortly after infection and the chronic stage, which can develop over many years. Chronic infections result in various neurological disorders, including dementia, damage to the heart muscle and sometimes dilation of the digestive tract, as well as weight loss. Untreated, the chronic disease is often fatal.
The drugs currently available for treating Chagas disease are Nifurtimox and benznidazole. However, problems with these current therapies include their diverse side effects, the length of treatment, and the requirement for medical supervision during treatment. Furthermore, treatment is really only effective when given during the acute stage of the disease. Resistance to the two frontline drugs has already occurred. The antifungal agent Amphotericin b has been proposed as a second-line drug, but this drug is costly and relatively toxic.
In view of the foregoing, it is desirable to develop novel compounds as antiparasitic agents.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides a compound selected from Formula Ia, Ib and Ic:




in which:
n is selected from 0, 1, 2, 3 and 4;
m is selected from 0, 1, 2, 3 and 4;
Ra is selected from hydrogen, halo, —X3NR7R8, —X3OR8, —X3S(O)0-2R8, —X3C(O)NR7R8, —X3R8, benzyl and C6-10aryl optionally substituted with 1 to 3 radicals independently selected from halo, C1-4alkyl, halo-substituted-C1-4alkyl, C1-4alkoxy and halo-substituted-C1-4alkoxy; wherein X3 is selected from a bond and C1-4alkylene;
Rb is selected from hydrogen and C1-4alkyl;
R1 is selected from halo, —OR13, —C(O)OR13, —NR13R14, C6-10aryl and a saturated, unsaturated or partially unsaturated 4-9 member heterocyclic ring containing up to three nitrogens; wherein R13 is selected from hydrogen, C1-6alkyl, halo-substituted-C1-6alkyl, hydroxy-substituted-C1-6alkyl, C6-10aryl-C0-4alkyl, C3-8cycloalkyl-C0-4alkyl, —X1NHC(O)R15, —X1C(NH)NHR15, —X1C(O)NHR15, —X1NHR15, —X1OR15, —C(O)R15 and —C(O)OR15; wherein X1 is selected from a bond and C1-4alkylene; R15 is selected from hydrogen, C1-6alkyl, halo-substituted-C1-6alkyl and benzyl; and R14 is selected from hydrogen, C1-6alkyl and hydroxy-substituted-C1-6alkyl; wherein any aryl or heterocyclic of R1 is optionally substituted with 1-3 radicals independently selected from halo, C1-6alkyl, halo-substituted-C1-6alkyl, C1-6alkoxy and halo-substituted-C1-6alkoxy;
or R13 and R14 together with the nitrogen to which R13 and R14 are attached form a saturated, unsaturated or partially unsaturated 5-9 member heterocyclic ring containing up to three heteroatoms selected from N, NR30, S(O)0-2 and O; wherein R30 is selected from hydrogen and C1-6alkyl; wherein said heterocyclic ring formed by the combination of R13 and R14 is optionally substituted with 1 to 3 radicals independently selected from halo, hydroxy, C1-6alkyl, amino-substituted-C1-6alkyl and halo-substituted-C1-6alkyl;
R2 is selected from hydrogen, C1-6alkyl, amino, C3-8cycloalkyl-C0-4alkyl, C6-10aryl-C0-4alkyl, halo-substituted-C1-6alky, hydroxy-substituted-C1-6alkyl and heterocyclyl-C0-4alkyl; wherein said heterocyclyl is a saturated, unsaturated or partially unsaturated 5-9 member heterocyclic ring containing up to three heteroatoms selected from N, NR30, S(O)0-2 and O; wherein R30 is selected from hydrogen and C1-6alkyl; wherein said C6-10aryl or heterocyclic of R2 is optionally substituted with 1 to 3 radicals independently selected from halo, hydroxy, cyano, nitro, —NHR17, —(CH2)0-2NHC(O)R17, C1-6alkyl, halo-substituted-C1-6alkyl, amino-substituted-C1-6alkyl and C1-6alkoxy; wherein R17 is selected from hydrogen and C1-6alkyl;
R3 is selected from hydrogen, C1-6alkyl, C6-10aryl-C0-4alkyl, —X2C(O)OR16, —X2S(O)0-2R16, —X2OR16, —X2C(O)NHR16 and —X2NHC(O)R16; wherein X2 is selected from a bond and C1-4alkylene; and R16 is selected from hydrogen, C1-6alkyl and C6-10aryl-C0-4alkyl; wherein said aryl of R16 is optionally substituted with 1 to 3 radicals independently selected from halo, C1-6alkyl, halo-substituted-C1-6alkyl, C1-6alkoxy and halo-substituted-C1-6alkoxy;
or R2 and R3 together with the carbon atom to which R2 and R3 are attached forms C3-8cycloalkyl;
or R2 and R13 together with the atoms to which R2 and R13 are attached form a ring selected from C3-8cycloalkyl and a saturated, unsaturated or partially unsaturated 5-9 member mono or fused heterocyclic ring containing up to three heteroatoms or groups selected from N, C(O), NR30, S(O)0-2 and O; wherein R30 is selected from hydrogen and C1-6alkyl; wherein said heterocyclic form the combination of R2 and R13 is optionally substituted with 1 to 3 radicals independently selected from halo, hydroxy, C1-6alkyl and halo-substituted-C1-6alkyl;
R4 is selected from hydrogen and C1-6alkyl;
R5 is selected from hydrogen and C1-6alkyl; or R4 and R5 together with the carbon atom to which R4 and R5 are attached forms C3-8cycloalkyl;
R6 is selected from C6-10aryl, C3-8cycloalkyl and a saturated, unsaturated or partially unsaturated 5-9 member mono or fused heterocyclic ring containing up to three heteroatoms or groups selected from N, C(O), NR30, S(O)0-2 and O; wherein R30 is selected from hydrogen and C1-6alkyl; wherein said aryl or heterocyclic of R6 is optionally substituted by 1 to 3 radicals independently selected from halo, hydroxy, C1-6alkyl and C1-6alkoxy;
R7 is selected from hydrogen and C1-3alkyl;
R8 is selected from C1-10alkyl (straight or branched), C6-10aryl-C0-4alkyl, C3-8cycloalkyl and a saturated, unsaturated or partially unsaturated 5-9 member mono or fused heterocyclic ring containing up to three heteroatoms or groups selected from N, C(O), NR30, S(O)0-2 and O; wherein R30 is selected from hydrogen and C1-6alkyl; wherein said aryl or heterocyclic of R8 is optionally substituted by 1 to 3 radicals independently selected from halo, cyano, hydroxy, C1-6alkyl, halo-substituted-C1-6alkyl, halo-substituted-C1-6alkoxy, C1-6alkoxy, —C(O)OR18, —S(O)0-2R18, —C(O)NHR18, —NHS(O)0-2R18, phenyl and a saturated, unsaturated or partially unsaturated 5-6 member heterocyclic ring containing up to three heteroatoms or groups selected from N, C(O), NR30, S(O)0-2 and O; wherein R30 is selected from hydrogen and C1-6alkyl; wherein said aryl or heterocyclic substituent of R8 is optionally substituted by 1 to 3 radicals independently selected from halo, cyano, hydroxy, C1-6alkyl, halo-substituted-C1-6alkyl and halo-substituted-C1-6alkoxy; wherein R18 is selected from hydrogen and C1-6alkyl;
R9 is selected from hydrogen and C1-6alkyl;
R10 is selected from hydrogen and C1-6alkyl;
R11 is selected from hydrogen and C1-6alkyl;
R12 is selected from hydrogen and C1-6alkyl; or R11 and R12 combine to form C(O); and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixture of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds; with the proviso that the following compounds are excluded from the invention: 2-amino-1-(3-(benzo[d][1,3]dioxol-5-ylamino)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone; 2-(2-methoxyphenyl)-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-phenyl-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-(pyridin-3-yl)-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; and 2-(4-fluorophenyl)-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine.
In a second aspect, the present invention provides a pharmaceutical composition which contains a compound selected from Formula Ia, Ib and Ic or a N-oxide derivative, individual isomers and mixture of isomers thereof; or a pharmaceutically acceptable salt thereof, in admixture with one or more suitable excipients.
In a third aspect, the present invention provides a method of treating a disease in an animal in which a compound of the invention can prevent, inhibit or ameliorate the pathology and/or symptomology of disease caused by a parasite (such as, for example, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malaria, Trypanosoma cruzi or a parasite of the Leishmania genus such as, for example, Leishmania donovani) which method comprises administering to the animal a therapeutically effective amount of a compound selected from Formula Ia, Ib and Ic or a N-oxide derivative, individual isomers and mixture of isomers thereof, or a pharmaceutically acceptable salt thereof.
In a fourth aspect, the present invention provides the use of a compound selected from Formula Ia, Ib and Ic in the manufacture of a medicament for treating a disease caused by a parasite in an animal. The disease may be malaria, leishmaniasis and/or Chagas disease.
In a fifth aspect, the present invention provides a process for preparing compounds selected from Formula Ia, Ib and Ic and the N-oxide derivatives, prodrug derivatives, individual isomers and mixture of isomers thereof, and the pharmaceutically acceptable salts thereof.


DETAILED DESCRIPTION OF THE INVENTION
Definitions
“Alkyl” as a group and as a structural element of other groups, for example halo-substituted-alkyl and alkoxy, can be either straight-chained or branched. C1-4-alkoxy includes, methoxy, ethoxy, and the like. Halo-substituted alkyl includes trifluoromethyl, pentafluoroethyl, and the like.
“Aryl” means a monocyclic or fused bicyclic aromatic ring assembly containing six to ten ring carbon atoms. For example, aryl may be phenyl or naphthyl, preferably phenyl. “Arylene” means a divalent radical derived from an aryl group.
“Heteroaryl” is as defined for aryl where one or more of the ring members are a heteroatom selected from N, O, C(O) and S(O)0-2. For example 5-10 member heteroaryl includes pyridyl, indolyl, indazolyl, quinoxalinyl, quinolinyl, benzofuranyl, benzopyranyl, benzothiopyranyl, benzo[1,3]dioxole, imidazolyl, benzo-imidazolyl, pyrimidinyl, furanyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazolyl, thienyl, etc.
“Cycloalkyl” means a saturated or partially unsaturated, monocyclic, fused bicyclic or bridged polycyclic ring assembly containing the number of ring atoms indicated. For example, C3-10cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.
“Heterocyclic” means cycloalkyl, as defined in this application, provided that one or more of the ring carbons indicated, are replaced by a moiety selected from —O—, —N═, —NR—, —C(O)—, —S—, —S(O)— or —S(O)2—, wherein R is hydrogen, C1-4alkyl or a nitrogen protecting group. For example, 3-8 member heterocycloalkyl as used in this application to describe compounds of the invention includes morpholino, pyrrolidinyl, piperazinyl, piperidinyl, piperidinylone, 1,4-dioxa-8-aza-spiro[4.5]dec-8-yl, etc.
“Halogen” (or halo) represents chloro, fluoro, bromo or iodo.
“Treat”, “treating” and “treatment” refer to a method of alleviating or abating a disease and/or its attendant symptoms. In the present description, the term “treatment” includes both prophylactic or preventative treatment as well as curative or disease suppressive treatment, including treatment of patients at risk of contracting the disease or suspected to have contracted the disease as well as ill patients. This term further includes the treatment for the delay of progression of the disease.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with a parasite. In particular, the compounds can be used to treat malaria, leishmaniasis and/or Chagas disease.
In one embodiment, with reference to compounds of Formula Ia, Ib and Ic: R1 is selected from —OR13, —C(O)OR13, —NR13R14, phenyl, pyridinyl, indolyl, azetidinyl, 1H-indazolyl, piperidinyl and pyrimidinyl; wherein R13 is selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, cyclopropyl, phenyl, benzyl, amino-butyl, hydroxy-ethyl, methoxy-ethyl, butoxy-ethyl, methoxy-propyl, —C(O)R15, —C(O)OR15, —X1OR15, —X1C(NH)NHR15, —X1NHC(O)R15 and X1C(O)NHR15; wherein X1 is selected from a bond and C1-4alkylene; and R15 is selected from hydrogen, methyl, ethyl, propyl, butyl, t-butyl, trifluoromethyl and trifluoromethyl-carbonyl; R14 is selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, isobutyl, hydroxy-ethyl, difluoroethyl and isobutyl; wherein any phenyl, benzyl or heterocyclic of R1 is optionally substituted with 1-3 radicals independently selected from halo, methyl, ethyl, trifluoromethoxy and trifluoromethyl; or R13 and R14 together with the nitrogen to which R13 and R14 are attached form pyrrolidinyl, morpholino, thiomorpholino and piperidinyl; wherein said heterocyclic form the combination of R13 and R14 is optionally substituted with 1 to 3 radicals independently selected from halo, trifluoromethyl, hydroxy and amino-ethyl.
In another embodiment, R2 is selected from hydrogen, methyl, ethyl, isopropyl, propyl, isobutyl, butyl, t-butyl, trifluoromethyl, trifluoro-ethyl, phenyl, benzyl, phenethyl, cyclobutyl-methyl, cyclopentyl, cyclohexyl, cyclohexyl-methyl, hydroxy-methyl and 1-hydroxy-ethyl; wherein said phenyl, benzyl or phenethyl of R2 is optionally substituted with 1 to 3 radicals independently selected from halo, methoxy, trifluoromethyl, hydroxy, amino, nitro, cyano, amino-methyl, methyl-sulfonyl-ethyl, methyl-carbonyl-amino, —NHR17, —CH2NHC(O)R17 and —NHC(O)R17; wherein R17 is selected from hydrogen, ethyl, propyl, butyl and pentyl.
In another embodiment, R3 is selected from hydrogen, methyl, methyl-carbonyl-amino-butyl, propyl-amino-carbonyl-methyl, carboxy-methyl, propyl-amino-carbonyl-methyl, butyl-amino-carbonyl-methyl, pentyl-amino-carbonyl-methyl, propyl-amino-carbonyl-ethyl, trifluoromethyl-carbonyl-amino-butyl, phenyl, benzyl-sulfanyl-methyl, benzoxy-carbonyl-methyl, methyl-sulfonyl-methyl, 1-(benzyloxy)ethyl, benzoxy-carbonyl-ethyl and benzoxy-carbonyl-amino.
In another embodiment, R2 and R3 together with the carbon atom to which R2 and R3 are attached form cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
In another embodiment, R2 and R13 together with the atoms to which R2 and R13 are attached form piperidinyl, cyclobutyl, pyrrolidinyl, morpholino, piperidinyl, tetrahydrofuranyl, tetrahydro-2H-pyran-4-yl, 4-oxoazetidin-2-yl, indolyl, 2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl, 1,2,3,4-tetrahydroisoquinolin-3-yl, oxopiperidin-3-yl or 4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-6-yl.
In a further embodiment, R4, R5, R9 and R10 are independently selected from hydrogen and methyl; R11 and R12 are both hydrogen; or R11 and R12 combine to form C(O).
In a further embodiment, R6 is selected from phenyl, cyclohexyl and pyridinyl; wherein said phenyl or pyridinyl of R6 is optionally substituted by 1 to 3 radicals independently selected from halo, pentyl, hydroxy, methyl and methoxy.
In a further embodiment, R7 is selected from hydrogen, methyl, ethyl and isopropyl; and R8 is selected from phenyl, benzyl, benzo[d][1,3]dioxol-5-yl, cyclobutyl, cyclopentyl, cycloheptyl, cyclohexyl, bicyclo[2.2.1]heptyl, tetrahydro-2H-pyranyl, pyridinyl, piperidinyl, piperazinyl, quinolinyl, pyrrolidinyl and pyrazolyl; wherein said phenyl, benzyl, benzo[d][1,3]dioxol-5-yl, cyclobutyl, cyclopentyl, cycloheptyl, cyclohexyl, bicyclo[2.2.1]heptyl, tetrahydro-2H-pyranyl, pyridinyl, piperidinyl, piperazinyl, quinolinyl, pyrrolidinyl or pyrazolyl of R8 is optionally substituted by 1 to 3 radicals independently selected from halo, cyano, methyl, ethyl, t-butyl, trifluoromethyl, trifluoromethoxy, dimethyl-amino, difluoromethoxy, carboxy, methoxy-carbonyl, methyl-sulfonyl-amino, methyl-sulfonyl, methyl-amino-carbonyl, phenyl, piperidinyl, piperidinyl-methyl, piperazinyl and piperazinyl-methyl.
In another embodiment is a compound of Formula Id:




in which: R1 is —NH2; R2 and R3 are independently selected from hydrogen and methyl; R4 and R5 are independently selected from hydrogen and methyl; R6 is phenyl substituted with a fluoro; and R8 is a phenyl substituted with 1 to 2 radicals independently selected from chloro and fluoro.
In a further embodiment are compounds selected from: 2-amino-1-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone; 2-amino-1-(3-(3,4-difluorophenylamino)-2-(4-fluorophenyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-methylpropan-1-one; and 2-amino-1-(3-(4-chlorophenylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone.
In a further embodiment are compounds selected from: 2-amino-1-{3-[(3,5-dimethylphenyl)amino]-2-phenyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(2H-1,3-benzodioxol-5-ylamino)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-[3-(cyclopentylamino)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(cyclopentylamino)-2-phenyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-2-methyl-1-[2-phenyl-3-(phenylamino)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; methyl 4-{[7-(2-amino-2-methylpropanoyl)-2-phenyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzoate; 2-amino-1-[2-(2-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-{3-[(4-fluorophenyl)amino]-2-phenyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(4-fluorophenyl)amino]-2-(2,4,6-trifluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-[2-(3,5-difluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-{3-[(4-fluorophenyl)amino]-2-(4-pentylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{2-cyclohexyl-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-(pyridin-3-ylamino)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; 4-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]butan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-3-phenylpropan-1-one; (2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-phenylpropan-1-one; 2-amino-1-{3-[(4-bromophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-(dimethylamino)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(benzylamino)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-(4-chlorophenyl)-3-(4-methylphenyl)imidazo[1,2-a]pyrazine; N-{2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}acetamide; N,2-bis(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-[3-(cyclohexylamino)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; N,2-bis(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2,3-bis(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(pyrrolidin-1-yl)ethan-1-one; 3-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(3-fluorophenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(3-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(morpholin-4-yl)ethan-1-one; 4-{2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}-1$1^{6},4-thiomorpholine-1,1-dione; 2-(3,3-difluoropiperidin-1-yl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one; 7-[(1-aminocyclopropyl)carbonyl]-N,2-bis(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-{1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methyl-1-oxopropan-2-yl}acetamide; 2-amino-1-[2-(4-chlorophenyl)-3-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 7-benzyl-N,2-bis(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; benzyl N-{2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}carbamate; 2-amino-3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; 2-amino-1-[2-(4-fluoro-2-hydroxyphenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(4-fluorophenyl)amino]-2-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4-fluorophenyl)amino]-2-(4-methoxyphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-bromophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-chlorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-(3,3-difluoropyrrolidin-1-yl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(3R)-3-fluoropyrrolidin-1-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(3S)-3-fluoropyrrolidin-1-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-2-(4-fluoropiperidin-1-yl)ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[4-(trifluoromethyl)piperidin-1-yl]ethan-1-one; 2-(4,4-difluoropiperidin-1-yl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[3-(trifluoromethyl)piperidin-1-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(3-hydroxypiperidin-1-yl)ethan-1-one; 2-[(2,2-difluoroethyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(3,5-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(3,5-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-(cyclopropylamino)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(2-methylpropyl)amino]ethan-1-one; 2-amino-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-{[4-(trifluoromethyl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-{[4-(trifluoromethyl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-(3,3-difluoropiperidin-1-yl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)ethan-1-one; 1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(3,3-difluoropiperidin-1-yl)ethan-1-one; 1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(methylamino)ethan-1-one; 2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(2,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(2,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxypropan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-phenylethan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]butan-1-one; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(3R)-piperidin-3-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(3S)-piperidin-3-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 7-[2-(diethylamino)ethyl]-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 7-{[(2S)-azetidin-2-yl]carbonyl}-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2R)-pyrrolidin-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2S)-pyrrolidin-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2S)-piperidin-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2R)-piperidin-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(3R)-pyrrolidin-3-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(3S)-pyrrolidin-3-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylethan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylethan-1-one; 1-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}cyclopropan-1-ol; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-3-methylbutan-1-one; N-[(5S)-5-amino-6-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-6-oxohexyl]acetamide; N-[(5S)-5-amino-6-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-6-oxohexyl]-2,2,2-trifluoroacetamide; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxypropan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one; (1S,2S)-2-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}cyclopentan-1-ol; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-phenylpropan-1-one; 2-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxybutan-1-one; (2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-phenylpropan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3,3-dimethylbutan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-phenylpropan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2,2-diphenylethan-1-one; 2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-(trifluoromethyl)butan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-methylpropan-1-one; 1-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}cyclopentan-1-ol; 1-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}cyclohexan-1-ol; (2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-4-phenylbutan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-2,2-dimethyl-3-(4-methylphenyl)propan-1-one; 4,4,4-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-3-methylbutan-1-one; (2S)-2-cyclohexyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-(4-methoxyphenyl)ethan-1-one; 2-(3,5-difluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methoxy-2-phenylethan-1-one; 2-(4-bromophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-[4-(trifluoromethyl)phenyl]ethan-1-one; 3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methoxy-2-phenylpropan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-(3-hydroxyphenyl)ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-(4-hydroxyphenyl)ethan-1-one; 2-(2-chlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one; 2-(4-bromo-2-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one; 2-(4-chlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-4-methylpentan-1-one; (3S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-3-phenylpropan-1-one; 2-(4-fluorophenyl)-N-(4-methylphenyl)imidazo[1,2-a]pyrazin-3-amine; (2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-phenylethan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-phenylethan-1-one; 7-[(1-aminocyclobutyl)carbonyl]-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 7-[(1-aminocyclopentyl)carbonyl]-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 7-[(1-aminocyclohexyl)carbonyl]-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-4,4,4-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]butan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-3-methylpentan-1-one; 2-amino-3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-3-cyclohexyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxypropan-1-one; 2-(benzylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-(dipropylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; (2S)-2-(dipropylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)-3-phenylpropan-1-one; benzyl(4S)-4-{[(tert-butoxy)carbonyl]amino}-5-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-5-oxopentanoate; benzyl(3S)-3-{[(tert-butoxy)carbonyl]amino}-4-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxobutanoate; tert-butyl N-[(5S)-5-{[(benzyloxy)carbonyl]amino}-6-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-6-oxohexyl]carbamate; 2-(cyclopropylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; N-[4-({2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}amino)butyl]acetamide; 2-(4-fluorophenyl)-7-{2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethyl}-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-2,6-diamino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]hexan-1-one; (2S)-2-amino-3-(4-aminophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; N-[(5S)-5-amino-6-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-6-oxohexyl]butanamide; N-[(5S)-5-amino-6-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-6-oxohexyl]-1-(5-{2-oxo-hexahydro-1H-thieno[3,4-d]imidazolidin-4-yl}pentanamido)-3,6,9,12-tetraoxapentadecan-15-amide; N-{4-[(2S)-2-amino-3-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}acetamide; 2-[bis(2-hydroxyethyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; (4S)-4-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}azetidin-2-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxypropan-1-one; 2,2,2-trifluoro-N-[(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-1-oxopropan-2-yl]acetamide; 6-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}-1,2,3,4-tetrahydropyrimidine-2,4-dione; {2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}urea; 1-{2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}guanidine; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(phenylamino)ethan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylbutan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3,3-dimethylbutan-1-one; (3S)-3-amino-4-(4-bromophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]butan-1-one; (3S)-3-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one; 2-(4-chlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; 2-(4-chlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylpropan-1-one; 2-(4-fluorophenyl)-7-{[(6S)-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-6-yl]carbonyl}-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-2-(dimethylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-3-phenylpropan-1-one; 2-[4-(2-aminoethyl)piperidin-1-yl]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-(4-fluorophenyl)-7-[(4-methanesulfonylphenyl)methyl]-N-(4-methylphenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[4-(morpholin-4-yl)phenyl]methyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[4-(4-methylpiperazin-1-yl)phenyl]methyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 7-{[4-(diethylamino)phenyl]methyl}-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; 7-({4-[3-(dimethylamino)propoxy]phenyl}methyl)-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[4-(pyridin-4-yl)phenyl]methyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; tert-butyl N-[(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-(4-propanamidophenyl)propan-2-yl]carbamate; tert-butyl N-[(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-(propylcarbamoyl)propan-2-yl]carbamate; N-{4-[(2S)-2-amino-3-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}propanamide; (4S)-4-amino-5-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-5-oxo-N-propylpentanamide; (3S)-3-amino-4-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxo-N-propylbutanamide; 3-amino-4,4,4-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]butan-1-one; 2-(3-fluorophenyl)-N-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 7-{[(1S,2R)-2-aminocyclopentyl]carbonyl}-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-3,3,3-trifluoropropan-1-one; (2R)-2-amino-3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; N-{4-[(2S)-2-amino-3-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}butanamide; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methoxypropan-1-one; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2R)-oxolan-2-yl]carbonyl}-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2S)-oxolan-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenoxybutan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenoxypropan-1-one; 2-(3-chlorophenoxy)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one; (2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(pyrimidin-4-yl)ethan-1-one; N-(4-chloro-3-fluorophenyl)-2-(3-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methyl-2-(2-methylphenoxy)butan-1-one; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-[(oxan-4-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-2-ethoxy-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(4-hydroxyphenyl)propan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(oxolan-2-yl)ethan-1-one; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-[(oxolan-3-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-2-amino-3-[4-(aminomethyl)phenyl]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; 2-(1-ethylpiperidin-4-yl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(oxolan-3-yl)ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(oxan-2-yl)ethan-1-one; N-(4-chloro-3-fluorophenyl)-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-({4-[(2S)-2-amino-3-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}methyl)butanamide; N-({4-[(2S)-2-amino-3-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}methyl)propanamide; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(piperidin-4-yl)ethan-1-one; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3,3,3-trifluoropropan-1-one; (2R)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-phenylpropan-1-one; (2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-phenylpropan-1-one; (2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylbutan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylbutan-1-one; 2-cyclopentyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(pyridin-4-yl)ethan-1-one; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-(3,5-dichlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-3-methyl-2-phenylbutan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(4-methylphenyl)ethan-1-one; 2-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-hydroxy-3-methylbutan-1-one; 1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-3-methylbutan-1-one; benzyl(3S)-3-{[(tert-butoxy)carbonyl]amino}-4-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-oxobutanoate; benzyl(3S)-3-{[(tert-butoxy)carbonyl]amino}-4-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxobutanoate; tert-butyl N-[(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-nitrophenyl)-1-oxopropan-2-yl]carbamate; tert-butyl N-[(2S)-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(4-nitrophenyl)-1-oxopropan-2-yl]carbamate; (3S)-3-{[(tert-butoxy)carbonyl]amino}-4-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-oxobutanoic acid; (3S)-3-{[(tert-butoxy)carbonyl]amino}-4-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxobutanoic acid; tert-butyl N-[(2S)-3-(4-aminophenyl)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-1-oxopropan-2-yl]carbamate; tert-butyl N-[(2S)-3-(4-aminophenyl)-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxopropan-2-yl]carbamate; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-2,2-dimethylpropan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-2-(hydroxymethyl)-2-methylpropan-1-one; tert-butyl N-[(2S)-3-(3-aminophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxopropan-2-yl]carbamate; tert-butyl N-[(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-1-oxo-3-(propylcarbamoyl)propan-2-yl]carbamate; tert-butyl N-[(2S)-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-(propylcarbamoyl)propan-2-yl]carbamate; 4-{[2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; tert-butyl N-[(2S)-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-(pentylcarbamoyl)propan-2-yl]carbamate; 1-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}-N,N-dimethylpyrrolidin-3-amine; tert-butyl N-[(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-1-oxo-3-(4-pentanamidophenyl)propan-2-yl]carbamate; tert-butyl N-[(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-1-oxo-3-(4-propanamidophenyl)propan-2-yl]carbamate; tert-butyl N-[(2S)-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-(4-pentanamidophenyl)propan-2-yl]carbamate; (3S)-3-amino-4-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-oxo-N-propylbutanamide; (3S)-3-amino-4-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxo-N-propylbutanamide; (3S)-3-amino-4-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxo-N-pentylbutanamide; N-{4-[(2S)-2-amino-3-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-oxopropyl]phenyl}pentanamide; N-{4-[(2S)-2-amino-3-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-oxopropyl]phenyl}propanamide; N-{4-[(2S)-2-amino-3-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}pentanamide; N-{4-[(2S)-2-amino-3-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}propanamide; N-(4-chlorophenyl)-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; 4-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; 4-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; 4-{[2-(4-fluorophenyl)-7-(3-hydroxy-3-methylbutanoyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; 2-(3-methylphenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; tert-butyl N-[(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-[4-(pentylamino)phenyl]propan-2-yl]carbamate; 2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl propanoate; 2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl butanoate; 2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl pentanoate; 2-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-1-(4-fluorophenyl)ethan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-[4-(pentylamino)phenyl]propan-1-one; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[4-(3-methylpiperidin-1-yl)piperidin-1-yl]carbonyl}-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[4-(piperidin-1-yl)piperidin-1-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-7-{[4-(4-fluorophenyl)piperidin-1-yl]carbonyl}-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; ethyl 1-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}piperidine-3-carboxylate; N-[2-(diethylamino)ethyl]-2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazine-7-carboxamide; 2-(3,4-difluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(3-chlorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(2,4-difluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-[(2-hydroxypropyl)amino]-3-phenylpropan-1-one; (2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-[(2-methoxyethyl)amino]-3-phenylpropan-1-one; 3-{[(5R,8S)-2,8-dibenzyl-3-methyl-5-(2-phenylethyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}pyridine; (2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxypropan-1-one; (2R,3S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxybutan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-methanesulfonylbutan-1-one; (3R)-3-amino-4-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxobutanoic acid; (2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methanesulfonylpropan-1-one; (5R,8R)-2,8-dibenzyl-3-methyl-5-(2-phenylethyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; N-[(1S)-2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl]propanamide; N-[(1S)-2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl]butanamide; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-N-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)(methyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)(methyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; (2S)-2-(butylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylethan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(pentylamino)-2-phenylethan-1-one; N-tert-butyl-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; N-[(1S)-2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl]-1-(5-{2-oxo-hexahydro-1H-thieno[3,4-d]imidazolidin-4-yl}pentanamido)-3,6,9,12-tetraoxapentadecan-15-amide; 3-amino-2-(4-fluorophenyl)-7-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-6-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-3-methoxypropan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-2-(pyridin-4-yl)ethan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(1H-indol-1-yl)ethan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-2-(1-ethylpiperidin-4-yl)ethan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(phenylamino)ethan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(1H-indazol-3-yl)ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(propylamino)ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(pentylamino)ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(2-methoxyethyl)amino]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(3-methoxypropyl)amino]ethan-1-one; (2R)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-phenylpropan-1-one; (2S,3S)-2-amino-3-(benzyloxy)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}butan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylbutan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(1,3-thiazol-4-yl)propan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-fluorophenyl)propan-1-one; (2S,3S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylpentan-1-one; (2R)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylbutan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(3,4-difluorophenyl)propan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methyl-2-(methylamino)propan-1-one; 7-{[(2S)-azetidin-2-yl]carbonyl}-N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-methylpentan-1-one; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-[(morpholin-3-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-phenylpropan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-3-cyclobutylpropan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-3,3-dimethylbutan-1-one; (2R)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one; 4-[(2S)-2-amino-3-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-oxopropyl]benzonitrile; 2-(4-fluorophenyl)-6-methyl-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(2,5-difluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(3,4-difluorophenyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-phenyl-2-(phenylamino)ethan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-2-[2-(trifluoromethoxy)phenyl]ethan-1-one; (2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-phenylpropan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-[4-fluoro-3-(trifluoromethyl)phenyl]ethan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-2-phenoxyethan-1-one; 5-({3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}carbonyl)piperidin-2-one; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-{[(2S)-pyrrolidin-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 3-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-4,4,4-trifluorobutan-1-one; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-{[(3S)-pyrrolidin-3-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-methylphenyl)propan-1-one; N-(4-chloro-3-fluorophenyl)-7-[(2,3-dihydro-1H-isoindol-1-yl)carbonyl]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(4-chloro-3-fluorophenyl)-7-{[(2S)-2,3-dihydro-1H-indol-2-yl]carbonyl}-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (3S)-3-amino-4-(4-bromophenyl)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}butan-1-one; (2R)-2-amino-3-(4-bromophenyl)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-{[(4-methoxyphenyl)methyl]sulfanyl}propan-1-one; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-{[(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl]carbonyl}-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4,4,4-trifluorobutan-1-one; 2-(2-butoxyethoxy)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-ethoxy-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(2-methoxyethoxy)ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-6-methyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 5-{[7-(2-amino-2-methylpropanoyl)-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-fluorobenzonitrile; N-(4-methylphenyl)-2-(pyridin-4-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-{[2-chloro-4-(trifluoromethyl)phenyl]amino}-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylbutan-1-one; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-{[(2R)-oxolan-2-yl]carbonyl}-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(1-methyl-1H-indol-3-yl)ethan-1-one; (2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-4-methylpentan-1-one; 1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-3-(2-fluorophenyl)propan-1-one; (2R)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one; 2-[(3-chlorophenyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(4-methylphenyl)amino]ethan-1-one; 2-(4-chloro-3-fluorophenyl)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(4-methoxyphenyl)amino]-2-methylpropan-1-one; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(3,4-dichlorophenyl)ethan-1-one; 2-amino-3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-[(morpholin-2-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-[4-(trifluoromethyl)phenyl]ethan-1-one; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(4-chlorophenyl)ethan-1-one; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-[(quinolin-6-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(4-methylphenyl)amino]-2-phenylethan-1-one; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-[(4-methylmorpholin-2-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(2-fluorophenyl)amino]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methyl-2-(phenylamino)propan-1-one; 2-amino-1-(3-{[4-fluoro-2-(trifluoromethyl)phenyl]amino}-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)-2-methylpropan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methyl-2-(methylamino)butan-1-one; (2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-methyl-2-(methylamino)pentan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-methyl-2-(methylamino)pentan-1-one; 2-amino-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-[(2,6-dimethylphenyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; 2-amino-1-[2-(2-methoxyphenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(4-methylphenyl)amino]-2-(pyridin-4-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(3-chlorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-[(2,4-dimethylphenyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methyl-2-[(4-methylphenyl)amino]propan-1-one; 2-amino-1-[2-(2,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; (2S)-2-[benzyl(methyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)hexan-1-one; 1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(4-methylphenyl)ethan-1-one; (2R)-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)pentan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}butan-1-one; (2R)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-methylpentan-1-one; 2-amino-1-[2-(2,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; (2S)-2-amino-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylbutan-1-one; 2-amino-1-[2-(3-chlorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-2-methyl-1-{3-[(4-methylphenyl)amino]-2-(pyridin-4-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one; 2-(tert-butylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; (2S)-3-(4-chlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)propan-1-one; (2S)-2-amino-3-cyclopropyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2R)-2-(benzylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-(benzylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-2-cyclopropyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; (2S)-2-amino-3-(3,4-difluorophenyl)-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; 1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(4-methylphenyl)amino]propan-1-one; 2-amino-1-[2-(2,5-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(3,4-dichlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; N-(3,4-dichlorophenyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; N-(4-chloro-3-fluorophenyl)-N-ethyl-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methyl-2-(methylamino)butan-1-one; 2-(4-fluorophenyl)-8,8-dimethyl-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(4-chlorophenyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(2,5-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; N-(3,4-difluorophenyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; N-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; 4-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; 4-{[2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; 2-amino-1-{3-[(3,4-difluoro-5-methoxyphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(4-fluoro-3,5-dimethylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; (2S)-2-amino-3-cyclobutyl-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one; (2R)-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one; (2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(1,3-thiazol-4-yl)propan-1-one; (2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-methylphenyl)propan-1-one; (2S)-2-amino-3-(3,4-difluorophenyl)-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one; (2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylbutan-1-one; (2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one; (2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(4-fluorophenyl)ethan-1-one; (2S)-2-amino-2-cyclopropyl-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; (2S)-2-amino-3-cyclopropyl-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one; (2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-methylpentan-1-one; (2S)-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one; 7-{[(2S)-azetidin-2-yl]carbonyl}-N-(3,4-difluorophenyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S,3S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylpentan-1-one; (2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-fluorophenyl)propan-1-one; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-N-(propan-2-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(3-fluorophenyl)-2-(4-fluorophenyl)-N-(propan-2-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-ethyl-N-(3-fluorophenyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylbutan-1-one; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-cyclopropylethan-1-one; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-cyclopropylpropan-1-one; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-cyclobutylpropan-1-one; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-methylpentan-1-one; (2S,3S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylpentan-1-one; (2S)-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one; (2R)-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(4-fluorophenyl)ethan-1-one; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-fluorophenyl)propan-1-one; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-methylphenyl)propan-1-one; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(3,4-difluorophenyl)propan-1-one; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(1,3-thiazol-4-yl)propan-1-one; 7-{[(2S)-azetidin-2-yl]carbonyl}-N-(4-chlorophenyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3,3-dimethylbutan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylbutan-1-one; (2S)-2-amino-2-cyclopropyl-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; (2S)-2-amino-3-cyclopropyl-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-3-cyclobutyl-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-methylpentan-1-one; (2S,3S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylpentan-1-one; (2S)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one; (2R)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one; (2S)-2-amino-2-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; (2S)-2-amino-3-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(4-methylphenyl)propan-1-one; (2S)-2-amino-3-(3,4-difluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]-3-(1,3-thiazol-4-yl)propan-1-one; 7-{[(2S)-azetidin-2-yl]carbonyl}-N,2-bis(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3,3-dimethylbutan-1-one; (2S)-2-amino-3-cyclobutyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-methylpentan-1-one; (2S,3S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylpentan-1-one; (2S)-2-amino-2-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(4-methylphenyl)propan-1-one; (2S)-2-amino-3-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-3-(3,4-difluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(1,3-thiazol-4-yl)propan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-cyclopropylethan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-3-cyclopropylpropan-1-one; (2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one; (2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-2-(4-fluorophenyl)ethan-1-one; (2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-3,3-dimethylbutan-1-one; 2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; N,2-bis(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluoro-3-methylphenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(4-fluoro-3-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-(3-chloro-4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-chloro-3-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(3-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-(4-fluorophenyl)-8,8-dimethyl-3-{[3-(trifluoromethyl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-3-[(3-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; (2S)-2-amino-3-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2,4-dimethylpentan-1-one; (2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-2-methylpropan-1-one; (2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-2-methylpropan-1-one; 3-[(3,4-dichlorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-6-one; 4-{[2-(4-fluorophenyl)-8,8-dimethyl-6-oxo-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; 3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(3-chloro-4-fluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; N-(3-fluorophenyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-8,8-dimethyl-N-[3-(trifluoromethyl)phenyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2,2,2-trifluoro-1-[2-(4-fluorophenyl)-3-[(3-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluoro-3-methylphenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluoro-3-methylphenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-[2-(3-chloro-4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-chloro-3-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-chloro-3-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 5-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-fluorobenzonitrile; 2-fluoro-5-{[2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzoic acid; 2-fluoro-5-{[2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; 5-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-methylbenzonitrile; 5-{[2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-methylbenzoic acid; 5-{[2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-methylbenzonitrile; 2,2,2-trifluoro-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[3-(trifluoromethyl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; tert-butyl N-{1-[3-bromo-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methyl-1-oxopropan-2-yl}carbamate; 2-amino-1-[3-(cyclohexylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(3-chloro-4-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(3-fluoro-4-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 4-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-chlorobenzonitrile; 5-{[2-(4-fluorophenyl)-8,8-dimethyl-6-oxo-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-methylbenzonitrile; N,2-bis(4-fluorophenyl)-5,5,7,8,8-pentamethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-fluoro-5-{[2-(4-fluorophenyl)-8,8-dimethyl-6-oxo-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; 2-(4-fluorophenyl)-5,5,7,8,8-pentamethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-5,5,7,8,8-pentamethyl-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; tert-butyl N-{2-[2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}carbamate; N-(3-fluoro-4-methylphenyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(3-chloro-4-methylphenyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-(4-fluorophenyl)-8,8-dimethyl-3-[(3,4,5-trifluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-fluoro-3-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-3-[(6-methoxypyridin-3-yl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(3-chloro-4-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylpyridin-2-yl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-chloro-4-{[2-(4-fluorophenyl)-8,8-dimethyl-6-oxo-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; (8R)-3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-8-(propan-2-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; (8R)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-(propan-2-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-chloro-3-fluorophenyl)amino]-2-(3,4-difluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; N-(3-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}phenyl)methanesulfonamide; 3-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-N-methylbenzamide; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(3,4,5-trifluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-(4-fluorophenyl)-8,8-dimethyl-N-(3,4,5-trifluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(4-chlorophenyl)-2-(4-fluorophenyl)-6,6,7-trimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; N-(4-chlorophenyl)-2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; (8S)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(1,5-dimethyl-1H-pyrazol-3-yl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-({[(2S)-1-ethylpyrrolidin-2-yl]methyl}amino)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; (8S)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-(propan-2-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; (8S)-3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-8-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; (8R)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; (8R)-3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-8-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-8,8-dimethyl-3-(quinolin-3-ylamino)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-3-[(4-methanesulfonylphenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-8,8-dimethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-8,8-dimethyl-3-({3-[(4-methylpiperazin-1-yl)methyl]phenyl}amino)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-methanesulfonylphenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-(4-fluorophenyl)-8,8-dimethyl-N-[4-(4-methylpiperazin-1-yl)phenyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-[2-(4-fluorophenyl)-6,6-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 5-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-fluorobenzonitrile; 2-(4-fluorophenyl)-6,6-dimethyl-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N,2-bis(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; N-(3,4-difluorophenyl)-2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-fluoro-5-{[2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; 2-(3-fluorophenyl)-7-[(4-methoxyphenyl)methyl]-5,5-dimethyl-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(3,4-dichlorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(4-fluoro-3-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 5-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-methylbenzonitrile; 4-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-chlorobenzonitrile; (2S)-1-[2-(3-fluorophenyl)-5,5-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one; 2-amino-1-[2-(3-fluorophenyl)-5,5-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-[2-(3-fluorophenyl)-5,5-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[(8S)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-(propan-2-yl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[(8R)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[(8S)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 3-[(3-fluoro-4-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; (2S)-1-[2-(3-fluorophenyl)-5,5-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-phenylpropan-1-one; 2-amino-1-{3-[(1,5-dimethyl-1H-pyrazol-3-yl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(1-ethyl-1H-pyrazol-5-yl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[(8R)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-(propan-2-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 3-[(3-fluoro-4-methylphenyl)amino]-2-(3-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(3-chloro-4-methylphenyl)amino]-2-(3-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; N,2-bis(4-fluorophenyl)-7,8,8-trimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(4-chlorophenyl)-2-(4-fluorophenyl)-7,8,8-trimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(4-chlorophenyl)-2-(4-fluorophenyl)-5,5,7-trimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-3-amine; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-5,5,7-trimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(4-chloro-3-methylphenyl)-2-(4-fluorophenyl)-5,5,7-trimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; N-(3,4-difluorophenyl)-2-(4-fluorophenyl)-5,5,7-trimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 5-{[2-(4-fluorophenyl)-5,5,7-trimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-methylbenzonitrile; 3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-7-[(4-methoxyphenyl)methyl]-5,5-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-7-[(4-methoxyphenyl)methyl]-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5,5,7-trimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-5,5,7-trimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-fluoro-3-methylphenyl)amino]-2-(4-fluorophenyl)-5,5,7-trimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-amino-1-{3-[(4-chlorophenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4-fluoro-3-methylphenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4-chloro-3-methylphenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; N-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl)-7,8,8-trimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine; 2-amino-1-{3-[(4-fluoro-3-methylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 5-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-methylbenzonitrile; 2-amino-1-{3-[(3-fluoro-4-methylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-{3-[(3-chloro-4-methylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-(3-{[3-chloro-4-(trifluoromethyl)phenyl]amino}-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)-2-methylpropan-1-one; 2-amino-1-(3-{[4-fluoro-3-(trifluoromethyl)phenyl]amino}-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)-2-methylpropan-1-one; 4-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-(trifluoromethyl)benzonitrile; 5-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-fluorobenzonitrile; 2-amino-1-{3-[(3,4-dimethylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(3-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-{3-[(3-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-{[3-(trifluoromethoxy)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-{3-[(4-ethylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 2-amino-1-(3-{[4-(difluoromethoxy)phenyl]amino}-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-{[4-(trifluoromethoxy)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-{3-[(3,5-dichlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one; 10-[(3,4-difluorophenyl)amino]-11-(4-fluorophenyl)-4,4-dimethyl-3,6,9,12-tetraazatricyclo[7.3.0.0 {2,6}]dodeca-1(12),2,10-trien-5-one; 10-[(3,4-difluorophenyl)amino]-11-(4-fluorophenyl)-4,4-dimethyl-3,6,9,12-tetraazatricyclo[7.3.0.0 {2,6}]dodeca-1(12),10-dien-5-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-phenylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(4-ethylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[4-(trifluoromethoxy)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[3-(trifluoromethoxy)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(3-chlorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[3-(trifluoromethyl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 3-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile; 2-amino-1-{3-[(3,4-dimethylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 4-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-(trifluoromethyl)benzonitrile; 2-amino-1-{3-[(3,5-dimethylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-(3-{[4-fluoro-3-(trifluoromethyl)phenyl]amino}-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)ethan-1-one; 2-amino-1-(3-{[3-chloro-4-(trifluoromethyl)phenyl]amino}-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)ethan-1-one; 2-amino-1-{3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4,4-difluorocyclohexyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-phenylcyclohexyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[4-(trifluoromethyl)cyclohexyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(4-tert-butylcyclohexyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(2-methylcyclohexyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(cycloheptylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(3,3,5-trimethylcyclohexyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(1R,2R,4S)-bicyclo[2.2.1]heptan-2-ylamino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[3-(dimethylamino)pyrrolidin-1-yl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[4-(piperidin-1-yl)piperidin-1-yl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(cyclopentylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(cyclobutylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-(oxan-4-ylamino)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(2-methylbutyl)amino]-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5,5-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-5,5-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4-chlorophenyl)(methyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 7-[2-(dimethylamino)ethyl]-2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 7-[2-(dimethylamino)ethyl]-3-[(3-fluoro-4-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(3-chloro-4-methylphenyl)amino]-7-[2-(dimethylamino)ethyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-6-one; 7-[2-(dimethylamino)ethyl]-3-[(4-fluoro-3-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-chloro-3-methylphenyl)amino]-7-[2-(dimethylamino)ethyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-chloro-3-fluorophenyl)amino]-7-[2-(dimethylamino)ethyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 7-(azetidin-3-ylmethyl)-3-[(4-fluoro-3-methylphenyl)amino]-2-(3-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 7-(2-aminoethyl)-2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-7-(2-hydroxyethyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-6-one; 7-(3-aminopropyl)-3-[(4-fluoro-3-methylphenyl)amino]-2-(3-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-fluoro-3-methylphenyl)amino]-2-(3-fluorophenyl)-7-(3-hydroxypropyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 3-[(4-fluoro-3-methylphenyl)amino]-2-(3-fluorophenyl)-7-(3-methoxypropyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-6-one; 4-{3-[(4-fluoro-3-methylphenyl)amino]-2-(3-fluorophenyl)-8,8-dimethyl-6-oxo-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}butanoic acid; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)methyl]-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylphenyl)methyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-methoxyphenyl)methyl]-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(3,4-difluorophenyl)methyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)methyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylpiperazin-1-yl)methyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(cyclohexylmethyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(4-methylphenyl)propan-1-one; 2-amino-4-(3-fluorophenyl)-1-[2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]butan-1-one; 2-amino-4-(4-chlorophenyl)-1-[2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]butan-1-one; 2-amino-3-cyclohexyl-1-[2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-(4-methylphenyl)-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2,3-bis(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; N,2-bis(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazine-3-carboxamide; 7-(2-aminoacetyl)-N,2-bis(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazine-3-carboxamide; 2-amino-1-[3-(4-fluorophenoxy)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(4-chlorophenoxy)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(3,4-difluorophenoxy)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[3-(4-fluoro-3-methylphenoxy)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylphenyl)sulfanyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(3-fluorophenyl)sulfanyl]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)sulfanyl]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(4-chlorophenyl)sulfanyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(3,5-dimethylphenyl)sulfanyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(3,4-difluorophenyl)sulfanyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(3-fluorobenzene)sulfinyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4-fluorobenzene)sulfinyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H, 8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylbenzene)sulfinyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one; 2-amino-1-{3-[(3,5-dimethylbenzene)sulfinyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(3,4-difluorobenzene)sulfinyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; 2-amino-1-{3-[(4-chlorobenzene)sulfinyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; and 2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylbenzene)sulfonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one.
In an embodiment of the invention are compounds selected from: N-{2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}-3-phenylpropanamide; N-{2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}-3-{8-oxatricyclo[7.4.0.0 {2,7}]trideca-1(9),2,4,6,10,12-hexaen-4-yl}propanamide; N-{2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}-3-(3-phenylpropanamido)propanamide; N-{2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}-3-(3-{8-oxatricyclo[7.4.0.0 {2,7}]trideca-1(9),2,4,6,10,12-hexaen-4-yl}propanamido)propanamide; N-[3-({2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}amino)propyl]-3-phenylpropanamide; 5,5-difluoro-3-(3-(2-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-oxoethylamino)-3-oxopropyl)-7-phenyl-5H-dipyrrolo[1,2-c:1′,2′-f][1,3,2]diazaborinin-4-ium-5-uide; and 5,5-difluoro-2-(3-(6-(2-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-oxoethylamino)-6-oxohexylamino)-3-oxopropyl)-7-(4-methoxyphenyl)-1,3-dimethyl-5H-dipyrrolo[1,2-c:1′,2′-f][1,3,2]diazaborinin-4-ium-5-uide.
In an embodiment of the invention are compounds selected from: N-(4-methylphenyl)-2-(pyridin-3-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyridin-3-amine; 2-cyclohexyl-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-(diphenylmethyl)-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-(2-nitrophenyl)-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-[2-(thiophen-2-yl)phenyl]-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-[2-(difluoromethoxy)phenyl]-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-(2-bromophenyl)-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-{2-[2-(diethylamino)ethoxy]phenyl}-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-[2-(trifluoromethyl)phenyl]-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-(2-{3-[(2,4,4-trimethylpentan-2-yl)amino]imidazo[1,2-a]pyridin-2-yl}phenoxy)ethan-1-ol; 2-[2-(furan-2-yl)phenyl]-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-(4-fluorophenyl)-6-methyl-N-(4-methylphenyl)imidazo[1,2-a]pyridin-3-amine; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyridin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyridin-3-amine; 2-(4-fluorophenyl)-N-(4-methylphenyl)imidazo[1,2-a]pyridin-3-amine; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-amine; 2-(4-fluorophenyl)-6-methyl-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyridin-3-amine; N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-6-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyridin-3-amine; 8-(3,4-difluorophenylamino)-9-(4-fluorophenyl)-2,2-dimethyl-5,6-dihydrodiimidazo[1,2-a:2′,1′-c]pyrazin-3(2H)-one; and 8-(3,4-difluorophenylamino)-9-(4-fluorophenyl)-2,2-dimethyl-1,2,5,6-tetrahydrodiimidazo[1,2-a:2′,1′-c]pyrazin-3(10bH)-one.
In a further embodiment of the invention is a method for treating a Plasmodium related disease in a subject to prevent, inhibit or ameliorate the pathology and/or symptamology of the Plasmodium related disease, comprising administering to a subject, in vivo or in vitro, a therapeutically effective amount of a compound of the invention alone or in combination with a second agent.
In a further embodiment is a method for treating a Plasmodium related disease in a subject to prevent, inhibit or ameliorate the pathology and/or symptamology of the Plasmodium related disease, comprising administering to a subject, in vivo or in vitro, a therapeutically effective amount of a compound alone or in combination with a second agent, wherein the compound is selected from: 2-amino-1-(3-(benzo[d][1,3]dioxol-5-ylamino)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone; 2-(2-methoxyphenyl)-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-phenyl-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; 2-(pyridin-3-yl)-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine; and 2-(4-fluorophenyl)-N-(2,4,4-trimethylpentan-2-yl)imidazo[1,2-a]pyridin-3-amine.
In a further embodiment, the Plasmodium related disease is malaria.
In a further embodiment, the second agent is selected from a kinase inhibitor, an anti-malarial drug and an anti-inflammatory agent. The anti-malarial drug is selected from proguanil, chlorproguanil, trimethoprim, chloroquine, mefloquine, lumefantrine, atovaquone, pyrimethamine-sulfadoxine, pyrimethamine-dapsone, halofantrine, quinine, quinidine, amodiaquine, amopyroquine, sulphonamides, artemisinin, arteflene, artemether, artesunate, primaquine, and pyronaridine.
In a further embodiment, the compounds of the invention can be administered prior to, simultaneously with, or after the second agent.
In a further embodiment, the subject is a human.
Pharmacology and Utility
Compounds of the invention are useful in the treatment and/or prevention of infections such as those caused by Plasmodium falciparum; Plasmodium vivax; Plasmodium ovale; and Plasmodium malaria, trypanosoma cruzi and parasites of the Leishmania genus, such as, for example, Leishmania donovani. 
Malaria is an infectious disease caused by four protozoan parasites: Plasmodium falciparum; Plasmodium vivax; Plasmodium ovale; and Plasmodium malaria. These four parasites are typically transmitted by the bite of an infected female Anopheles mosquito. Malaria is a problem in many parts of the world and over the last few decades the malaria burden has steadily increased. An estimated 1-3 million people die every year from malaria—mostly children under the age of 5. This increase in malaria mortality is due in part to the fact that Plasmodium falciparum, the deadliest malaria parasite, has acquired resistance against nearly all available antimalarial drugs, with the exception of the artemisinin derivatives.
Leishmaniasis is caused by one or more than 20 varieties of parasitic protozoa that belong to the genus Leishmania, and is transmitted by the bite of female sand flies. Leishmaniasis is endemic in about 88 countries, including many tropical and sub-tropical areas.
There are four main forms of Leishmaniasis. Visceral leishmaniasis, also called kala-azar, is the most serious form and is caused by the parasite Leishmania donovani. Patients who develop visceral leishmaniasis can die within months unless they receive treatment. The two main therapies for visceral leishmaniasis are the antimony derivatives sodium stibogluconate (Pentostam®) and meglumine antimoniate (Glucantim®). Sodium stibogluconate has been used for about 70 years and resistance to this drug is a growing problem. In addition, the treatment is relatively long and painful, and can cause undesirable side effects.
Human African Trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease. The parasites concerned are protozoa belonging to the Trypanosoma Genus. They are transmitted to humans by tsetse fly (Glossina Genus) bites which have acquired their infection from human beings or from animals harboring the human pathogenic parasites.
Chagas disease (also called American Trypanosomiasis) is another human parasitic disease that is endemic amongst poor populations on the American continent. The disease is caused by the protozoan parasite Trypanosoma cruzi, which is transmitted to humans by blood-sucking insects. The human disease occurs in two stages: the acute stage, which occurs shortly after infection and the chronic stage, which can develop over many years. Chronic infections result in various neurological disorders, including dementia, damage to the heart muscle and sometimes dilation of the digestive tract, as well as weight loss. Untreated, the chronic disease is often fatal.
The drugs currently available for treating Chagas disease are Nifurtimox and benznidazole. However, problems with these current therapies include their diverse side effects, the length of treatment, and the requirement for medical supervision during treatment. Furthermore, treatment is really only effective when given during the acute stage of the disease. Resistance to the two frontline drugs has already occurred. The antifungal agent Amphotericin b has been proposed as a second-line drug, but this drug is costly and relatively toxic.
The phylum, Apicomplexa, contains many members that are human or animal pathogens including, but not limited to, Plasmodium spp. (Malaria), Toxoplasma gondii (congenital neurological defects in humans), Eimeria spp. (poultry and cattle pathogens), Cryptosporidia (opportunistic human and animal pathogens), Babesia (cattle parasites) and Theileria (cattle parasites). The pathogenesis associated with these parasitic diseases is due to repeated cycles of host-cell invasion, intracellular replication and host-cell lysis. Therefore, understanding parasite proliferation is essential for development of novel drugs and vaccines, for example, to treat malaria.
In vertebrate hosts, the parasite undergoes two main phases of development, the hepathocytic and erythrocytic phases, but it is the erythrocytic phase of its life cycle that causes severe pathology. During the erythrocytic phase, the parasite goes through a complex but well synchronized series of stages, suggesting the existence of tightly regulated signaling pathways.
Calcium serves as an intracellular messenger to control synchronization and development in the erythrocytic life phase. The Plasmodium spp. genomes reveal many sequence identities with calcium binding/sensing protein motifs that include Pf39, calmodulin, and calcium dependent protein kinases (CDPKs). Plasmodium CDPKs, Plasmodium CDPK3 and 4, have been shown to be involved in mosquito infection. CDPK4 has been demonstrated to be essential for the sexual reproduction in the midgut of mosquito by translating the calcium signal into a cellular response and regulating cell cycle progression in the male gametocyte. CDPK3 regulates ookinete gliding motility and penetration of the layer covering the midgut epithelium. P. falciparum CDPK1 (PfCDPK1) is expressed during late schizogony of blood stage and in the infectious sporozoite stage and is secreted to the parasitophorous vacuole by an acylation-dependent mechanism. It can be myristoylated and is abundantly found in detergent-resistant membrane fractions isolated from schizogony-phase parasites. Ontology based pattern identification analysis reveals that PfCDPK1 is clustered with genes associated with either parasite egress or erythrocyte invasion. Direct inhibition of PfCDPK1 can arrest the parasite erythrocytic life cycle progression in the late schizogony phase.
Therefore, kinase activity is distributed in all the stages of P. falciparum parasite maturation and kinase inhibitors of the present invention can be used for treating Plasmodium related diseases. In particular, kinase inhibitors of the present invention can be a route for treating malaria by inhibiting the kinase PfCDPK1. The in vitro cellular assay, infra, can be used to assess the activity of compounds of the invention against a variety of malarial parasite strains.
Compounds of the invention are inactive against mitogen-activated protein kinase-activated protein kinase 2 (MapKap2 or MK-2). For example, 2-amino-1-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone (example 412) and 2-amino-1-(3-(3,4-difluorophenylamino)-2-(4-fluorophenyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-methylpropan-1-one (Example 29) exhibit only 7% and 15% inhibition, respectively, in a single point concentration on this enzyme.
Compounds of the invention are relatively inactive against cannabinoid receptor 1 (CB1). For example, 2-amino-1-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone (example 412) and 2-amino-1-(3-(3,4-difluorophenylamino)-2-(4-fluorophenyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-methylpropan-1-one (Example 29) have an IC50 of 24 μM and greater than 30 μM, respectively.
In accordance with the foregoing, the present invention further provides a method for preventing or treating malaria in a subject in need of such treatment, which method comprises administering to said subject a therapeutically effective amount of a compound selected from Formula Ia, Ib, Ic or a pharmaceutically acceptable salt thereof. The required dosage will vary depending on the mode of administration, the particular condition to be treated and the effect desired.
Administration and Pharmaceutical Compositions
In general, compounds of the invention will be administered in therapeutically effective amounts via any of the usual and acceptable modes known in the art, either singly or in combination with one or more therapeutic agents. A therapeutically effective amount may vary widely depending on the severity of the disease, the age and relative health of the subject, the potency of the compound used and other factors. In general, satisfactory results are indicated to be obtained systemically at daily dosages of from about 0.03 to 2.5 mg/kg per body weight. An indicated daily dosage in the larger mammal, e.g. humans, is in the range from about 0.5 mg to about 100 mg, conveniently administered, e.g. in divided doses up to four times a day or in retard form. Suitable unit dosage forms for oral administration comprise from ca. 1 to 50 mg active ingredient.
Compounds of the invention can be administered as pharmaceutical compositions by any conventional route, in particular enterally, e.g., orally, e.g., in the form of tablets or capsules, or parenterally, e.g., in the form of injectable solutions or suspensions, topically, e.g., in the form of lotions, gels, ointments or creams, or in a nasal or suppository form. Pharmaceutical compositions comprising a compound of the present invention in free form or in a pharmaceutically acceptable salt form in association with at least one pharmaceutically acceptable carrier or diluent can be manufactured in a conventional manner by mixing, granulating or coating methods. For example, oral compositions can be tablets or gelatin capsules comprising the active ingredient together with a) diluents, e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine; b) lubricants, e.g., silica, talcum, stearic acid, its magnesium or calcium salt and/or polyethyleneglycol; for tablets also c) binders, e.g., magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and or polyvinylpyrrolidone; if desired d) disintegrants, e.g., starches, agar, alginic acid or its sodium salt, or effervescent mixtures; and/or e) absorbents, colorants, flavors and sweeteners. Injectable compositions can be aqueous isotonic solutions or suspensions, and suppositories can be prepared from fatty emulsions or suspensions. The compositions may be sterilized and/or contain adjuvants, such as preserving, stabilizing, wetting or emulsifying agents, solution promoters, salts for regulating the osmotic pressure and/or buffers. In addition, they may also contain other therapeutically valuable substances. Suitable formulations for transdermal applications include an effective amount of a compound of the present invention with a carrier. A carrier can include absorbable pharmacologically acceptable solvents to assist passage through the skin of the host. For example, transdermal devices are in the form of a bandage comprising a backing member, a reservoir containing the compound optionally with carriers, optionally a rate controlling barrier to deliver the compound to the skin of the host at a controlled and predetermined rate over a prolonged period of time, and means to secure the device to the skin. Matrix transdermal formulations may also be used. Suitable formulations for topical application, e.g., to the skin and eyes, are preferably aqueous solutions, ointments, creams or gels well-known in the art. Such may contain solubilizers, stabilizers, tonicity enhancing agents, buffers and preservatives.
Compounds of the invention can be administered in therapeutically effective amounts in combination with one or more therapeutic agents (pharmaceutical combinations). Non-limiting examples of compounds which can be used in combination with compounds of the invention are known anti-malarial drugs, for example, proguanil, chlorproguanil, trimethoprim, chloroquine, mefloquine, lumefantrine, atovaquone, pyrimethamine-sulfadoxine, pyrimethamine-dapsone, halofantrine, quinine, quinidine, amodiaquine, amopyroquine, sulphonamides, artemisinin, arteflene, artemether, artesunate, primaquine, pyronaridine, etc.
Where the compounds of the invention are administered in conjunction with other therapies, dosages of the co-administered compounds will of course vary depending on the type of co-drug employed, on the specific drug employed, on the condition being treated and so forth.
The invention also provides for a pharmaceutical combinations, e.g. a kit, comprising a) a first agent which is a compound of the invention as disclosed herein, in free form or in pharmaceutically acceptable salt form, and b) at least one co-agent. The kit can comprise instructions for its administration.
The terms “co-administration” or “combined administration” or the like as utilized herein are meant to encompass administration of the selected therapeutic agents to a single patient, and are intended to include treatment regimens in which the agents are not necessarily administered by the same route of administration or at the same time.
The term “pharmaceutical combination” as used herein means a product that results from the mixing or combining of more than one active ingredient and includes both fixed and non-fixed combinations of the active ingredients. The term “fixed combination” means that the active ingredients, e.g. a compound of Formula I and a co-agent, are both administered to a patient simultaneously in the form of a single entity or dosage. The term “non-fixed combination” means that the active ingredients, e.g. a compound of Formula I and a co-agent, are both administered to a patient as separate entities either simultaneously, concurrently or sequentially with no specific time limits, wherein such administration provides therapeutically effective levels of the 2 compounds in the body of the patient. The latter also applies to cocktail therapy, e.g. the administration of 3 or more active ingredients.
Processes for Making Compounds of the Invention
The present invention also includes processes for the preparation of compounds of the invention. In the reactions described, it can be necessary to protect reactive functional groups, for example hydroxy, amino, imino, thio or carboxy groups, where these are desired in the final product, to avoid their unwanted participation in the reactions. Conventional protecting groups can be used in accordance with standard practice, for example, see T. W. Greene and P. G. M. Wuts in “Protective Groups in Organic Chemistry”, John Wiley and Sons, 1991.
Compounds of Formula I can be prepared by proceeding as in the Reaction Schemes 1-5; R2, R3, R4, R5, R6, R8, R9, R10, R11 and R12 are as defiled in the Summary of the Invention. The following reaction schemes are given to be illustrative, not limiting, descriptions of the synthesis of compounds of the invention:




Reagents and Conditions:
(a) HClO4, MeOH, rt; (b) Pd/C (or PtO2), H2, MeOH, rt; (c) HATU, DIEA, DMF, rt; (d) TFA, DCM, rt




Reagents and Conditions:
(a) HClO4, MeOH, rt; (b) TFA, DCM, rt; (c) Pd2(dba)3, XantPhos, Cs2CO3, Dioxane, 140° C.







Reagents and Conditions:
(a) Cs2CO3, DMF, rt; (b) NH4OAc, Dean-Stark, Toluene, reflux; (c) ethyl 2-bromoacetate, Cs2CO3, DMF, rt; (d) Pd/C, H2, MeOH, rt; (e) LAH or BH3.Me2S, THF, reflux; (f) N-Boc-glycine, HATU, DIEA, DMF, rt; (g) Br2, DCM/AcOH, rt; (h) p-toluidine, Pd2(dba)3, Xantphos, Cs2CO3, Dioxane, 140° C.; (i) TFA, DCM, rt.







Reagents and Conditions:
(a) Cs2CO3, DMF, rt; (b) NH4OAc, Dean-Stark, Toluene, reflux; (c) 3-bromo-2-methylprop-1-ene, Cs2CO3, DMF, rt; (d) microwave, AcOH/MsOH, 210° C.; (e) N-Boc-glycine, HATU, DIEA, DMF, rt; (f) Br2, DCM/AcOH, rt; (g) 4-chloroaniline, Pd2(dba)3, Xantphos, Cs2CO3, Dioxane, 140° C.; (h) 6N HCl, Dioxane, reflux.










Reagents and Conditions:
(a) Cs2CO3, DMF, rt; (b) NH4OAc, Dean-Stark, Toluene, reflux; (c) ethyl 2-bromoacetate, Cs2CO3, DMF, rt; (d) Pd/C, H2, MeOH, rt; (e) PMBCl, KOH, THF, rt; (f) MeI, NaH, DMF, rt; (g) BH3.Me2S, THF, reflux; (h) Br2, DCM/AcOH, rt; (i) p-toluidine, Pd2(dba)3, Xantphos, Cs2CO3, Dioxane, 150° C.; (j) TFA, 70° C.; (k) N-Boc-glycine, HATU, DIEA, DMF, rt; (l) TFA, DCM, rt.
Detailed descriptions of the synthesis of compounds of the Invention are given in the Examples, infra.
Additional Processes for Making Compounds of the Invention
A compound of the invention can be prepared as a pharmaceutically acceptable acid addition salt by reacting the free base form of the compound with a pharmaceutically acceptable inorganic or organic acid. Alternatively, a pharmaceutically acceptable base addition salt of a compound of the invention can be prepared by reacting the free acid form of the compound with a pharmaceutically acceptable inorganic or organic base. Alternatively, the salt forms of the compounds of the invention, for example, fumarate salts, can be prepared using salts of the starting materials or intermediates.
The free acid or free base forms of the compounds of the invention can be prepared from the corresponding base addition salt or acid addition salt from, respectively. For example a compound of the invention in an acid addition salt form can be converted to the corresponding free base by treating with a suitable base (e.g., ammonium hydroxide solution, sodium hydroxide, and the like). A compound of the invention in a base addition salt form can be converted to the corresponding free acid by treating with a suitable acid (e.g., hydrochloric acid, etc.).
Compounds of the invention in unoxidized form can be prepared from N-oxides of compounds of the invention by treating with a reducing agent (e.g., sulfur, sulfur dioxide, triphenyl phosphine, lithium borohydride, sodium borohydride, phosphorus trichloride, tribromide, or the like) in a suitable inert organic solvent (e.g. acetonitrile, ethanol, aqueous dioxane, or the like) at 0 to 80° C.
Prodrug derivatives of the compounds of the invention can be prepared by methods known to those of ordinary skill in the art (e.g., for further details see Saulnier et al., (1994), Bioorganic and Medicinal Chemistry Letters, Vol. 4, p. 1985). For example, appropriate prodrugs can be prepared by reacting a non-derivatized compound of the invention with a suitable carbamylating agent (e.g., 1,1-acyloxyalkylcarbanochloridate, para-nitrophenyl carbonate, or the like).
Protected derivatives of the compounds of the invention can be made by means known to those of ordinary skill in the art. A detailed description of techniques applicable to the creation of protecting groups and their removal can be found in T. W. Greene, “Protecting Groups in Organic Chemistry”, 3rd edition, John Wiley and Sons, Inc., 1999.
Compounds of the present invention can be conveniently prepared, or formed during the process of the invention, as solvates (e.g., hydrates). Hydrates of compounds of the present invention can be conveniently prepared by recrystallization from an aqueous/organic solvent mixture, using organic solvents such as dioxin, tetrahydrofuran or methanol.
Compounds of the invention can be prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds, separating the diastereomers and recovering the optically pure enantiomers. While resolution of enantiomers can be carried out using covalent diastereomeric derivatives of the compounds of the invention, dissociable complexes are preferred (e.g., crystalline diastereomeric salts). Diastereomers have distinct physical properties (e.g., melting points, boiling points, solubilities, reactivity, etc.) and can be readily separated by taking advantage of these dissimilarities. The diastereomers can be separated by chromatography, or preferably, by separation/resolution techniques based upon differences in solubility. The optically pure enantiomer is then recovered, along with the resolving agent, by any practical means that would not result in racemization. A more detailed description of the techniques applicable to the resolution of stereoisomers of compounds from their racemic mixture can be found in Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981.
In summary, the compounds of Formula I can be made by a process, which involves:
(a) that of reaction scheme 1, 2, 3, 4 and/or 5; and
(b) optionally converting a compound of the invention into a pharmaceutically acceptable salt;
(c) optionally converting a salt form of a compound of the invention to a non-salt form;
(d) optionally converting an unoxidized form of a compound of the invention into a pharmaceutically acceptable N-oxide;
(e) optionally converting an N-oxide form of a compound of the invention to its unoxidized form;
(f) optionally resolving an individual isomer of a compound of the invention from a mixture of isomers;
(g) optionally converting a non-derivatized compound of the invention into a pharmaceutically acceptable prodrug derivative; and
(h) optionally converting a prodrug derivative of a compound of the invention to its non-derivatized form.
Insofar as the production of the starting materials is not particularly described, the compounds are known or can be prepared analogously to methods known in the art or as disclosed in the Examples hereinafter.
One of skill in the art will appreciate that the above transformations are only representative of methods for preparation of the compounds of the present invention, and that other well known methods can similarly be used.
EXAMPLES
The present invention is further exemplified, but not limited, by the following Examples (Table 2) and intermediates (Reference compounds Table 1) that illustrate the preparation of compounds of the invention.









TABLE 1







Physical Data




MS (m/z) and/or


Compound
Structure
1H NMR







Ref. comp. 1




[M + H] = 335.2 1H NMR (CDCl3, 400 MHz) δ 7.64 (d, J = 7.2 Hz, 2H), 7.91-7.94 (m, 3H), 7.21-7.27 (m, 3H), 6.59 (d, J = 8.4 Hz, 1H), 6.26 (d, J = 2.0 Hz, 1H), 5.99 (dd, J = 2.0, 9.2 Hz, 1H), 5.83 (s, 2H), 4.48 (s, 2H), 3.89 (s, 2H), 3.38 (s, 2H).


 


Ref. comp. 2




[M + H] = 319.2 1H NMR (CDCl3, 400 MHz) δ 7.34 (s, 2H), 7.10 (s, 2H), 6.79-6.81 (m, 2H), 6.70- 6.74 (m, 1H), 6.40 (br., 1H), 5.19 (s, 2H), 4.22 (s, 2H), 1.98 (s, 6H).


 


Ref. comp. 3




[M + H] = 301.2


 


Ref. comp. 4




[M + H] = 283.2


 


Ref. comp. 5




[M + H] = 291.2


 


Ref. comp. 6




[M + H] = 349.2


 


Ref. comp. 7




[M + H] = 327.2


 


Ref. comp. 8




[M + H] = 309.2


 


Ref. comp. 9




[M + H] = 363.1


 


Ref. comp. 10




[M + H] = 345.1


 


Ref. comp. 11




[M + H] = 379.2


 


Ref. comp. 12




[M + H] = 315.2


 


Ref. comp. 13




[M + H] = 310.2


 


Ref. comp. 14




[M + H] = 315.0


 


Ref. comp. 15




[M + H] = 387.1


 


Ref. comp. 16




[M + H] = 323.2


 


Ref. comp. 17




[M + H] = 327 1H NMR: (300 MHz, DMSO-d6): δ 7.81-7.72 (m, 2H), 7.11 (m, 2H), 6.97 (m, 2H,), 6.56-6.52 (m, 2H), 3.86 (s, 2H), 3.55 (m, 2H), 3.02 (m, 2H)


 


Ref. comp. 18




[M + H] = 311.9


 


Ref. comp. 19




[M + H] = 229 1H NMR (300 MHz, CDCl3): δ 8.82 (s, 1H), 8.28 (d, J = 4.8 Hz, 1H) 8.05-8.09 (m, 2H) 7.76 (d, J = 4.5 Hz, 1H) 7.27- 7.33 (m, 2H) 5.79 (s, 2H)


 


Ref. comp. 20




[M + H] = 327.2


 


Ref. comp. 21




[M + H] = 324.3


 


Ref. comp. 22




[M + H] = 343.2


 


Ref. comp. 23




[M + H] = 323.2


 


Ref. comp. 24




[M + H] = 339.1


 


Ref. comp. 25




[M + H] = 387.1


 


Ref. comp. 26




[M + H] = 343.2


 


Ref. comp. 27




[M + H] = 345.1


 


Ref. comp. 28




[M + H] = 377.1


 


Ref. comp. 29




[M + H] = 323 1H NMR (400 MHz, CD3OD) δ 7.73 (d, J = 6.8 Hz, 2H), 7.00-6.99 (m, 4H), 6.49 (d, J = 8.0 Hz, 2H), 4.01 (s, 2H), 3.72 (s, 2H), 3.15 (s, 2H), 2.19 (s, 3H).


 


Ref. comp. 30




[M + H] = 343 1H NMR-: (300 MHz, DMSO-d6): δ 7.94 (s, 1H), 7.80-7.74 (m, 2H), 7.18-7.09 (m, 4H), 6.56 (d, J = 8.7 Hz, 2H), 3.87 (s, 2H), 3.55 (s, 2H), 3.02 (t, J = 5.4 Hz, 2H).


 


Ref. comp. 31




[M + H] = 341 1H NMR (300 MHz, CDCl3) δ 7.70-7.62 (m, 1H), 7.01 (d, J =  8.1 Hz, 2H), 6.92- 6.76 (m, 2H), 6.52 (d, J =  8.1 Hz, 2H), 5.33 (s, 1H), 4.23 (s, 2H), 3.77 (m, 2H), 3.26 (m, 2H), 2.25 (s, 3H).


 


Ref. comp. 32




[M + H] = 229 1H NMR (300 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.30-8.28 (m, 1H), 7.89-7.76 (m, 3H), 7.54- 7.47 (m, 1H), 7.12-7.17 (m, 1H), 5.94 (s, 2H).


 


Ref. comp. 33




[M + H] = 243.1


 


Ref. comp. 34




[M + H] = 452.2


 


Ref. comp. 35




[M + H] = 482 1H-NMR: (400 MHz, CD3OD) δ 7.84-7.81 (m, 2H), 7.14 (t, J =  8.8 Hz, 2H), 4.09- 4.01 (m, 4H), 3.81 (t, J = 4.8 Hz, 2H), 1.89 (s, 6H), 1.46 (s, 9H).


 


Ref. comp. 36




[M + H] = 515.0


 


Ref. comp. 37




[M + H] = 452.2


 


Ref. comp. 38




[M + H] = 243 1H NMR: (300 MHz, DMSO-d6) δ 8.79 (d, J = 0.9 Hz, 1H), 8.26- 8.24 (m, 1H), 7.93-7.86 (m, 1H), 7.85-7.83 (m, 1H), 7.74 (d, J = 4.8 Hz, 1H), 7.21 (t, J = 9.3 Hz, 1H), 5.80 (s, 2H), 2.29 (d, J = 13.5 Hz, 3H


 


Ref. comp. 39




[M + H] = 263 1H NMR (300 MHz, DMSO-d6): δ 8.83 (d, J =  1.2 Hz, 1H), 8.30- 8.28 (m, 1H), 8.18-8.15 (m, 1H), 8.06-8.00 (m, 1H), 7.78 (d, J = 4.5 Hz, 1H), 7.51 (d, J =  9 Hz, 1H), 5.91 (s, 2H)


 


Ref. comp. 40




[M + H] = 263 1H NMR-: (300 MHz, DMSO-d6): δ 8.84 (1H, d, J = 1.2 Hz), 8.30- 8.28 (1H, m), 7.99-7.88 (2H, m), 7.77 (1H, d, J = 4.8 Hz), 7.66 (1H, t, J = 8.1 Hz), 6.01 (2H, s)


 


Ref. comp. 41




[M + H] = 260 1H NMR: (300 MHz, CDCl3) δ 7.75-7.70 (m, 2H), 7.10-7.03 (m, 3H), 3.89 (s, 2H), 3.78 (s, 2H), 2.43 (s, 3H), 1.19 (s, 6H)


 


Ref. comp. 42




[M + H] = 481.0


 


Ref. comp. 43




[M + H] = 445.0


 


Ref. comp. 44




1H NMR: (400 MHz, CDCl3) δ 7.88-7.92 (m, 2H), 7.07-7.11 (m, 2H), 4.88 (s, 1H), 4.87 (s, 2H), 3.84 (s, 1H), 1.55 (s, 6H), 1.51 (s, 6H), 1.37 (s, 9H) 


 


Ref. comp. 45




[M + H] = 351.2


 


Ref. comp. 46




[M + H] = 338.0


 


Ref. comp. 47




[M + H] = 458.0


 


Ref. comp. 48




1H NMR: (400 MHz, CDCl3) δ 7.65-7.69 (m, 2H), 7.14 (s, 1H) 7.03 (t, J = 8.8 Hz, 2H), 4.62 (s, 2H), 3.11 (s, 3H), 1.70 (m, 6H)


 


Ref. comp. 49




[M + H] = 481.1


 


Ref. comp. 50




1H NMR: (400 MHz, CDCl3 7.87-7.90 (m, 2H), 7.07 (t, J = 8.8 Hz, 2H), 3.86 (t, J = 5.6 Hz, 2H), 3.03 (t, J = 5.6 Hz, 2H), 2.44 (s, 3H), 1.50 (s, 6H)


 


Ref. comp. 51




[M + H] = 232 1H NMR (300 MHz, DMSO-d6) δ 4.47 (s, 2H), 4.65 (s, 2H), 7.15-7.21 (m, 2H), 7.55 (s, 1H), 7.74-7.79 (m, 2H), 8.48 (s, 1H)


 


Ref. comp. 52




[M + H] = 277.0 1H NMR: (400 MHz, CD3OD) δ 7.12- 7.07 (m, 2H), 4.95 (t, J = 2.0 Hz, 2H), 4.57 (t, J =  2.00 Hz, 2H).


 


Ref. comp. 53




[M + H] = 306 1H NMR: (300 MHz, CDCl3): δ 8.44- 8.46 (m, 2H), 7.79 (m, 2H), 7.06-7.09 (d, J = 8.1 Hz, 2H), 6.60- 6.63 (d, J =  8.4 Hz, 2H), 5.57 9s, 1H), 3.90 9s, 2H), 3.81 (m, 2H), 3.43 9s, 1H), 3.03 (m, 2H), 2.29 (s, 3H)


 


Ref. comp. 54




[M + H] = 335 1H NMR: (300 MHz, CDCl3): δ 7.67 (d, J = 6 Hz, 1H), 7.25 (d, J =  6.6 Hz, 1H), 7.01 (t, J = 4.2 Hz, 2H), 6.94 (t, J = 8.1 Hz, 2H), 6.52 (d, J =  8.1 Hz, 2H), 5.87 (s, 1H), 4.20 (s, 2H), 3.83 (s, 3H), 3.75 (m, 2H), 3.49 (s, 1H), 3.22 (m, 2H), 2.24 (s, 3H)


 


Ref. comp. 55




[M + H] = 338 1H NMR: (300 MHz, DMSO-d6) δ 8.76 (s, 1H), 7.94-7.89 (m, 2H), 7.31-7.25 (m, 2H), 4.57 (s, 2H), 1.56 (s, 6H).


 


Ref. comp. 56




1H NMR: (400 MHz, CD3OD) δ 7.61- 7.57 (m, 2H), 7.16 (s, 1H); 7.00-6.96 (m, 2H), 3.96 (t, J = 5.2 Hz, 2H), 3.77 (t, J = 5.2 Hz, 2H), 1.76 (s, 6H), 1.42 (s, 9H)


 


Ref. comp. 57




[M + H] = 302.2


 


Ref. comp. 58




[M + H] = 274 1H NMR: (300 MHz, CDCl3): δ 7.73- 7.78 (m, 2H), 7.06-7.13 (m, 3H), 6.73 (s, 1H), 4.77 (s, 2H), 4.72 (s, 1H), 2.51- 2.58 (m, 1H), 1.09-1.12 (d, J = 6.9 Hz, 3H), 0.87- 0.91 (d, J =  6.9 Hz, 3H)


 


Ref. comp. 59




[M + H] = 278 1H NMR: (300 MHz, CDCl3): δ 7.60- 7.64 (m, 1H), 7.42-7.60 (m, 1H), 7.12-7.22 (m, 1H), 7.08 (s, 1H), 6.94 (s, 1H), 4.72 (s, 2H)


 


Ref. comp. 60




1H NMR: (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 7.75-7.79 (m, 2H), 7.54 (s, 1H), 7.16-7.22 (m, 2H), 4.62-4.73 (m, 3H), 1.51 (d, J = 6.3 Hz, 3H)


 


Ref. comp. 61




[M + H] = 274 1H NMR (300 MHz, CDCl3): δ 7.76- 7.71 (m, 2H), 7.12 (m, 3H), 6.61 (s, 1H), 4.71 (s, 3H), 2.53- 2.48 (m, 1H), 1.11-1.08 (m, 3H), 0.91-0.88 (m, 3H).


 


Ref. comp. 62




[M + H] = 246 1H NMR (300 MHz, DMSO-d6): δ 8.60 (s, 1H), 7.80-7.74 (m, 2H), 7.54 (s, 1H), 7.23-7.15 (m, 2H), 4.73-4.61 (m, 3H), 1.51 (d, J = 6.3 Hz, 3H,)


 


Ref. comp. 63




[M + H] = 496 1H NMR (300 MHz, CDCl3) 5.62-5.65 (m, 1H), 5.39 (s, 1H), 5.02- 5.07 (m, 1H), 4.62 (m, 1H), 3.77-4.11 (m, 6H), 3.35-3.39 (m, 1H), 2.31 (s, 1H), 1.47 (s, 9H), 1.26- 1.34 (m, 3H), δ 0.88- 1.13 (m, 3H),


 


Ref. comp. 64




[M + H] = 467 1H NMR: (300 MHz, CDCl3) δ 7.88-7.92 (t, J = 6.6 Hz, 2H), 7.10- 7.15 (m, 2H), 5.41-5.51 (m, 1H), 5.02-5.19 (m, 2H), 4.05- 4.11 (m, 4H), 3.70-3.88 (m, 2H), 3.30 (m, 1H), 1.71-1.74 (m, 2H), 1.61- 1.63 (m, 1H), 1.47 (s, 9H)


 


Ref. comp. 65




[M + H] = 467 


 


Ref. comp. 66




[M + H] = 496 1H NMR: (300 MHz, DMSO-d6): δ 7.93-7.86 (m, 2H), 7.31-7.25 (m, 2H), 6.89 (s, 1H), 5.30-5.16 (m, 1H), 4.75-4.65 (m, 1H), 4.35- 4.26 (m, 1H), 3.99-3.66 (m, 4H), 2.28-2.15 (m, 1H), 1.62-1.39 (m, 10 H), 1.01-0.88 (m, 3H).


 


Ref. comp. 67




[M + H] = 338 1H NMR (300 MHz, DMSO-d6) δ 8.76 (s, 1H), 7.78 (m, 1H), 7.65 (m, 1H), 7.53-7.45 (m, 1H), 7.18-7.12 (m, 1H), 4.58 (s, 1H),  1.58 (s, 6H)


 


Ref. comp. 68




[M + H] = 345 1H NMR: (300 MHz, CDCl3) δ 7.76-7.72 (m, 2H) 7.08-6.99 (m, 3H) 6.50-6.43 (m, H) 6.38-6.35 (m, 1H) 5.26 (s, H), 4.17 (s, 2H) 3.73-3.69 (m, 2H) 3.27-3.23 (m, 2H) 2.05 (s, 2H)


 


Ref. comp. 69




[M + H] = 361 1H NMR (300 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.58 (d, J =  7.8 Hz, 1H), 7.48 (d, J = 7.2 Hz, 1H), 7.28-7.38 (m, 2H), 6.94- 7.00 (m, 1H), 6.42-6.52 (m, 2H), 3.88 (s, 2H), 3.57 (s, 2H), 3.04 (t, J = 5.1 Hz, 2H)


 


Ref. comp. 70




[M + H] = 361 1H NMR (400 MHz, CDCl3) δ 7.75-7.70 (m, 2H) 7.25-7.19 (m, H), 7.05-7.02 (m, 2H), 6.48-6.41 (m, 2H), 4.16 (s, 2H), 3.70 (m, 2H), 3.24 (m, 2H).









Reference Compound 1
N-(benzo[d][1,3]dioxol-5-yl)-2-phenyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-amine




Reference Compound 1 was prepared in the following way:




A stirred solution of Compound 1-1 (685 mg, 10 mmol) in 10 mL of ethyl formate was heated to 120° C. for 2 hours in a microwave oven. Solvent was removed and the residue was subjected to MS-triggered HPLC purification to give 728 mg of Compound 1-2 as brown oil after neutralization. To a solution of Compound 1-2 (728 mg, 4.4 mmol) in 20 mL of DCM were added DIEA (2.30 mL, 13.2 mmol) and POCl3 (0.45 mL, 4.84 mmol) at 0° C. The reaction mixture was stirred at the same temperature for 2 hours and at room temperature for 2 additional hours. Solvent was removed and the residue was subjected to MS-triggered HPLC purification to give 281 mg of Compound 1-3 as yellow solid after neutralization: 1H NMR (CDCl3, 400 MHz) δ 6.88 (dd, J=2.0, 8.4 Hz, 1H), 6.79 (d, J=1.6 Hz, 1H), 6.74 (d, J=8.4 Hz, 1H), 6.01 (s, 2H).




To a stirred solution of compound Compound 1-3 (158 mg, 1.66 mmol) in 10 mL of MeOH were added benzaldehyde (0.25 mL, 2.49 mmol), 2-aminopyrazine (281 mg, 1.91 mmol), and followed by 1.0 N HClO4 in MeOH (0.17 mL, 0.17 mmol). The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was directly taken to mass-triggered HPLC purification. The collected MeCN/water solution was concentrated and dried on a lyophilizer to give 296 mg of Compound 1-4 as powdery product: 1H NMR (CDCl3, 400 MHz) δ 9.23 (d, J=1.2 Hz, 1H), 8.03 (d, J=4.8 Hz, 1H), 7.91-7.94 (m, 3H), 7.26-7.44 (m, 3H), 6.68 (d, J=8.4 Hz, 1H), 6.32 (br, 1H), 6.25 (d, J=2.4 Hz, 1H), 6.00 (dd, J=2.4, 8.4 Hz, 1H), 5.93 (s, 2H).




To a stirred solution of Compound 1-4 (181 mg, 0.54 mmol) in 10 mL of MeOH was added Pd/C (58 mg, 0.054 mmol). The reaction mixture was evacuated and back filled with H2. The reaction mixture was stirred at room temperature overnight. The solid was filtered off and solvent was removed. 400 MHz proton NMR of the crude product proved it to be the title compound: 1H NMR (CDCl3, 400 MHz) δ 7.64 (d, J=7.2 Hz, 2H), 7.91-7.94 (m, 3H), 7.21-7.27 (m, 3H), 6.59 (d, J=8.4 Hz, 1H), 6.26 (d, J=2.0 Hz, 1H), 5.99 (dd, J=2.0, 9.2 Hz, 1H), 5.83 (s, 2H), 4.48 (s, 2H), 3.89 (s, 2H), 3.38 (s, 2H).
The following reference compounds were prepared by the same three component Ugi reaction used to prepare Reference Compound 1, using appropriate starting materials, followed by a Pd/C mediated hydrogenation: Reference Compound 2 was prepared from 2-aminopyridine, benzaldehyde and 1-isocyano-3,5-dimethylbenzene; Reference Compound 3 was prepared from 2-aminopyrazine, 4-fluorobenzaldehyde and isocyanocyclopentane; Reference Compound 4 was prepared from 2-aminopyrazine, benzaldehyde and isocyanocyclopentane; Reference Compound 5 was prepared from 2-aminopyrazine, benzaldehyde and isocyanobenzene; Reference Compound 6 was prepared from 2-aminopyrazine, benzaldehyde and methyl 4-isocyanobenzoate; Reference Compound 7 was prepared from 2-aminopyrazine, 2-fluorobenzaldehyde and 1-fluoro-4-isocyanobenzene; Reference Compound 8 was prepared from 2-aminopyrazine, benzaldehyde and 1-fluoro-4-isocyanobenzene; Reference Compound 9 was prepared from 2-aminopyrazine, 2,4,6-trifluorobenzaldehyde and 1-fluoro-4-isocyanobenzene; Reference Compound 10 was prepared from 2-aminopyrazine, 3,5-difluorobenzaldehyde and 1-fluoro-4-isocyanobenzene; Reference Compound 11 was prepared from 2-aminopyrazine, 4-pentylbenzaldehyde and 1-fluoro-4-isocyanobenzene; Reference Compound 12 was prepared from 2-aminopyrazine, cyclohexanecarbaldehyde and 1-fluoro-4-isocyanobenzene; Reference Compound 13 was prepared from 2-aminopyrazine, 4-fluorobenzaldehyde and 3-isocyanopyridine; Reference Compound 14 was prepared from 2-aminopyrazine, 4-fluorobenzaldehyde and isocyanocyclohexane; Reference Compound 15 was prepared from 2-aminopyrazine, 4-fluorobenzaldehyde and 1-bromo-4-isocyanobenzene; Reference Compound 16 was prepared from 2-aminopyrazine, 4-fluorobenzaldehyde and (isocyanomethyl)benzene; Reference Compound 17 was prepared from 2-aminopyrazine, 4-fluorobenzaldehyde and isocyanofluoro)benzene; Reference Compound 22 was prepared from 2-aminopyrazine, 4-fluoro-2-hydroxy benzaldehyde and 1-fluoro-4-isocyanobenzene; Reference Compound 23 was prepared from 2-aminopyrazine, 4-methylbenzaldehyde and 1-fluoro-4-isocyanobenzene; Reference Compound 24 was prepared from 2-aminopyrazine, 4-methoxybenzaldehyde and 1-fluoro-4-isocyanobenzene; Reference Compound 25 was prepared from 2-aminopyrazine, 4-bromobenzaldehyde and 1-fluoro-4-isocyanobenzene; Reference Compound 26 was prepared from 2-aminopyrazine, 4-chlorobenzaldehyde and 1-fluoro-4-isocyanobenzene; and Reference Compound 29 was prepared from 2-aminopyrazine, 4-fluorobenzaldehyde and 1-methyl-4-isocyanobenzene.
Reference Compound 18
2,3-bis(4-fluorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine




Reference Compound 18 was prepared by the following way:




To a solution of 2-(4-fluorophenyl)acetic acid (1.54 g, 10 mmol) in 30 mL dry DCM was added slowly SOCl2 (2.18 mL, 30 mmol), 2 drops of DMF was added. The reaction mixture was stirred at reflux for 1 hour before the solvent was removed. The residue was dissolved in 30 mL of DCM and AlCl3 (2.67 g, 22 mmol) was added at 0° C. The reaction mixture was stirred at room temperature for 10 mins. Fluorobenzene (0.94 mL, 10 mmol) in 2 mL of DCM was added dropwise at 0° C. The reaction mixture was allowed to stir at the same temperature for 2 hours. The reaction mixture was poured into a mixture of 30 mL of 0.1M HCl and 50 g crushed ice. The resulting mixture was separated and the aqueous layer was washed with DCM. The combined DCM solution was dried and concentrated. The residue was subjected to flash chromatography purification to give 983 mg of Compound 18-1 as light yellow solid: 1H NMR (CDCl3, 400 MHz) δ 8.04-8.08 (m, 2H), 7.23-7.26 (m, 2H), 7.15 (t, J=8.8 Hz, 2H), 7.04 (t, J=8.8 Hz, 2H), 4.26 (s, 2H).




To a solution of Compound 18-1 (232 mg, 1.0 mmol) in 6 mL of DCM was added Br2 (61 μL, 1.2 mmol) in 12 mL of acetic acid. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was directly subjected to mass-triggered HPLC purification to give 181 mg yellow solid. The mass of the desired product on preparative HPLC was not right and did not show the characteristic peak pattern of bromides. The peak was collected by that mass and the compound was verified to be the right mass on the analytical HPLC, and also by 400 MHz proton NMR: 1H NMR (CDCl3, 400 MHz) δ 8.02-8.05 (m, 2H), 7.51-7.54 (m, 2H), 7.10-7.15 (m, 2H), 7.04-7.08 (m, 2H), 6.31 (s, 1H).




A solution of 2-aminopyrazine (57 mg, 0.60 mmol), Compound 18-2 (156 mg, 0.50 mmol) and K2CO3 (83 mg, 0.60 mmol) in 5 mL of EtOH was stirred at 120° C. for 3 hours. Solvent was removed and the residue was subjected to MS-triggered HPLC purification. The collected MeCN/water solution was neutralized. The organic solution was dried and concentrated to give Compound 18-3 as yellow oil: 1H NMR (CDCl3, 400 MHz) δ 9.14 (d, J=1.2 Hz, 1H), 7.86 (d, J=1.6 Hz, 2H), 7.62-7.65 (m, 2H), 7.42-7.45 (m, 2H), 7.28 (t, J=8.4 Hz, 2H), 7.02 (t, J=8.8 Hz, 2H), 6.31 (s, 1H).




To a stirred solution of Compound 18-3 (10 mg, 0.033 mmol) in 6 mL of MeOH was added Pd/C (4 mg, 0.0033 mmol). The reaction mixture was evacuated and back filled with H2. The reaction mixture was stirred at room temperature overnight. The solid was filtered off and solvent was removed. The product was subjected to mass-triggered HPLC purification to give the title compound as yellow oil after neutralization.
Reference Compound 19
2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine




Reference Compound 19 was prepared by the following way:




To a stirred solution of 2-aminopyrazine (571 mg, 6.0 mmol) in 10 mL of MeOH were added 4-fluorobenzaldehyde (0.97 mL, 9.0 mmol), 2-isocyano-2-methylpropane (0.78 mL, 6.9 mmol), and followed by 1.0 N HClO4 in MeOH (0.60 mL, 0.60 mmol). The reaction mixture was stirred at room temperature for 3 hours. Solvent was removed and the residue was subjected to flash chromatography purification to give Compound 19-1 as white solid: 1H NMR (CDCl3, 400 MHz) δ 8.97 (d, J=1.6 Hz, 1H), 8.10 (dd, J=1.6, 4.4 Hz, 1H), 7.90-7.94 (m, 2H), 7.13 (t, J=8.8 Hz, 2H), 1.04 (s, 9H).




A solution of Compound 19-1 (284 mg, 1.0 mmol) in 10 mL of 4:1 DCM and TFA was stirred at room temperature for 2 hours. Solvent was removed and the product was directly used in the next step after neutralization.
Reference Compound 20
N-(3-fluorophenyl)-2-(4-fluorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-amine




Reference Compound 20 was prepared by the following way: to a solution of Reference Compound 19 (69 mg, 0.30 mmol) in 6 mL of dioxane were added 1-bromo-3-fluorobenzene (66 μL, 0.60 mmol), Pd2(dba)3 (8 mg, 0.009 mmol), Xantphos (11 mg, 0.018 mmol) and Cs2CO3 (196 mg, 0.60 mmol) at room temperature. The reaction mixture was degassed and stirred at 120° C. under N2 for 5 hours. The reaction mixture was cooled to room temperature and solid was filtered off. The resulting filtrate was concentrated. The residue was subjected to mass-triggered HPLC purification to give a yellow oil after neutralization. To a stirred solution of the obtained adduct (64 mg, 0.20 mmol) in 5 mL of MeOH was added Pd/C (21 mg, 0.02 mmol). The reaction mixture was evacuated and back filled with H2. The reaction mixture was stirred at room temperature overnight. The solid was filtered off and solvent was removed. The residue was subjected to mass-triggered HPLC purification to give a yellow solid.
Reference Compound 27 was prepared from Reference Compound 19 by an amination reaction with 1-bromo-3,5-difluorobenzene followed by a Pd/C mediated hydrogenation; Reference Compound 28 was prepared from Reference Compound 19 by an amination reaction with 1-bromo-4-(trifluoromethyl)benzene followed by a Pd/C mediated hydrogenation; Reference Compound 30 was prepared from Reference Compound 19 by an amination reaction with 1-bromo-4-(trifluoromethyl)benzene followed by a Pd/C mediated hydrogenation; Reference Compound 31 was prepared from Reference Compound 11 by an amination reaction with 1-bromo-2,4-difluorobenzene followed by a Pd/C mediated hydrogenation; Reference Compound 32 was prepared by the same way that Reference Compound 19 was prepared: a three component Ugi reaction among 2-aminopyrazine, 3-fluorobenzaldehyde and 2-isocyano-2-methylpropane followed by a TFA mediated deprotection; Reference Compound 34 was prepared by a three component Ugi reaction among 2-aminopyrazine, 3-fluorobenzaldehyde, and 2-isocyano-2-methylpropane followed by a HATU mediated amidation reaction with 2-(benzyloxycarbonylamino)-2-methylpropanoic acid and HCl mediated deprotection.
Reference Compound 33
2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyrazin-3-amine




Reference Compound 33 was prepared by the same way that Reference Compound 1 was prepared:




To a stirred solution of 5-bromopyrazin-2-amine (313 mg, 1.8 mmol) in 20 mL of MeOH were added 4-fluorobenzaldehyde (191 μL, 1.8 mmol), and followed by 1.0 N HClO4 in MeOH (0.15 mL, 0.15 mmol). The reaction mixture was stirred at room temperature for 0.5 hour which was followed by addition of 2-isocyano-2-methylpropane (170 μL, 1.5 mmol). The stirring was continued at room temperature overnight. The reaction mixture was subjected to direct mass-triggered HPLC purification to give 299 mg of Compound 33-1 as a yellow solid.




To a stirred solution of Compound 33-1 (131 mg, 0.36 mmol) in 10 mL of dioxane were added 2.0 M Me2Zn in toluene (0.75 mL, 1.5 mmol) and Ni(DPPP)2Cl2 (98 mg, 0.18 mmol). The reaction mixture was evacuated and back filled with N2. The reaction mixture was stirred at reflux overnight. Reaction mixture was quenched with methanol. Solid was filtered off and solvent was removed. The residue was subjected to mass-triggered HPLC purification to give Compound 33-2 as yellow oil.




To a solution of Compound 33-2 (9 mg, 0.03 mmol) in 2 mL of DCM was added 4 mL of TFA. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was subjected to mass-triggered HPLC purification to give the titled compound in quantitative yield after neutralization.
Reference Compound 35
2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyrazin-3-amine




Reference Compound 35 was prepared by the following way:




To a solution of 2-bromo-1-(4-fluorophenyl)ethanone (46.5 g, 214.29 mmol) in DMF (400 mL), were added 2-(benzyloxycarbonyl)-2-methylpropanoic acid (55.8 g, 236.4 mmol) and potassium carbonate (35.4 g, 256.5 mmol). The resulting solution was stirred for 4 h at room temperature. The resulting solution was diluted with 1000 mL of water. The resulting solution was extracted with ethyl acetate (2×800 mL) and the combined organic layer was washed with water (2×800 mL), brine (1×800 mL). The resulting mixture was concentrated under vacuum. This resulted in 67 g (84%) of Compound 35-1 as a white solid.




To a solution of Compound 35-1 (70 g, 187.7 mmol) in toluene (700 mL), was added NH4OAc (144.5 g, 1.88 mol). The resulting solution was heated to reflux for 3 h in an oil bath. The resulting mixture was concentrated under vacuum. The residue was dissolved in 800 mL of water. The resulting solution was extracted with ethyl acetate (2×500 mL) and the combined organic layer was washed with water (2×800 mL) and brine (1×800 mL). The resulting mixture was concentrated under vacuum. This resulted in 58 g (88%) of Compound 35-2 as a white solid.




To a solution of Compound 35-2 (58 g, 164.3 mmol) in DMF (400 mL), were added cesium carbonate (134 g, 411.0 mmol). This was followed by the addition of ethyl 2-bromoacetate (33 g, 197.6 mmol) dropwise with stirring at room temperature in 30 min. The resulting solution was stirred for 2 h at room temperature. The resulting solution was diluted with 1000 mL of water/ice. The resulting solution was extracted with ethyl acetate (2×700 mL) and the combined organic layer was washed with water (2×800 mL) and brine (1×800 mL). The resulting mixture was concentrated under vacuum. This resulted in 60 g (83%) of Compound 35-3 as a yellow solid.




To a solution of Compound 35-3 (70 g, 159.4 mmol) in methanol (800 mL), was added 10% Pd/C (10 g). The resulting solution was degassed and back filled with hydrogen. The solution was stirred for 3 days at 35° C. The solids were filtered out. The filtrate was concentrated under reduced pressure. This resulted in Compound 35-4 as a white solid: 1H NMR: (DMSO, 300 MHz): δ 7.79-7.74 (m, 2H), 7.13-7.07 (m, 3H), 6.35 (s, 2H), 4.73 (s, 2H), 1.79 (s, 6H)




To a stirred solution of Compound 40-4 (15 g, 57.9 mmol) in THF (300 mL) was added of BH3 Me2S complex (144.2 mL, 2M) dropwise at room temperature in 30 min. The resulting solution was reflux for 4 h. After cooling to room temperature, the resulting solution was diluted with 100 mL of methanol. The pH was adjusted to 1-2 with hydrochloric acid (12N). The mixture was reflux for 1 h. The resulting mixture was concentrated under vacuum. The residue was dissolved in 100 mL of water. pH was adjusted to 9-10 with aqueous potassium carbonate (40%). The resulting solution was extracted with 3×200 mL of DCM and the organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in Compound 35-5 as a white solid.




To a stirred solution of Compound 35-5 (7.3 g, 29.8 mmol) in DMF (150 mL) was added N-Boc-glycine (17 g, 89.4 mmol), followed by HATU (37.2 g, 122 mmol) & DIEA (25.3 g, 178 mmol). The resulting solution was stirred for 3 h at room temperature. The resulting mixture diluted with 600 mL of ethyl acetate, washed with saturated aqueous NaHCO3 (30 mL×6), brine (30 mL×3), dried over anhydrous Na2SO4 and concentrated in vacuo. This resulted in crude product, which was triturated and sonicated with ether (20 mL×3) to give Compound 35-6: 1H NMR (300 MHz, DMSO-d6,) δ7.77-7.72 (m, 2H), 7.54 (s, 1H), 7.20-7.14 (m, 2H), 6.84-6.80 (m, 1H), 4.07 (s, 2H), 3.90 (d, J=3 Hz, 2H), 3.70 (s, 2H), 1.80 (s, 6H), 1.40 (s, 9H).




To a stirred solution of Compound 35-6 (3.02 g, 7.51 mmol) in 30 mL of DCM was added Br2 (0.43 mL, 8.26 mmol) in 3 mL of acetic acid. The reaction mixture was stirred at room temperature for 30 mins. HPLC/MS test showed that desired product (II) was the only peak. Solvent was removed via rotavap at a temperature no higher than 20° C. After neutralization, 3.76 g white solid was obtained. The product was confirmed by 400 MHz proton NMR to be the title compound. The product was used in the next step without further purifications.
Reference Compound 36 was prepared by a similar way that Reference Compound 35 was made except that N-Cbz-glycine was used in step (f). Reference Compound 37 was prepared by a three component Ugi reaction among 2-aminopyrazine, 4-fluorobenzaldehyde, and 2-isocyano-2-methylpropane followed by a HATU mediated amidation reaction with 2-(benzyloxycarbonylamino)-2-methylpropanoic acid and a HCl mediated deprotection. Reference Compound 38 was prepared in the same way that Reference Compound 19, by a three component Ugi reaction among 2-aminopyrazine, 4-fluoro-3-methylbenzaldehyde, and 2-isocyano-2-methylpropane followed by a TFA mediated deprotection. Similarly, Reference Compound 39 was prepared from Reference Compound 19 by a three component Ugi reaction among 2-aminopyrazine, 3-chloro-4-fluorobenzaldehyde, and 2-isocyano-2-methylpropane followed by a TFA mediated deprotection. Reference Compound 40 was prepared by the same way that Reference Compound 19 was prepared: a three component Ugi reaction among 2-aminopyrazine, 4-chloro-3-fluorobenzaldehyde, and 2-isocyano-2-methylpropane followed by a TFA mediated deprotection.
Reference Compound 41
2-(4-fluorophenyl)-6,6,7-trimethyl-5,6,7,8-tetrahydro imidazo[1,2-a]pyrazine




Reference Compound 41 was prepared from Compound 42-2 by the following way:




To a stirred solution of Compound 42-2 (500 mg, 2.04 mmol, 1.00 equiv) in CH3CN (10 mL) was added formalin (5 mL). The reaction mixture was stirred at RT for 20 min, which were followed by addition of NaBH3CN (400 mg, 6.35 mmol, 3.00 equiv) and acetic acid (1 mL, 1.00 equiv). The reaction mixture was allowed to stir for an additional 1 h at room temperature. Sodium hydroxide ON aqueous) was added to neutralize the mixture. The solution was extracted with ethyl acetate (3×10 ml) and the combined organic layer was washed with brine (3×10 mL), dried over anhydrous sodium sulfate. The mixture was concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (40:1). This resulted in the title compound as a light-yellow solid.
Reference Compound 42
tert-butyl 2-(3-bromo-2-(4-fluorophenyl)-6,6-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-oxoethylcarbamate




Reference Compound 42 was prepared from Compound 51-2 by the following way:




To a stirred solution of Compound 51-2 (1.1 g, 3.38 mmol, 1.00 equiv) in DMF (30 mL) was added 3-chloro-2-methylprop-1-ene (500 mg, 5.49 mmol, 1.50 equiv), potassium carbonate (560 mg, 4.06 mmol, 1.10 equiv) and KI (1.12 g, 6.75 mmol, 2.00 equiv) at room temperature. The reaction mixture was stirred for 48 h at 40° C. The reaction mixture was diluted with 100 ml of ethyl acetate. The mixture was washed with brine (3×10 mL), dried over sodium sulfate, concentrated under vacuum. The residue was applied onto a silica gel column with Petroleum Ether/EtOAc (5:1) to give Compound 42-1 as a light yellow solid.




Into a 30-mL sealed tube, was placed Compound 42-1 (2.0 g, 5.28 mmol, 1.00 equiv), AcOH (12 mL), MsOH (2 mL). The reaction mixture was stirred for 12 h at 260° C. (the temperature of the sand bath). The reaction mixture was cooled to room temperature. The mixture was poured into 20 ml of water. The aqueous layer was washed with ethyl acetate (3×10 mL). Aqueous sodium hydroxide (1N) was added to adjust pH to 8. The aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (3×10 ml), dried over sodium sulfate, concentrated under vacuum. The solid was collected by filtration and washed with 5 mL of n-hexane to give Compound 42-2 as a white solid.




To a stirred solution of Compound 42-2 (280 mg, 1.14 mmol, 1.00 equiv) in DMF (10 mL) was added 2-(tert-butoxycarbonyl)acetic acid (600 mg, 3.43 mmol, 3.00 equiv), HATU (1.3 g, 3.42 mmol, 3.00 equiv) and DIEA (880 mg, 6.82 mmol, 6.00 equiv) at room temperature. The reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with 100 ml of ethyl acetate. The organic layer was washed with brine (3×10 mL), dried over sodium sulfate, concentrated under vacuum. The residue was applied onto a silica gel column with DCM/MeOH (10:1) to give Compound 42-3 as a brown solid: 1H NMR: (300 MHz, CDCl3) δ 7.72-7.68 (m, 2H), 7.23 (s, 1H), 7.13-7.07 (m, 2H), 5.46 (s, 1H), 4.65 (s, 2H), 4.05-4.04 (m, 2H), 3.97 (s, 2H), 1.55-1.39 (m, 15H).




To a stirred solution of Compound 42-3 (386 g, 0.96 mmol) in 6 mL of DCM was added Br2 (55 μL, 1.06 mmol) in 2 mL of acetic acid. The reaction mixture was stirred at room temperature for 30 mins. Solvent was removed via rotavap at a temperature no higher than 20° C. After neutralization, the residue was subjected to flash chromatography (40 g, 0-100% ethyl acetate in hexane, 50 mins, dry loading) purification to give the title compound as a colorless oil.
Reference Compound 43
3-bromo-2-(3-fluorophenyl)-7-(4-methoxybenzyl)-5,5-dimethyl-5,6,7,8-tetra hydroimidazo[1,2-a]pyrazine




Reference Compound 43 was prepared from Compound 51-2 by the following way:




To a solution of Compound 43-1 (231 mg, 1.0 mmol) in 10 mL of DMF were added KOH (168 mg, 3.0 mmol), and PMBCl (405 μL, 3.0 mmol) at 0° C. The reaction mixture was stirred at the same temperature for 2 hours and at room temperature for 2 additional hours. The reaction mixture was directly taken to LC/MS purification to give Compound 43-2 as white solid after neutralization.




To a solution of Compound 43-2 (253 mg, 0.72 mmol) in 15 mL of DMF were added 60% NaH (87 mg, 0.085 mmol), and MeI (0.45 mL, 7.2 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with methanol and directly subjected to mass-triggered HPLC purification to give mg of Compound 43-3 as a white solid after neutralization: 1H-NMR: (400 MHz, CDCl3) δ 7.47-7.49 (m, 1H), 7.41-7.45 (m, 1H), 7.28-7.32 (m, 1H), 7.22 (d, J=8.8 Hz, 2H), 6.88-6.93 (m, 1H), 6.86 (d, J=8.8 Hz, 2H), 4.67 (s, 2H), 4.51 (s, 2H), 3.77 (s, 3H), 1.75 (s, 6H).




To a solution of Compound 43-3 (170 mg, 0.45 mmol) in 9 mL of THF was added 1.0 N BH3.THF (2.70 mL, 2.70 mmol) at room temperature. The reaction mixture was stirred at reflux for 2 hours. Pd/C was added (gas generated). The reaction mixture was stirred for 1 hour. Solid was filtered off and solvent was removed. The crude Compound 43-4 was directly tested with 400 MHz proton NMR to prove that the product was the right one. The product was assumed to be of 100% yield and used in the next step without further purifications.




To a stirred solution of Compound 43-4 (164 g, 0.45 mmol) in 6 mL of DCM was added Br2 (26 μL, 0.50 mmol) in 2 mL of acetic acid. The reaction mixture was stirred at room temperature for 30 mins. Solvent was removed via rotavap at a temperature no higher than 20° C. After neutralization, the residue was subjected to ISCO (24 g, 0-100% ethyl acetate in hexane, 25 mins, dry loading) purification to give the title compound as white solid.
Reference Compound 44
tert-butyl 1-(3-bromo-2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydro imidazo[1,2-a]pyrazin-7(8H)-yl)-2-methyl-1-oxopropan-2-ylcarbamate




Reference Compound 44 was prepared from Compound 40-5 by the following way:




To a stirred solution of Compound 35-5 (1.48 g, 6.04 mmol) and NEt3 (6.0 g, 59.4 mmol,) in DCM (20 mL) was added 2-bromo-2-methylpropanoyl bromide (14 g, 60.9 mmol) dropwise at room temperature. After being stirred for 3 h at room temperature, the reaction was then quenched by the addition of 30 mL of water. The resulting solution was extracted with 3×30 mL of ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in crude product as a dark solid, which was washed with EtOAc: Petroleum Ether (1:10) to remove the impurities to produce Compound 44-1 as a gray solid.




To a solution of Compound 44-1 (2.0 g, 5.08 mmol, 1.00 equiv) in DMF (10 mL) was NaN3 (1.0 g, 15.38 mmol, 3.00 equiv) at r.t. The reaction mixture was stirred overnight at room temperature. The resulting solution was diluted with 300 mL of ethyl acetate. The resulting mixture was washed with 3×20 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with Petroleum Ether/EtOAc (5:1) to give Compound 44-2 as a white solid.




To a stirred solution of Compound 44-2 (1.2 g, 3.37 mmol, 1.00 equiv) in methanol (20 mL) was added Pd/C (80 mg, 0.75 mmol, 0.20 equiv) at room temperature. The reaction mixture was evacuated and back filled with H2. The reaction mixture was stirred overnight at room temperature. The solids were filtered out. The resulting mixture was concentrated under vacuum. The solid was washed with Petroleum Ether. This resulted in Compound 44-3 as a white solid.




To a stirred solution of Compound 44-3 (910 mg, 2.76 mmol, 1.00 equiv) in THF (50 mL) was added BOC anhydride (3.2 g, 14.68 mmol, 5.00 equiv), followed by aqueous NaOH (1N, 6 ml, 2.00 equiv) at rt. The resulting solution was stirred for 24 h at 40° C. The resulting solution was concentrated under vacuum. The mixture was diluted with 60 ml of EtOAc. The organic layer was washed with 3×10 ml of brine, dried over Na2SO4, concentrated under vacuum. The solid was collected by filtration and washed with n-hexane (5 ml) to give Compound 44-4 as a white solid: 1H-NMR: (300 MHz, CDCl3) δ 7.75-7.71 (m, 2H), 7.09-7.02 (m, 3H), 4.84 (s, 1H), 4.09-4.0 (m, 4H), 1.98 (s, 6H), 1.55 (s, 6H), 1.45 (s, 9H).




To a stirred solution of Compound 44-4 (32 mg, 0.074 mmol) in 3 mL of DCM was added Br2 (4.2 μL, 0.082 mmol) in 1 mL of acetic acid. The reaction mixture was stirred at room temperature for 30 mins. Solvent was removed via rotavap at a temperature no higher than 20° C. After neutralization, the residue was subjected to flash chromatography (4 g, 0-60% ethyl acetate in hexane, 16 mins) purification to give the title compound as colorless oil.
Reference Compound 45
2-(3-fluorophenyl)-5,5-dimethyl-N-p-tolyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-amine




Reference Compound 45 was prepared from Reference Compound 43 in the following way: To a solution of Reference Compound 43 (116 mg, 0.26 mmol) in 8 mL of dioxane were added 4-methylaniline (84 mg, 0.78 mmol), Pd2(dba)3 (24 mg, 0.026 mmol), XantPhos (30 mg, 0.052 mmol) and Cs2CO3 (169 mg, 0.52 mmol) at room temperature. The reaction mixture was degassed and stirred at 150° C. under N2 for 6 hours. Solid was filtered off and solvent was removed. The residue was subjected to mass-triggered HPLC purification to give 116 mg yellow solid as TFA salt. A solution of the adduct (108 mg, 0.23 mmol) in 2 mL of TFA was stirred at 70° C. for 90 mins in a microwave oven. HPLC test showed that the starting material was gone and the desired product was the major peak. TFA was removed and the residue was directly subjected to flash chromatography purification (12 g, 0-10% methanol in DCM with NH3 modification, 30 mins) to give the title compound as clear oil.
Reference Compound 46 was prepared from Compound 43-4 by a TFA mediated deprotection followed by alkylation. Reference Compound 47 was prepared in the same way that Compound 48-3 was made followed by bromination (except that Reference Compound 51 was used in step (a)).
Reference Compound 48
2-(4-fluorophenyl)-5,5,7-trimethyl-7,8-dihydroimidazo[1,2-a]pyrazine-6(5H)-one




Reference Compound 48 was prepared from Reference Compound 51 by the following way: To a solution of Reference Compound 51 (694 mg, 3.0 mmol) in 20 mL of DMF were added 60% NaH (600 mg, 15 mmol), and MeI (1.87 mL, 30 mmol) at 0° C. The reaction mixture was stirred at the same temperature for 2 hours and at room temperature for 2 additional hours. The reaction mixture was diluted with ethyl acetate and washed with water. The organic solution was dried and concentrated to give the methylated product white solid after flash chromatography purification: 1H NMR: (400 MHz, CDCl3) δ 7.65-7.69 (m, 2H), 7.14 (s, 1H) 7.03 (t, J=8.8 Hz, 2H), 4.62 (s, 2H), 3.11 (s, 3H), 1.70 (m, 6H).
To a stirred solution of (I) (216 mg, 0.79 mmol) in 6 mL of DCM was added Br2 (45 μL, 0.87 mmol) in 2 mL of acetic acid. The reaction mixture was stirred at room temperature for 30 mins. Solvent was removed via rotavap at a temperature no higher than 20° C. After neutralization, the residue was used in the next step without further purifications.
Reference Compound 49
tert-butyl 2-(3-bromo-2-(3-fluorophenyl)-5,5-dimethyl-5,6-dihydro imidazo[1,2-a]pyrazin-7(8H)-yl)-2-oxoethylcarbamate




Reference Compound 49 was prepared from Compound 43-4 by the following way:




A solution of (I) (365 mg, 1.0 mmol) in 10 mL of TFA was stirred at 70° C. for 20 mins HPLC test showed that the starting material was remaining and small amount desired product was detected. The reaction mixture was stirred at 75° C. for 30 mins in a microwave oven. TFA was removed and the residue neutralized to give about 252 mg of Compound 49-1 (100%) as yellow oil.




To a stirred solution of Compound 49-1 (245 mg, 1.0 mmol) and N-Boc-glycine (350 mg, 2.0 mmol) in 10 mL of DMF were added HATU (760 mg, 2.0 mmol) and DIEA (0.52 mL, 3.0 mmol). The reaction mixture was stirred at room temperature for 3 hours
The reaction mixture diluted with ethyl acetate and washed with water. The organic solution was dried and concentrated. The residue was subjected to flash chromatography purification (24 g, 0-100% ethyl acetate in hexane, 36 mins) to give Compound 49-2 as clear oil.




To a stirred solution of Compound 49-2 (312 mg, 0.78 mmol) in 6 mL of DCM was added Br2 (57 μL, 1.1 mmol) in 2 mL of acetic acid. The reaction mixture was stirred at room temperature for 30 mins. Solvent was removed via rotavap at a temperature no higher than 20° C. After neutralization, the residue was subjected to flash chromatography (25 g, 0-100% ethyl acetate in hexane, 32 mins, dry loading) purification to give the title compound as colorless oil.
Reference Compound 50
3-bromo-2-(4-fluorophenyl)-7,8,8-trimethyl-5,6,7,8-tetrahydro imidazo[1,2-a]pyrazine




Reference Compound 50 was prepared from Compound 35-5 by the following way:




To a stirred solution of Compound 35-5 (2.4 g, 9.80 mmol, 1.00 equiv) in CH3CN (50 ml) was added formalin (1.71 g, 21.09 mmol, 2.00 equiv, 37%). The mixture was stirred at 30° C. for 30 minutes. To this was added NaCNBH3 (1.85 g, 29.37 mmol, 3.00 equiv), acetic acid (590 mg, 9.83 mmol, 1.00 equiv). The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 10 ml of water. The pH value of the solution was adjusted to 8-9 with sodium carbonate (saturated). The resulting solution was extracted with DCM (3×100 ml) and the combined organic layer was dried over anhydrous sodium sulfate, concentrated. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:7) to give Compound 50-1 as a white solid: 1H NMR: (300 MHz, CDCl3) δ 7.69-7.75 (m, 2H), 7.02-7.09 (t, J=9 Hz, 2H), 6.97 (s, 1H), 4.01-4.06 (t, J=5.4 Hz, 2H), 3.02-3.07 (t, J=5.4 Hz, 2H), 2.49 (s, 3H), 1.52-1.57 (m, 6H).




To a stirred solution of Compound 50-1 (933 mg, 3.60 mmol) in 6 mL of DCM was added Br2 (204 μL, 3.96 mmol) in 2 mL of acetic acid. The reaction mixture was stirred at room temperature for 30 mins. Solvent was removed via rotavap at a temperature no higher than 20° C. After neutralization, the residue was subjected to flash chromatography (40 g, 0-10% methanol in DCM, 50 mins, dry loading) purification to give 998 mg (82%) of the title compound as white solid.
Reference Compound 51
2-(4-fluorophenyl)-7,8-dihydroimidazo[1,2-a]pyrazin-6(5H)-one




Reference Compound 51 was prepared by the following way:




To a stirred solution of 2-bromo-1-(4-fluorophenyl)ethanone (3.0 g, 13.82 mmol) in DMF (30 mL) was added 2-(tert-butoxycarbonyl)acetic acid (2.5 g, 14.29 mmol) and Cs2CO3 (5.0 g, 15.34 mmol). The resulting solution was allowed to stir overnight at 30° C. The resulting solution was poured into 40 ml of water. The aqueous layer was extracted with ethyl acetate (3×20 mL) and the combined organic layer was washed with brine (3×20 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The solid was washed with a mixture of n-hexane/ethyl acetate (10:1). This resulted in Compound 51-1 as a white solid.




To a stirred solution of Compound 51-1 (25.95 g, 75.14 mmol) in toluene (200 mL), was added NH4OAc (110 g, 20.00 equiv). The resulting solution was heated to reflux for 4 h. The mixture was cooled to room temperature and concentrated under vacuum. The residue was diluted with 800 mL of ethyl acetate. The resulting mixture was washed with brine (3×30 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was washed with 10 mL of Petroleum Ether/EtOAc (20:1) to give Compound 51-2 as a white solid.




To a stirred solution of Compound 51-2 (2.58 g, 8.87 mmol) in DMF (30 mL) was added ethyl 2-bromoacetate (4.4 g, 26.35 mmol, 3.00 equiv) and Cs2CO3 (8.7 g, 26.69 mmol, 3.00 equiv). The resulting solution was stirred overnight at 30° C. The resulting solution was diluted with 30 mL of ethyl acetate and the combined organic layer was washed with brine (3×20 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in Compound 51-3 as a light white solid.




To a stirred solution of Compound 51-3 (8 g, 19.46 mmol) in methanol (200 mL), was added Pd/C (0.8 g). The resulting solution was degassed and back filled with hydrogen. The mixture was stirred overnight at room temperature. The solids were filtered out. The resulting mixture was concentrated under vacuum. The resulting crude solid was washed with 100 mL of Petroleum Ether/EtOAc (1:10). This resulted in the title compound as a white solid.
Reference Compound 52 was prepared from Reference Compound 51 by nitrating with fuming nitric acid in TFA. Reference Compound 53 was prepared in the same way that Reference Compound 19 was prepared: a three component Ugi reaction among 2-aminopyrazine, isonicotinaldehyde, and 2-isocyano-2-methylpropane followed by a TFA mediated deprotection. The free amine was subjected to Pd2(dba)3 mediated amination reaction with 1-bromo-4-methylbenzene followed by a PtO2 mediated hydrogenation. Reference Compound 54 was prepared from 2-aminopyrazine, 2-methoxybenzaldehyde, 1-isocyano-4-methylbenzene by the same three component Ugi reaction to prepare Reference Compound 1, and then followed by a PtO2 mediated hydrogenation.
Reference Compound 55
3-bromo-2-(4-fluorophenyl)-8,8-dimethyl-7,8-dihydroimidazo[1,2-a]pyrazin-6(5H)-one




Reference Compound 55 was prepared from Compound 35-4 in the following way: To a stirred solution of Compound 35-4 (390 mg, 1.51 mmol, 1.00 equiv) in DCM (20 mL) was added NBS (0.28 g, 1.00 equiv). The resulting solution was stirred for 2 hours at room temperature. The solid was filtered out and the mixture was washed with a saturated solution of Na2S2O3, dried over Na2SO4. The mixture was concentrated under vacuum. The solids was purified by silica gel chromatography (Petroleum Ether/EtOAc=1:2) to result in the title compound as a white solid.
Reference Compound 56 was prepared from Compound 35-5 by reacting with Boc-OSu in THF at 50° C. Reference Compound 57 was prepared from Compound 35-4 by alkylation using NaH/MeI. Reference Compound 58 was prepared by the same way that Compound 35-4 except that (R)-2-(benzyloxycarbonyl)-3-methylbutanoic acid was used in step (a). Reference Compound 59 was prepared in the same way that compound 35-4 except that 2-bromo-1-(3,4-difluorophenyl)ethanone was used in step (a). Reference Compound 60 was prepared by the same way that Compound 35-4 was made except that (S)-2-(benzyloxycarbonyl)propanoic acid was used in step (a). Reference Compound 61 was prepared by the same way that Compound 35-4 was made except that (S)-2-(benzyloxycarbonyl) 3-methylbutanoic acid was used in step (a). Reference Compound 62 was prepared by the same way that Compound 35-4 was made except that (R)-2-(benzyloxycarbonyl)propanoic acid was used in step (a). Reference Compound 63 was prepared from by the same method that Reference Compound 35 was prepared except that (S)-2-(benzyloxycarbonyl)-3-methylbutanoic acid was used in step (a). Reference Compound 64 was prepared from by the same method that Reference Compound 35 was prepared except that (R)-2-(benzyloxycarbonyl)-3-methylbutanoic acid was used in step (a). Reference Compound 65 was prepared from by the same method that Reference Compound 35 was prepared except that (S)-2-(benzyloxycarbonyl)-3-methylbutanoic acid was used in step (a). Reference Compound 66 was prepared from by the same method that Reference Compound 35 was prepared except that (R)-2-(benzyloxycarbonyl)-3-methylbutanoic acid was used in step (a). Reference Compound 67 was prepared in the same way that Reference Compound 55 was made except that 2-bromo-1-(3-fluorophenyl)ethanone was used in step (a). Reference Compound 68 was prepared from Reference Compound 19 by an amination reaction with 1-bromo-2,4-difluorobenzene followed by a Pd/C mediated hydrogenation. Reference Compound 69 was synthesized from Reference Compound 32 was prepared from an amination reaction with 1-bromo-3-fluoro-4-chlorobenzene followed by a PtO2 mediated hydrogenation. Reference Compound 70 was synthesized from Reference Compound 11 was prepared from an amination reaction with 1-bromo-3-fluoro-4-chlorobenzene followed by a PtO2 mediated hydrogenation. Reference Compound 71 was synthesized from Reference Compound 51 in a similar way as Reference Compound 49 was prepared.
Reference Compound 72
3-bromo-7-(2-(dimethylamino)ethyl)-2-(4-fluorophenyl)-8,8-dimethyl-7,8-dihydroimidazo[1,2-a]pyrazin-6(5H)-one




Reference Compound 72 was prepared from Compound 35-4 by the following reaction:




To a solution of Compound 35-4 (259 mg, 1.0 mmol) in 5 mL of DMF were added 60% NaH (60 mg, 1.5 mmol, and 2-bromo-N,N-dimethylethanamine (228 mg, 1.5 mmol) at room temperature. The reaction mixture was stirred at room temperature for 6 hours. LC/MS test showed that Compound 35-4 was gone and the desired product ([M+1]=331 was one the major peaks.
The reaction mixture was diluted with ethyl acetate and washed with water twice. The organic solution was dried and concentrated. The obtained crude product was used in the next step without further purifications.
To a stirred solution of crude product obtained from the previous step (198 mg, 0.60 mmol) in 3 mL of DCM was added Br2 (34 μL, 0.66 mmol) in 1 mL of acetic acid. The reaction mixture was stirred at room temperature for 30 minutes. HPLC/MS test showed that starting material gone and Reference Compound 72 was the major product.
Solvent was removed via rotavap at a temperature no higher than 20° C. The residue was subjected to a mass-triggered HPLC purification to give 110 mg of Reference Compound 72.
Reference Compound 73: 3-(4-fluoro-3-methylphenylamino)-2-(3-fluorophenyl)-8,8-dimethyl-7,8-dihydroimidazo[1,2-a]pyrazin-6 (5H)-one was synthesized from Reference Compound 67 by a Pd2(dba)3 mediated amination reaction with 4-fluoro-3-methylaniline. Reference Compound 74: tert-butyl 3-bromo-2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydro imidazo[1,2-a]pyrazine-7(8H)-carboxylate was prepared from Reference Compound 56 by a bromination reaction with Br2. Reference Compound 75: 2-bromo-1-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone was prepared from Example 493 by an amidate reaction with 2-bromoacetyl bromide.
Reference Compound 76
2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-amine




Reference Compound 76 was prepared by the following steps:




To a stirred solution of 5-methylpyridin-2-amine (260 mg, 2.4 mmol) in 20 mL of MeOH was added 4-fluorobenzaldehyde (0.26 mL, 2.40 mmol), and followed by 1.0 N HClO4 in MeOH (0.20 mL, 0.20 mmol). The reaction mixture was stirred at room temperature for 0.5 hour which was followed by addition of 2-isocyano-2-methylpropane (0.23 mL, 2.0 mmol). The stirring was continued at room temperature overnight. HPLC/MS test showed that the desired product Reference Compound 76-1 was a major peak.
The reaction mixture was subjected to direct mass-triggered HPLC purification. The obtained 62 mg of the Ugi adduct as yellow solid.




To a solution of the Ugi adduct (366 mg, 1.23 mmol) in 5 mL of DCM was added 5 mL of TFA. The reaction mixture was stirred at room temperature. LC/MS test showed a major peak with [M+1]=338, which corresponded to Reference Compound 76-2. The reaction mixture was concentrated to give 431 mg yellow solid.
To a solution of Reference Compound 76-2 (101 mg, 0.30 mmol) in 3 mL of MeOH and 3 mL of water was added KOH (168 mg, 3.0 mmol). The reaction mixture was stirred at 60° C. for 3 hours. LC/MS test showed a major peak with [M+1]=242, which corresponded to the desired product of Reference Compound 76. The reaction mixture was concentrated and the residue was dissolved in DCM. The organic solution is washed with NaHCO3, dried and concentrated. The product was used without further purifications.
Reference Compound 77: 2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-amine was prepared by the same steps as Reference Compound 76.














Physical Data


Compound
Structure
MS (m/z) and/or 1H NMR







Ref. comp. 71




[M + 1] = 481 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J = 7.2 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 4.67- 4.82 (m, 2H), 4.05 (s, 2H), 3.55-3.78 (m, 2H), 1.71 (s, 3H), 1.67 (s, 3H), 1.41 (s, 9H)


 


Ref. comp. 72




[M + 1] = 409 1H NMR (400 MHz, CD3OD): δ 7.61-7.65 (m, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.23-7.26 (m, 2H), 7.08 (d, J = 8.4 Hz, 2H), 4.26 (s, 2H), 4.15 (s, 2H), 4.11 (s, 2H), 3.88 (s, 2H), 2.08 (s, 6H)


 


Ref. comp. 73




[M + 1] = 383


 


Ref. comp. 74




[M + 1] = 424 1H NMR (400 MHz, CDCl3): δ 7.87-7.90 (m, 2H), 7.08 (t, J = 8.8 Hz, 2H), 3.88-3.94 (m, 4H), 1.85 (s, 6H), 1.53 (s, 9H)


 


Ref. comp. 75




[M + 1] = 475


 


Ref. comp. 76




[M + 1] = 242


 


Ref. comp. 77




[M + 1] = 228 1H NMR (400 MHz, CDCl3): δ 7.94-7.80 (m, 3H), 7.52 (dt, J = 1.2, 9.2 Hz, 1H), 7.10-7.15 (m, 3H), 6.81 (dt, J = 1.2, 6.8 Hz, 1H), 3.33 (br, 2H)









Example 1
2-amino-1-(3-(benzo[d][1,3]dioxol-5-ylamino)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone




Example 1 was prepared in the following way: to a stirred solution of N—BOC-glycine (142 mg, 0.81 mmol) in 2 mL of DMF were added HATU (308 mg, 0.81 mmol) and DIEA (0.28 mL, 1.62 mmol). After stirring for 10 minutes, Reference Compound 1 (180 mg, 0.54 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours.
Solvent was removed and the crude product was subjected to MS-triggered HPLC purification. The collected MeCN/water solution was concentrated till no more MeCN was left. The remaining aqueous solution was neutralized with NaHCO3 and extracted with DCM. The organic solution was dried and concentrated. The residue was dissolved in 1:1 MeCN/water solvent, dried on a lyophilizer to give 192 mg powdery product.
A solution of the above obtained amide (265 mg, 0.54 mmol) in 10 mL of 4:1 DCM and TFA was stirred at room temperature for 2 hours. Solvent was removed and the crude product was subjected to MS-triggered HPLC purification. The collected MeCN/water solution was concentrated till no more MeCN was left. The remaining aqueous solution was neutralized with NaHCO3 and extracted with DCM. The organic solution was dried and concentrated. Then was dissolved in 1:1 MeCN/water solvent, dried on lyophilizer to give powdery product.
Example 26
N,2-bis(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine




Example 26 was synthesized by the following way: to a stirred solution of 2-aminopyrazine (683 mg, 7.18 mmol) in 50 mL of MeOH were added 4-fluorobenzaldehyde (1.16 mL, 10.8 mmol), 1-fluoro-4-isocyanobenzene (1.0 g, 8.25 mmol), and followed by 1.0 N HClO4 in MeOH (0.72 mL, 0.72 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was subjected to flash chromatography purification. The collected organic solution was concentrated to give the title compound as yellow oil.
Example 28
N,2-bis(4-fluorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-amine




Example 28 was synthesized by the following way: to a stirred solution of Example 26 (761 mg, 2.36 mmol) in 10 mL of MeOH was added Pd/C (258 mg, 0.24 mmol). The reaction mixture was evacuated and back filled with H2. The reaction mixture was stirred at room temperature overnight. The solid was filtered off and solvent was removed. The product was subjected to mass-triggered HPLC purification. The obtained MeCN/water solution was combined and concentrated to give the final product as yellow oil after neutralization.
Example 29
2-amino-1-(3-(3,4-difluorophenylamino)-2-(4-fluorophenyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-methylpropan-1-one




Example 29 was synthesized by the following way: To a stirred solution of 2-(tert-butoxycarbonylamino)-2-methylpropanoic acid (25 mg, 0.12 mmol) in 2 mL of DMF were added HATU (46 mg, 0.12 mmol) and DIEA (63 μL, 0.36 mmol). After stirring for 10 minutes, Example 331 (21 mg, 0.06 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was directly subjected to a mass-triggered HPLC purification. The collected MeCN/water solution was concentrated and neutralized. The obtained product (26 mg, 0.05 mmol) in 5 mL of 4:1 DCM and TFA was stirred at room temperature for 2 hours. The reaction mixture was concentrated and the residue was subjected to mass-trigger HPLC purification. The collected MeCN/water solution was combined and MeCN was removed.
Example 32
1-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-(methylamino)ethanone




Example 32 was prepared from Example 28 by the following way:




Example 28 (33 mg, 0.10 mmol) in 10 mL of DCM were added Et3N (84 μL, 0.60 mmol) and 2-chloroacetyl chloride (24 μL, 0.30 mmol) at 0° C. The reaction mixture was stirred at the same temperature for 2 hours and at room temperature for 2 additional hours. Solvent was removed and the residue was subjected to MS-triggered HPLC purification to give 40 mg of Compound 32-1 as yellow solid (100%) after neutralization: 1H NMR (CDCl3, 400 MHz) δ 7.63-7.66 (m, 2H), 6.99 (t, J=8.8 Hz, 2H), 6.90 (t, J=8.4 Hz, 2H), 6.60-6.63 (m, 2H), 4.97-5.14 (m, 2H), 4.13-4.21 (m, 2H), 4.03 (d, J=3.2 Hz, 2H), 3.91 (s, 2H).




Compound 32-1 (20 mg, 0.05 mmol) in 5 mL of DMF were added K2CO3 (21 mg, 0.15 mmol) and 2.0 M MeNH2 (0.30 mL, 0.60 mmol) at room temperature. The reaction mixture was stirred at the same temperature overnight. Solvent was removed and the residue was subjected to MS-triggered HPLC purification to give the title compound as yellow solid after neutralization.
Example 44
1-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-hydroxyethanone




Example 44 was synthesized by the following way: to a solution of Compound 32-1 (20 mg, 0.05 mmol) in 5 mL of DMF were added KI (8 mg, 0.05 mmol) and AcOK (15 mg, 0.15 mmol) at room temperature. The reaction mixture was stirred at the same temperature overnight. Solvent was removed and the residue was subjected to MS-triggered HPLC purification to give yellow solid. A solution of the solid (21 mg, 0.05 mmol) in 3 mL of methanol and 1 mL of water was added LiOH (6 mg, 0.25 mmol). The reaction mixture was stirred at 40° C. for 2 hours. The reaction mixture was cooled to room temperature and organic solvent was removed. The residue was taken to mass triggered HPLC separation. The collected MeCN/water solution was concentrated to give the title compound as yellowish oil.
Example 113
2-(4-fluorophenyl)-N-p-tolyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-amine




Example 113 was prepared by the following way: to a stirred solution of the Example 136 (64 mg, 0.20 mmol) in 5 mL of MeOH was added Pd/C (21 mg, 0.02 mmol). The reaction mixture was evacuated and back filled with H2. The reaction mixture was stirred at room temperature overnight. The solid was filtered off and solvent was removed. The residue was subjected to mass-triggered HPLC purification to give a yellow solid.
Example 136
2-(4-fluorophenyl)-N-p-tolylimidazo[1,2-a]pyrazin-3-amine




Example 136 was prepared by the following way: to a solution of Reference Compound 19 (69 mg, 0.30 mmol) in 6 mL of dioxane were added 4-bromotoluene (74 μL, 0.60 mmol), Pd2(dba)3 (8 mg, 0.009 mmol), Xantphos (11 mg, 0.018 mmol) and Cs2CO3 (196 mg, 0.60 mmol) at room temperature. The reaction mixture was degassed and stirred at 120° C. under N2 for 5 hours. The reaction mixture was cooled to room temperature and solid was filtered off. The resulting filtrate was concentrated. The residue was subjected to mass-triggered HPLC purification to give about 72 mg of the title compound as yellow oil (75%) after neutralization.
Example 251
(3-(dimethylamino)pyrrolidin-1-yl)(2-(4-fluorophenyl)-3-(p-tolylamino)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)methanone




Example 251 was prepared from Example 113 by the following way:




To a stirred solution of Example 113 (161 mg, 0.50 mmol) and Et3N (139 μL, 1.5 mmol) in 10 mL of DCM were added 4-nitrophenyl carbonochloridate (202 mg, 1.0 mmol). The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was subjected to MS-triggered HPLC separation. The collected MeCN/water solution was combined and concentrated to give Compound 251-1 as yellow oil: 1H NMR: (300 MHz, DMSO-d6) δ8.34-8.31 (m, 3H) 7.80-7.75 (m, 2H) 7.54 (m, 2H) 7.35-7.29 (m, 1H) 7.20-7.14 (m, 2H) 6.60-6.50 (m, 2H) 4.93 (s, 1H) 4.74 (s, 1H) 4.07 (s, 1H) 3.92 (s, 1H) 3.81 (m, 2H).




Compound 251-1 (20 mg, 0.041 mmol) and Et3N (17 μL, 0.123 mmol) in 2 mL of NMP were added N,N-dimethylpyrrolidin-3-amine (15 μL, 0.123 mmol). The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was subjected to MS-triggered HPLC purification. The collected MeCN/water solution was combined and concentrated to give the title compound as yellow oil.
Example 262
N-(4-chlorophenyl)-2-(4-fluorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-mine




Example 262: was prepared by the following way: to a solution of Reference Compound 19 (69 mg, 0.30 mmol) in 6 mL of dioxane were added 1-bromo-4-chlorobenzene (115 mg, 0.60 mmol), Pd2(dba)3 (8 mg, 0.009 mmol), Xantphos (11 mg, 0.018 mmol) and Cs2CO3 (196 mg, 0.60 mmol) at room temperature. The reaction mixture was degassed and stirred at 120° C. under N2 for 5 hours. The reaction mixture was cooled to room temperature and solid was filtered off. The resulting filtrate was concentrated. The residue was subjected to mass-triggered HPLC purification to give a yellow oil after neutralization. To a stirred solution of the obtained adduct (68 mg, 0.20 mmol) in 5 mL of MeOH was added Pd/C (21 mg, 0.02 mmol). The reaction mixture was evacuated and back filled with H2. The reaction mixture was stirred at room temperature overnight. The solid was filtered off and solvent was removed. The residue was subjected to mass-triggered HPLC purification to give 39 mg (57%) of the title compound as yellow solid.
Example 266
2-m-tolyl-N-p-tolyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-amine




Example 266 was synthesized by the following way: to a 100-mL round-bottom flask, was placed a solution of pyrazin-2-amine (1.2 g, 12.6 mmol), 3-methylbenzaldehyde (1.44 g, 12.0 mmol) and HClO4 (200 mg, 2.0 mmol) in methanol (10 mL). The reaction mixture was stirred at room temperature for 30 minutes, then to the mixture was added 1-isocyano-4-methylbenzene (1.2 g, 10.3 mmol). The resulting solution was allowed to stir for 12 hr at room temperature. After removing the solvent, the residue was applied onto a silica gel column with dichloromethane/methanol (10:1) to result 1.1 g the Ugi adduct. To a solution of the obtained Ugi adduct (1.0 g, 3.18 mmol) in methanol (50 mL) was added PtO2 (72 mg, 0.32 mmol). Then the reaction mixture was evacuated and back filled with H2. The reaction mixture was stirred at RT overnight. The solid was filtered out and the filtrate was concentrated under vacuum to result in the title compound as a white solid.
Example 267
(S)-tert-butyl 1-(2-(4-fluorophenyl)-3-(p-tolylamino)-5,6-dihydroimidazo[1,2-a]pyrazin-7 (8H)-yl)-1-oxo-3-(4-(pentylamino)phenyl)propan-2-ylcarbamate




Example 267 was synthesized from Example 113 by a HATU mediated coupling with (S)-2-(tert-butoxycarbonylamino)-3-(4-nitrophenyl)propanoic acid followed by Pd/C mediated hydrogenation for the aniline derivative. To a stirred solution of aniline derivative (33 mg, 0.056 mmol) in 5 mL of dry THF was added pentanal (18 μL, 0.168 mmol) under nitrogen at room temperature. NaBH4 (6 mg, 0.168 mmol) was added after 30 mins. The reaction mixture was stirred at room temperature for 3 hours. Solvent was removed. The residue was dissolved in methanol and subjected to mass-triggered HPLC purification. The obtained MeCN/water solution was combined and concentrated to give yellow oil.
Example 289
(5R,8R)-2,8-dibenzyl-3-methyl-5-phenethyl-7,8-dihydroimidazo[1,2-a]pyrazin-6(5H)-one




Example 289 was prepared in the following way:




To a stirred solution of (R)-2-(benzyloxycarbonylamino)-3-phenylpropanoic acid (5 gm, 1.0 eq.) and (R)-ethyl 2-amino-3-phenylpropanoate hydrochloride (3.83 gm, 1.0 eq.) in 30 mL of DMF were added HATU (6.98 gm, 1.1 eq.) and DIEA (3.44 ml, 1.1 eq.). The reaction mixture was stirred at room temperature for 6 hours. HPLC/MS test showed that desired product Compound 289-1 was the only product, but was contaminated with other peak. The reaction was partitioned between EtOAc/water and then crude was purified with flash chromatography to give Compound 289-1.




To a stirred solution of Compound 289-1 (3 gm, 1.0 eq.) and 9.5 ml of 2 N NaOH and 30 ml THF were mixed. The reaction mixture was stirred at room temperature for 6 hours. The reaction was acidified and then partitioned between EtOAc/water and then crude was as such in the next step.




To a stirred solution of Compound 289-2 (1 gm, 1.0 eq.) and acetic anhydride (0.254 ml, 1.2 eq.) in dichloromethane (25 ml) were added DIEA (0.756 ml, 4.4 eq.)) and DMAP (13.4 mg, 5 m %). The reaction mixture was stirred at room temp. for 8 hrs. LCMS indicated that the desired product was formed. The organic layer was quenched with MeOH and concentrated. The organic layer was washed with water/EtOAc and used as crude in next step.




Compound 289-3 (0.8 gm, 1.0 eq.) and (R)-ethyl 2-amino-4-phenylbutanoate (0.596 gm, 1.6 eq.) were mixed along with PTSA (10 m %). The reaction was heated to 130° C. in a Dean-Stark apparatus. Slight vacuum was applied from the top to get vigorous reflux. The reaction was heated for 2 hrs. Toluene was removed from the side arm and the volume was replenished in the main vessel 3-4 times to drive the reaction to completion. LCMS indicated completion of reaction as indicated by formation of new peak. The new peak had no mass. The reaction was concentrated and crude was subjected to next step.




Compound 289-4 was dissolved in pyridine and POCl3 was added the reaction was stirred for 48 hrs. LCMS indicated that desired product was formed. The reaction was concentrated. The oil was neutralized with sat. NaHCO3. and extracted with dichloromethane. The organic layer was dried/concentrated and subjected to column chromatography.




To a stirred solution of Compound 289-5 (0.7 g, 1.0 eq.) in 30 mL of MeOH was added Pd/C (0.007 g). The reaction mixture was evacuated and back filled with H2. The reaction mixture was stirred at room temperature overnight. HPLC test showed that the starting material is all gone and (II) was the major peak. Solid was filtered off and solvent was removed to give the title compound. LCMS indicated that the reaction had racemized (2 peaks).
Example 292
N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-N-methyl-5,6,7,8-tetrahydro imidazo[1,2-a]pyrazin-3-amine




Example 292 was prepared by the following way: to a stirred solution of pyrazin-2-amine (2.4 g, 25.26 mmol) in 20 ml of MeOH, were added 4-fluorobenzaldehyde (3.0 g, 24.19 mmol), and HClO4 (70%, 0.4 g), then the mixture was stirred at room temperature for 30 min which was followed by addition of 1-chloro-2-fluoro-4-isocyanobenzene (3.2 g, 20.58 mmol). The stirring was continued at room temperature overnight, Then the solvent was removed in vacuo, and the crude product was purified by silica gel chromatography with dichloromethane/methanol to yield the Ugi adduct as a yellow solid.
To a solution of the obtained Ugi adduct (1.2 g, 3.36 mmol, 1.00 equiv) in DMF (10 mL) was added sodium hydride (1.0 g, 25.00 mmol, 1.20 equiv, 60%) at 0° C. The reaction mixture was stirred at this temperature for 30 mins, which was followed by addition of iodomethane (1.7 g, 11.97 mmol, 3.56 equiv). The resulting solution was allowed to react, with stirring, for 30 min at 0° C. The reaction mixture was poured into 20 ml of ice water. The solid was collected by filtration and washed with 10 ml of water to result in 1.1 g (88%) of the N-methyl product.
To a solution of the N-methyl product (1.0 g, 2.70 mmol, 1.00 equiv) in methanol (100 mL) was added PtO2 (30 mg, 0.13 mmol, 0.10 equiv). The resulting solution was allowed to react, with stirring, for 8 hr at room temperature. The solids were filtrated out, and the resulting solution was concentrated under vacuum. The residue was applied onto silica gel chromatography with dichloromethane/methanol (20:1) to result in 500 mg (49%) of the title compound as a white solid.
Example 297
N-tert-butyl-2-(4-fluorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-amine




Example 297 was synthesized from the precursor of Reference Compound 19-1 by the following way: to a solution of Reference Compound 19-1 (1.0 g, 3.52 mmol, 1.00 equiv) in methanol (20 mL), was added PtO2 (80 mg, 0.35 mmol, 0.10 equiv). The resulting solution was evacuated and back filled with hydrogen, and the stirring was continued at room temperature overnight. The solid was filtered off and the solvent was evaporated under vacuum. The residue was applied to silica gel chromatography with dichloromethane/methanol (50:1) to give 837 mg (83.7%) of the title compound as a white solid.
Example 412
2-amino-1-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone




Example 412 was prepared from Reference Compound 35 by a Pd2(dba)3 mediated amination reaction with p-toluidine followed by a TFA mediated deprotection.
Synthesis of Reference Compound 35-4:
To a stirred solution of Reference Compound 35-3 (70 g, 159.45 mmol, 1.00 equiv.) in methanol (800 mL) was added Palladium on carbon (10 g). The resulting solution was degassed and back filled with hydrogen. The solution was stirred for 3 days at 25° C. The solids were filtered out and washed with MeOH. The filtrate was concentrated under reduced pressure. This resulted in Reference Compound 35-4 (38 g, 145.56 mmol, 91%) of as a white solid. LC-MS: (ES, m/z): [M+H]+ calculated for C14H14FN3O 260, found 260. H-NMR: (DMSO, 300 Hz) δ 7.79-7.74 (2H, m), 7.13-7.07 (3H, m), 6.35 (H, s), 4.73 (2H, s), 1.79 (6H, s).
Synthesis of Reference Compound 35-5:
Reference Compound 35-4 (5 g, 19.2 mmol, 1 equiv.) was dissolved in 50 mL of THF, 1M Borane/THF complex (57 ml, 57 mmol, 3 equiv.) was added slowly and reaction was refluxed overnight. LCMS indicated that the reaction was complete. THF was removed under reduced pressure. The reaction was quenched with MeOH. The crude product of Reference Compound 35-5 (4.5 g, 18.3 mmol, 95%) was used in the next step. LC-MS: (ES, m/z): [M+H]+ calcd for C14H17FN3 246, found 246. H-NMR: (DMSO, 300 Hz) δ 7.75-7.70 (2H, m), 7.4 (s, 1H), 7.14 (2H, J=9 Hz, t), 3.9 (2H, J=5.4 Hz, t), 2.51 (2H, J=5.4 Hz, t), 1.41 (6H, s).
Synthesis of Reference Compound 35-6:
To a stirred solution of Reference Compound 35-5 (2.9 g, 11.82 mmol, 1.1 equiv.) and 2-(tert-butoxycarbonylamino)acetic acid (2.27 g, 13 mmol, 1.1 equiv.) in 15 mL of dichloromethane were added DIEA (2.47 ml, 14.18 mmol, 1.2 equiv.), HATU (5.39 gm, 14.18 mmol, 1.2 equiv.). The reaction mixture was stirred at room temperature for 8 hours. HPLC/MS analysis showed that desired product Reference Compound 35-6 was the major product. The reaction was diluted 70 ml dichloromethane. The organic layer was washed with washed with water (1×30 ml), followed by saturate NaHCO3 (1×30 ml) and finally with brine (1×30 ml). The organic layer was then dried over anhydrous Na2SO4, and concentrated in vacuo. The resulting oil was purified using column chromatography with hexanes/ethyl acetate (0-100% linear gradient) used as eluant. The desired product Reference Compound 35-6 was obtained as an oil (3.3 g, 8.27 mmol, 70%). 1H NMR: (300 Hz, DMSO-d6,) δ7.77 ̃7.72 (2H, m), 7.54 (1H, s), 7.20 ̃7.14 (2H, m), 6.84 ̃6.80 (1H, m), 4.07 (2H, s), 3.90 (2H, d, J=3 Hz), 3.70 (2H, s), 1.80 (6H, s), 1.40 (9H, s). LC-MS: (ES, m/z): [M+H]+ calcd for C21H28FN4O3 403 found 403.
Synthesis of Reference Compound 36:
To a solution of Reference Compound 35-6 (2.0 g, 4.97 mmol, 1.00 equiv.) in MeCN (20 mL) was added NBS (0.88 g, 1.00 equiv). The resulting solution was stirred for 15 minutes at room temperature. HPLC/MS indicated that the desired product Reference Compound 36 was formed exclusively. The reaction was evaporated under reduced pressure. The solids were dissolved in 50 ml dichloromethane. The organic layer was then dried over anhydrous Na2SO4, and concentrated in vacuo. The resulting solids were purified with column chromatography using hexanes/ethyl acetate (0-100%) as eluant. The desired compound Reference Compound 36 was obtained as an off white/glassy solid (1.9 g, 3.96 mmol, 80%). LC-MS: (ES, m/z): [M+H]+ calcd for C21H27BrFN4O3 482 found 482. H-NMR: (MeOH-d4, 400 Hz) δ 7.84-7.81 (2H, m), 7.14 (2H, J=8.8 Hz, t), 4.09-4.01 (4H, m), 3.81 (2H, J=4.8 Hz, t), 1.89 (6H, s), 1.46 (9H, s).
Synthesis of Example 412
In a glass vial, Cs2CO3, 4F-aniline (0.462 g, 4.1 mmol, 2.0 equiv.), Pd2(dba)3 (0.095 g, 0.104 mmol, 0.05 equiv.), Xantphos (0.120 g, 0.208 mmol, 0.1 equiv.) and dioxane were stirred for 5 minutes at room temperature. Reference Compound 36 (1 g, 2.08 mmol, 1.0 equiv.) was added to the reaction mixture after which the reaction mixture was degassed for 15 mins and then stirred at 120° C. under N2 for 8 hours. HPLC/MS test showed that the starting material Reference Compound 36 was consumed and desired product was formed predominantly along with some Reference Compound 35-6. The reaction was filtered to remove solids. The reaction mixture was concentrated and then purified by normal phase column chromatography (silicagel 80 gm) using a gradient of 100%-0 to 0-100% hexane:EtOAc. The desired product elutes at 60:40 EtOAc:hexanes. The organic layer was concentrated at reduced pressure to yield the Boc derivative (950 mg, 89.3%) yield. LC-MS: (ES, m/z): [M+H]+ calcd for C27H32F2N5O3 512 found 512.
The Boc-compound was treated with 20% TFA in CH2Cl2 (50 ml) was the reaction was stirred for 4 hours) was added to the mixture. After the completion of this reaction (monitored by LCMS), the resulting mixture was concentrated under reduced pressure. The resulting residue was purified by reverse phase HPLC to yield product as a TFA salt. The ACN-water layer was concentrated to remove all the solvents. The residue was dissolved in dichloromethane and carefully neutralized by sat. NaHCO3. The organic layer was successively washed with brine followed by water. The organic layer was concentrated to yield Example 412 (450 mg, 52% for 2 steps). LC-MS: (ES, m/z): [M+H]+ calcd for C22H23F2N5O 412 found 412. H-NMR: (MeOH-d4, 400 Hz) δ 7.61-7.57 (2H, m), 6.94 (2H, J=8.8 Hz, t), 6.81 (2H, J=8.8 Hz, t), 6.47 (2H, m), 3.72 (2H, m), 3.58 (2H, m), 3.42 (2H, m), 1.85 (6H, s). Elemental Analysis: (Example 412 with 0.65 equiv. H2O): C, 62.44; N, 16.55; H, 5.79, (calculated). C=62.54/62.44; N=16.35/16.29; H=5.52/5.61 (experimental).
Example 417
2-amino-1-(3-(4-chlorophenylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone




Example 417 was prepared from Reference Compound 36 by a Pd2(dba)3 mediated amination reaction with 4-chloroaniline followed by a 6N HCl mediated deprotection.
Example 331
N-(3,4-difluorophenyl)-2-(4-fluorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-amine




Example 331 was synthesized from Reference Compound 19 by the following way: to a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of Reference Compound 19 (1.5 g, 6.12 mmol) and 4-bromo-1,2-difluorobenzene (2.4 g, 12.44 mmol) in 1,4-dioxane (100 mL) were added Pd2(dba)3 (170 mg, 0.19 mmol), X-Phos (175 mg, 0.37 mmol) and Cs2CO3 (4 g, 12.28 mmol) under nitrogen. The resulting solution was heated to 120° C. and stirred overnight. The solids were filtrated out and the resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2) to result in 1.9 g (87%) of diaryl amine as a brown solid.
To a solution of the obtained diaryl amine (1.9 g, 5.33 mmol) in methanol (50 mL) was added PtO2 (130 mg, 0.57 mmol). The mixture was degassed and backed filled with hydrogen. The resulting solution was allowed to react, with stirring, overnight at room temperature. The solids were filtrated and the resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with DCM/MeOH (50:1) to result in the title compound as a brown solid.
Example 529
2-amino-1-(2-(4-fluorophenyl)-8,8-dimethyl-3-(p-tolylamino)-5,6-dihydro imidazo[1,2-a]pyrazin-7(8H)-yl)-2-methylpropan-1-one




Example 529 was prepared from Example 415 by the following way:




To a stirred solution of Example 415 (21 mg, 0.06 mmol) and Et3N (83 μL, 0.60 mmol) in 6 mL of dry DCM was added 2-bromo-2-methylpropanoyl bromide (71 μL, 0.60 mmol). The reaction mixture was stirred at room temperature for 5 hour. The reaction mixture was concentrated and subjected to mass-triggered LC/MS purification directly. The obtained solutions were concentrated to give 22 mg (73%) of Compound 529-1 as yellow oil after neutralization.




To a solution of Compound 529-1 (22 mg, 0.044 mmol) in 3 mL of DMF was added NaN3 (8.6 mg, 0.132 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was directly subjected to mass-triggered LC/MS purification directly. The obtained MeCN/aqueous solution was combined and concentrated to give 15 mg (75%) of Compound 529-2 as yellow oil after neutralization.




To a solution of Compound 529-2 (15 mg, 0.033 mmol) in 3 mL of MeOH was added 10% Pd/C (4 mg, 0.003 mmol) at room temperature. Air was removed and H2 was filled. The reaction mixture was stirred at room temperature for 2 hours. Solid was filtered off and solvent was removed. The reaction mixture was directly subjected to mass-triggered HPLC purification to give 15 mg (100%) of the title compound yellow oil.
Example 530
tert-butyl 1-(2-(4-fluorophenyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-methyl-1-oxopropan-2-ylcarbamate




Example 530 was prepared from Compound 540-1 by the following way:




To a stirred solution of Compound 540-1 (1.0 g, 4.61 mmol, 1.00 equiv) in DMF (20 mL) was added 2-(tert-butoxycarbonyl)-2-methylpropanoic acid (1.12 g, 5.52 mmol, 1.20 equiv), EDC (1.06 g, 5.52 mmol, 1.20 equiv), HOBT (1.8 g, 13.24 mmol, 2.87 equiv), DIEA (1.78 g, 13.80 mmol, 2.99 equiv). The resulting solution was stirred overnight at 60° C. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 100 mL of water. The resulting solution was extracted with ethyl acetate (2×150 mL) and the organic combined layer was concentrated. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10 ̃1:2 ̃1). This resulted in the title compound as a yellow solid.
Example 540
tert-butyl 2-(2-(4-fluorophenyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-oxoethylcarbamate




Example 540 was prepared from Reference Compound 51 by the following way:




To a stirred solution of Reference Compound 51 (4.2 g, 18.18 mmol, 1.00 equiv) in THF (150 mL) was added BH3.Me2S (45 mL, 2M) dropwise at room temperature in 10 mins. The resulting solution was heated to reflux overnight. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 100 mL of methanol. The pH value of the solution was adjusted to 1 with conc. HCl, and the mixture was refluxed for 1 hr. The resulting mixture was concentrated under vacuum. The residue was dissolved in 100 mL of water. Potassium carbonate was employed to adjust the pH to 10. The resulting solution was extracted with THF (4×200 mL) and the combined organic layer was washed with brine (2×200 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 3 g (76%) of Compound 540-1 as a white solid.




To a stirred solution of Compound 540-1 (1.0 g, 4.61 mmol, 1.00 equiv) in DMF (20 mL) was added 2-(tert-butoxycarbonyl)acetic acid (1.2 g, 6.86 mmol, 1.49 equiv) and HATU (5.2 g, 13.68 mmol, 2.97 equiv). The resulting solution was stirred for 4 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 300 mg (17%) of the title compound as a white solid.
Example 556
N-(4-chlorophenyl)-2-(4-fluorophenyl)-6,6,7-trimethyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-amine




Example 556 was prepared from Reference Compound 41 bromination followed by a Pd2(dba)3 mediated amination reaction with 4-chloroaniline. The bromination procedure is shown below:




To a stirred solution of Compound 41-1 (52 mg, 0.20 mmol) in 6 mL of DCM was added Br2 (11.3 μL, 0.22 mmol) in 2 mL of acetic acid. The reaction mixture was stirred at room temperature for 30 mins. Solvent was removed via rotavap at a temperature no higher than 20° C. After neutralization, the residue was subjected to flash chromatography (40 g, 0-10% methanol in DCM, 50 mins, dry loading) purification to give 59 mg (87%) of the title compound as white solid.
Example 645
8-(3,4-difluorophenylamino)-9-(4-fluorophenyl)-2,2-dimethyl-5,6-dihydrodiimidazo[1,2-a:2′,1′-c]pyrazin-3 (2H)-one




Example 645 was prepared from Example 29 by the following method: to a stirred solution of Example 29 (12 mg, 0.03 mmol) was added MnO2 (52 mg, 0.60 mmol). The reaction mixture was stirred at room temperature for 2 hours. LC/MS test showed that Example 29 was almost gone and the desired product ([M+1]=526) was detected as one of the major peaks. Solid was filtered off and solvent was removed. The residue was subjected to a mass-triggered HPLC purification to give Example 645.
Example 646
8-(3,4-difluorophenylamino)-9-(4-fluorophenyl)-2,2-dimethyl-1,2,5,6-tetrahydrodiimidazo[1,2-a:2′,1′-c]pyrazin-3(10bH)-one




Example 646 was prepared from Example 29 by the following method: to a stirred solution of Example 29 (12 mg, 0.03 mmol) was added MnO2 (52 mg, 0.60 mmol). The reaction mixture was stirred at room temperature for 2 hours. LC/MS test showed that Example 29 was almost gone and the desired product ([M+1]=528) was detected as one of the major peaks. Solid was filtered off and solvent was removed. The residue was subjected to a mass-triggered HPLC purification to give Example 646.
Example 687
7-(2-aminoethyl)-2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-7,8-dihydroimidazo[1,2-a]pyrazin-6(5H)-one




Example 687 was prepared from Example 688 by the following steps:




To a stirred solution of Example 688 (22 mg, 0.05 mmol) and Et3N (42 μL, 0.30 mmol) in 3 mL of DCM were added MsCl (12 μL, 0.15 mmol). The reaction mixture was stirred at room temperature for 3 hours. HPLC/MS test showed that Example 688 was all gone and the desired product ([M+1]=519) was formed as the only major peak. Solvent was removed and the residue was subjected to a mass-triggered HPLC purification to give 18 mg of mesylate. To a stirred solution of the mesylate (5 mg, 0.01 mmol) in 2 mL of MeOH was added 1 mL of 5 M in MeOH. The reaction mixture was stirred at 120° C. for 20 minutes in a microwave oven. HPLC/MS test showed that the mesylate was all gone and Example 687 ([M+1]=440) was formed as the one of the major peaks. Solvent was removed and the residue was subjected to a mass-triggered HPLC purification to give 3 mg of Example 687.
Example 692
4-(3-(4-fluoro-3-methylphenylamino)-2-(3-fluorophenyl)-8,8-dimethyl-6-oxo-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)butanoic acid




Example 692 was prepared from Reference Compound 73 by the following steps:




To a solution of Reference Compound 73 (10 mg, 0.03 mmol) in 3 mL of DMF were added KOH (8 mg, 0.12 mmol), and ethyl 4-bromobutanoate (24 mg, 0.12 mmol) at room temperature. The reaction mixture was stirred in a microwave oven at 90° C. for 20 minutes. LC/MS test showed that 50% of starting material was remaining and the desired product ester ([M+1]=497) was the major product. The reaction mixture was filtered and subjected to mass-triggered HPLC purification to give the ester as colorless oil. The obtained ester was hydrolyzed by LiOH to give Example 692.
Example 695
2-amino-1-(2-(4-fluorophenyl)-3-(4-methoxybenzyl)-8,8-dimethyl-5,6-dihydroimidazol[1,2-a]pyrazin-7(8H)-yl)ethanone




Example 695 was prepared from Reference Compound 74 by the following steps:




To a solution of Reference Compound 74 (21 mg, 0.05 mmol) in 3 mL of dry THF was added 2.5 N (0.025 mL, 0.06 mmol) at −78° C. The reaction mixture was stirred at the same temperature for 20 mins and (II) (41 mg, 0.30 mmol) in 1 mL of dry THF was added. The reaction mixture was stirred for another 5 hours while the temperature raised to room temperature. LC/MS test showed that starting material was all gone and the desired adduct Example 695-1 (20 mg, 84%) was isolated as the major product.




To a solution of Example 695-1 (10 mg, 0.021 mmol) in 3 mL of i-PrOH were added 10% Pd/C (3 mg, 0.004 mmol) and 1,4-cyclohexadiene (20 μL, 0.21 mmol). The reaction mixture was stirred at 120° C. for 3 hours in a Q-tube. LC/MS test showed that the starting material was gone and there was a major peak with [M+1]=466, which corresponded to the desired product. Solid was filtered off and solvent was removed. The residue was subjected to mass-triggered HPLC purification to give 16 mg of crude Example 695-2 as brown oil. Example 695-2 was subjected to a TFA mediated deprotection to get 3 mg of Example 695-3 ([M+1]=366).




To a stirred solution of Example 695-3 (4 mg, 0.01 mmol) and 2-(tert-butoxycarbonylamino)acetic acid (5.2 mg, 0.03 mmol) in 2 mL of DMF were added HATU (12 mg, 0.03 mmol) and DIEA (5.2 μL, 0.03 mmol). The reaction mixture was stirred at room temperature for 3 hours. LC/MS test showed that the starting material was almost gone and the desired adduct ([M+1]=523) was formed as the one of the major peaks. The reaction subjected to a mass-triggered HPLC purification to give the adduct, which was subjected to a TFA mediated deprotection to get 6 mg of Example 695 ([M+1]=422).
Example 700
2-amino-1-(2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-3-p-tolylpropan-1-one




Example 700 was prepared from Reference Compound 35 by the following steps:




To a solution of Reference Compound 35 (48 mg, 0.10 mmol) in 3 mL of dry THF was added 2.2 N n-BuLi (0.11 mL, 0.24 mmol) at −78° C. The reaction mixture was stirred at the same temperature for 20 minutes and 1-(bromomethyl)-4-methylbenzene (111 mg, 0.60 mmol) in 1 mL of dry THF was added. The reaction mixture was stirred for another 5 hours while the temperature raised to room temperature. LC/MS test showed that starting material was all gone and adduct. The reaction mixture was quenched with NH4Cl aqueous solution and diluted with ethyl acetate. The organic solution was separated, dried and concentrated. The residue was subjected to a mass-triggered HPLC purification to give 28 mg of the adduct as clear oil. This was subjected to a TFA mediated deprotection to give Example 700.
Example 704
2-amino-1-(2-(4-fluorophenyl)-8,8-dimethyl-3-p-tolyl-5,6-dihydroimidazo-[1,2-a]pyrazin-7(8H)-yl)ethanone




Example 704 was prepared from Reference Compound 35 in the following steps:




Reference Compound 35 (48 mg, 0.10 mmol), p-tolylboronic acid (27 mg, 0.20 mmol), Pd(PPh3)4 (12 mg, 0.01 mmol), and 1.0 N Na2CO3 (0.20 mL, 0.20 mmol) were combine in a 40 mL vial. 5 mL of THF was added. The reaction mixture was de-gassed by repeated evacuation and re-fill with nitrogen. And the reaction mixture was stirred at 70° C. for 2 hours. LC/MS test showed that Reference Compound 35 was almost gone and the desired adduct was detected as one of the major peaks. Solid was filtered and solvent was removed. The residue was subjected to a mass-triggered HPLC purification to give 22 mg of the desired adduct. This was subjected to a TFA mediated deprotection to give Example 704.
Example 707
N,2-bis(4-fluorophenyl)-8,8-dimethyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-3-carboxamide




Example 707 was prepared from Reference Compound 74 by the following steps:




To a solution of Reference Compound 74 (21 mg, 0.05 mmol) in 3 mL of dry THF was added 2.5 N n-BuLi (0.04 mL, 0.10 mmol) at −78° C. The reaction mixture was stirred at the same temperature for 20 mins and 1-fluoro-4-isocyanatobenzene (33 μL, 0.30 mmol) in 1 mL of dry THF was added. The reaction mixture was stirred for another 5 hours while the temperature raised to room temperature. LC/MS test showed that starting material was all gone and the desired adduct was detected as a major peak. Solid was filtered and solvent was removed. The residue was subjected to mass-triggered HPLC purification to give 56 mg of the desired adduct as brown oil. The adduct was subjected to a TFA mediated deprotection to get 22 mg of Example 707 ([M+1]=393) as yellow solid.
Example 709
2-amino-1-(3-(4-fluorophenoxy)-2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone




Example 709 was prepared from Reference Compound 35 in the following steps:




To a solution of Reference Compound 35 (48 mg, 0.10 mmol) in 5 mL of dioxane were added 4-fluorophenol (34 mg, 0.30 mmol), CuI (3.8 mg, 0.02 mmol), N,N-dimethylglycine (4.1 mg, 0.04 mmol) and Cs2CO3 (98 mg, 0.30 mmol) at room temperature. The reaction mixture was degassed and stirred at 120° C. under N2 overnight. LC/MS test showed that the starting material was all gone and the desired adduct ([M+1]=513) was detected as a major peak. Solid was filtered and solvent was removed. The residue was subjected to a mass-triggered HPLC purification to give 28 mg of the desired adduct. This was deprotected with TFA to give Example 709.
Example 713
2-amino-1-(2-(4-fluorophenyl)-8,8-dimethyl-3-(p-tolylthio)-5,6-dihydro imidazo[1,2-a]pyrazin-7(8H)-yl)ethanone




Example 713 was prepared from Reference Compound 35 in the following steps:




To a solution of Reference Compound 35 (24 mg, 0.05 mmol) in 3 mL of dioxane were added 4-methylbenzenethiol (17 mg, 0.15 mmol), Pd2(dba)3 (9.2 mg, 0.01 mmol), XantPhos (12 mg, 0.02 mmol) and Cs2CO3 (33 mg, 0.10 mmol) at room temperature. The reaction mixture was degassed and stirred at 150° C. under N2 overnight. LC/MS test showed that about 50% of the starting material was remaining and the desired adduct was one of the major peaks ([M+1]=525). Solid was filtered and solvent was removed. The residue was subjected to mass-triggered HPLC purification to give 32 mg of the adduct as brown oil. This was deprotected with TFA to give Example 713.
Example 721
2-amino-1-(2-(4-fluorophenyl)-8,8-dimethyl-3-(p-tolylsulfinyl)-5,6-dihydro imidazo[1,2-a]pyrazin-7 (8H)-yl)ethanone




Example 721 was prepared from Reference Compound 35 in the following steps:\




To a solution of Reference Compound 35 (24 mg, 0.05 mmol) in 3 mL of dioxane were added 4-methylbenzenethiol (17 mg, 0.15 mmol), Pd2(dba)3 (9.2 mg, 0.01 mmol), XantPhos (12 mg, 0.02 mmol) and Cs2CO3 (33 mg, 0.10 mmol) at room temperature. The reaction mixture was degassed and stirred at 150° C. under N2 overnight. LC/MS test showed that about 50% of the starting material was remaining and the desired adduct was one of the major peaks ([M+1]=525). Solid was filtered and solvent was removed. The residue was subjected to mass-triggered HPLC purification to give 32 mg of the adduct as brown oil. To a solution of the adduct (32 mg, 0.061 mmol) in 10 mL of DCM was added mCPBA (63 mg, 0.37 mmol) at 0° C. The reaction mixture was stirred at the same temperature for 20 mins allowed to warm to room temperature. LC/MS test showed that starting material was all gone and the desired sulfoxide ([M+1]=557) was the major peak. The reaction mixture was quenched with NH4Cl aqueous solution and diluted with ethyl acetate. The organic solution was separated, dried and concentrated. The residue was subjected to a mass-triggered HPLC purification to give 27 mg of the desired sulfoxide as clear oil. This was deprotected with TFA to give Example 721.
Example 730
N-(3-(2-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7 (8H)-yl)-2-oxoethylamino)propyl)-3-phenylpropanamide




Example 730 was prepared from Reference Compound 75 by the following way:




To a solution of Reference Compound 75 (10 mg, 0.02 mmol) in 2 mL of DMF were added N-(3-aminopropyl)-3-phenylpropanamide (9 mg, 0.04 mmol) and Et3N (21 μL, 0.15 mmol) at room temperature. The reaction mixture was stirred at room temperature for 3 hours. HPLC/MS test showed that the starting material was gone and the desired product ([M+1]=601) was detected as a major peak. Reaction mixture was subjected to mass-triggered HPLC purification to give 8 mg of Example 730.
By repeating the procedures described in the above examples, using appropriate starting materials, the following compounds of Formula Ia, Ib or Ic, as identified in Table 2, are obtained. Table 2 also documents the physical data obtained from the associated examples above.











TABLE 2







Physical Data
EC50 3D7
EC50 W2


Com-

MS (m/z) and/or
strain
strain


pound
Structure
1H NMR
(μM)
(μM)



















1




392.5 (M + 1)
0.46
0.473


 


2




376.4 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.93 (d, J = 7.6 Hz, 2H); 7.33 (t, J = 7.6 Hz, 2H); 6.97 (d, J = 7.6 Hz, 1H); 5.08 (m, 1H); 4.85- 4.67 (m, 2H); 3.93-3.38 (m, 6H); 2.17-2.08 (ss, 6H)
3.48
3.348


 


3




412.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.70- 7.67 (m, 2H); 7.22 (t, J = 8.8 Hz, 2H); 6.97 (t, J = 8.8 Hz, 2H), 6.8-6.77 (m, 2H); 5.16 (s, 2H); 4.24 (m, 2H), 4.07 (m, 2H); 1.76 (s, 6H). Elemental Analysis: (compound + 2 HCl + 0.50 H2O): Elemental Analysis: % C, 53.56; H, 5.31; N, 14.19 (calculated). % C = 53.98/53.69; % N = 14.07/13.97; % H =  516/4.98 (experimental).
0.02
0.025


 


4




384.2 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.59-7.56 (m, 2H); 7.12 (t, J = 8.8 Hz, 2H); 6.86 (t, J = 8.8 Hz, 2H); 6.68-6.65 (m, 2H); 5.04-5.00 (m, 2H); 4.08- 3.92 (m, 6H).
0.02
0.023


 


5




438.2 (M + 1)
4.33
>8.9


 


6




358.4 (M + 1)
4.38
4.643


 


7




340.4 (M + 1)
15.82
7.78


 


8




376.4 (M + 1)
0.62
0.501


 


9




434.4 (M + 1)
13.84
3.988


 


10




412.4 (M + 1)
1.39
1.284


 


11




394.4 (M + 1)
0.2
0.168


 


12




448.4 (M + 1)
7.4
2.956


 


13




430.4 (M + 1)
0.26
0.137


 


14




464.5 (M + 1)
3.59
5.871


 


15




400.4 (M + 1)
2.63
2.111


 


16




395.4 (M + 1)
14.13
3.325


 


17




398.4 (M + 1)
0.09
0.064


 


18




412.2 (M + 1)
12.27
8.139


 


19




474.2 (M + 1)
0.07
0.059


 


20




474.2 (M + 1)
0.11
0.121


 


21




474.0 (M + 1)
0.1
0.078


 


22




412.2 (M + 1)
1.3
0.691


 


23




408.2 (M + 1)
>10.58
10.489


 


24




320.3 (M + 1)
8.92
2.862


 


25




426.2 (M + 1)
>10.6
4.347


 


26




323.3 (M + 1)
>10
5.521


 


27




400.2 (M + 1)
9.61
5.984


 


28




327.2 (M + 1) 1H-NMR (300 MHz, DMSO-d6): δ 7.81-7.72 (m, 2H), 7.11 (m, 2H), 6.97 (m, 2H), 6.56-6.52 (m, 2H), 3.86 (s, 2H), 3.55 (m, 2H), 3.02 (m, 2H)
0.2
0.175


 


29




430.2 (M + 1) 1H-NMR (400 MHz, MeOH-d4) δ 7.64-7.70 (m, 1H); 6.95- 6.91 (m, 3H); 6.33-6.39 (m, 1H); 6.27-6.22 (m, 1H); 4.97 (s, 2H); 4.17 (m, 2H); 3.73 (t, J = 2.8 Hz, 2H); 1.36 (s, 6H). Elemental Analysis: (compound + 2HCl + 0.40 H2O): Elemental Analysis: % C, 51.85; % H, 4.91; % N, 13.74; (calculated). % C = 51.73, 51.85; % N =  13.5.13.51; % H = 4.87, 4.94 (experimental).
0.03
0.036


 


30




402.1 (M + 1) 1H-NMR MeOH-d4, (400 Hz) δ 7.64- 7.59 (m, 2H); 6.96-6.89 (m, 2H); 6.38- 6.34 (m, 1H); 6.27-6.23 (m, 1H); 4.74-4.63 (m, 2H); 3.94- 3.41 (m, 6H). 
0.03
0.023


 


31




397.2 (M + 1)
13.08
6.893


 


32




398.2 (M + 1)
0.21
0.219


 


33




438.2 (M + 1)
0.74
1.617


 


34




398.4 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.64-7.60 (m, 2H); 6.93- 6.87 (m, 2H); 6.80-6.75 (m, 2H); 6.49- 6.45 (m, 2H); 4.71-4.70 (m, 2H); 3.85 (t, J = 5.2 Hz, 1H); 3.82 (t, J = 5.2 Hz, 1H) 3.72 (t, J = 5.2 Hz, 1H); 3.63 (t, J = 5.2 Hz, 1H); 2.83 (m, 2H); 2.54 (m, 2H).
0.07
0.075


 


35




412.2 (M + 1)
0.12
0.105


 


36




384.4 (M + 1)
0.05
0.034


 


37




408.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.72 (m, 2H); 7.18 (t, J = 8.0 Hz, 2H); 7.02 (m, 2H), 6.7 (m, 2H); 5.19 (s, 2H); 4.07 (m, 2H), 2.21 (s, 6H); 1.77 (s, 6H)
0.05
0.043


 


38




380.4 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.74-7.71 (m, 2H); 7.21- 7.17 (m, 2H); 7.03 (t, J = 8.0 Hz, 2H); 6.67 (d, J = 8.4 Hz, 2H); 5.17-5.15 (m, 2H); 4.22- 3.98 (m, 6H); 2.22 (s, 3H).
0.01
0.013


 


39




428.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.70 (m, 2H); 7.21 (m, 4H); 6.8 (m, 2H), 4.26 (m, 2H); 4.0 (m, 2H), 1.77 (s, 6H)
0.02
0.024


 


40




400.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.59- 7.56 (m, 2H); 7.15-7.09 (m, 4H); 6.68-6.65 (m, 2H), 5.05 (m, 2H); 4.04- 3.87 (m, 6H).
0.01
0.009


 


41




454.2 (M + 1)
2.65
1.79


 


42




502.3 (M + 1)
6.1
4.611


 


43




488.2 (M + 1)
0.18
0.149


 


44




385.2 (M + 1)
0.72
0.477


 


45




410.2 (M + 1)
0.98
1.335


 


46




454.2 (M + 1)
13.99
3.11


 


47




409.2 (M + 1)
6.98
6.183


 


48




417.2 (M + 1)
1.84
1.752


 


49




518.2 (M + 1)
2.29
1.9


 


50




452.2 (M + 1)
0.18
0.187


 


51




400.2 (M + 1)
0.07
0.062


 


52




380.2 (M + 1)
3.14
3.36


 


53




396.2 (M + 1)
2.27
1.703


 


54




445.3 (M + 1)
1.29
0.764


 


55




400.3 (M + 1)
0.66
0.437


 


56




384.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.55- 7.53 (m, 1H); 7.47-7.45 (m, 2H); 7.15 (m, 1H); 6.96- 6.94 (m, 2H); 6.84-6.81 (m, 2H); 5.20 (m, 2H); 4.25-4.20 (m, 6H), 3.35 (s, NH).
0.01
0.013


 


57




474.2 (M + 1)
0.31
0.294


 


58




456.2 (M + 1)
0.47
0.28


 


59




456.2 (M + 1)
1.09
0.735


 


60




470.2 (M + 1)
2.46
2.129


 


61




520.2 (M + 1)
9.24



 


62




488.2 (M + 1)
4.74
4.738


 


63




520.2 (M + 1)
1.95
1.606


 


64




468.2 (M + 1)
9.37
6.465


 


65




448.2 (M + 1)
0.47
0.509


 


66




430.2 (M + 1)
0.22
0.244


 


67




402.2 (M + 1)
0.19
0.197


 


68




424.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.71- 7.67 (m, 2H); 7.22 (t, J = 8.8 Hz, 2H); 6.97- 6.95 (m, 2H), 6.8-6.77 (m, 2H); 5.15 (s, 2H); 4.19-3.99 (m, 4H), 3.74- 3.58 (m, 2H); 2.9-2.82 (m, 1H); 0.98- 0.97 (m, 4H).
0.15
0.264


 


69




440.2 (M + 1)
0.08
0.094


 


70




412.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.50- 7.48 (m, 2H); 7.44-7.40 (m, 2H); 7.18 (m, 1H); 6.98 (t, J = 8.8 Hz, 2H); 6.82-6.79 (m, 2H); 5.18 (m, 2H); 4.25 (t, J = 4.8 Hz, 2H); 4.07 (t, J = 4.8 Hz, 2H); 1.76 (s, 6H)
0.05
0.079


 


71




418.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.7 (m, 2H); 7.28- 7.22 (m, 2H); 6.71 (m, 1H); 6.64 (m, 1H); 5.16 (s, 2H); 4.18-4.01 (m, 6H)
0.0
0.004


 


72




462.2 (M + 1)
0.95
0.589


 


73




434.2 (M + 1)
0.08
0.059


 


74




484.2 (M + 1)
0.07
0.067


 


75




394.2 (M + 1)
0.25
0.19


 


76




504.2 (M + 1)
0.06
0.061


 


77




414.2 (M + 1)
0.06
0.039


 


78




418.0 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.72-7.68 (m, 2H); 7.23 (t, J = 8.8 Hz, 2H); 7.08 (t, J = 8.8 Hz, 1H); 6.91 (dd, J =  3.2 Hz, J = 5.8 Hz, 1H); 5.16 (m, 2H); 4.22- 4.05 (m, 6H)
0.01



 


79




430.2 (M + 1)
0.11
0.09


 


80




402.2 (M + 1)
0.06
0.063


 


81




395.2 (M + 1)
0.3
0.449


 


82




457.2 (M + 1)
0.0
0.007


 


83




394.2 (M + 1)
0.08
0.131


 


84




394.2 (M + 1)
0.05
0.074


 


85




408.2 (M + 1)
0.02
0.031


 


86




434.2 (M + 1)
0.71
0.755


 


87




434.2 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.71-7.68 (m, 2H); 7.21 (t, J = 8.8 Hz, 2H); 7.03 (d, J = 8.0 Hz, 2H) 6.67 (d, J = 8.4 Hz, 2H); 5.35- 4.96 (m, 2H); 4.37-3.88 (m, 4H); 3.49-3.31 (m, 3H); 3.25- 3.13 (m, 2H); 2.23 (s, 3H); 2.11-1.8 (m, 4H)
0.02
0.012


 


88




422.6 (M + 1)
0.15
0.081


 


89




406.2 (M + 1)
0.05
0.073


 


90




420.2 (M + 1)
0.65
0.6


 


91




420.2 (M + 1)
0.12
0.154


 


92




434.2 (M + 1)
1.3
1.484


 


93




434.2 (M + 1)
1.67
1.512


 


94




446.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.59- 7.56 (m, 2H); 7.2-7.11 (m, 3H); 6.6-6.57 (m, 2H); 5.04 (s, 2H); 4.14 (m, 2H); 3.97 (m, 2H); 1.69 (s, 6H).
0.04
0.052


 


95




420.2 (M + 1)
1.54
0.707


 


96




420.2 (M + 1)
0.58
0.321


 


97




456.2 (M + 1)
0.04
0.021


 


98




456.2 (M + 1)
0.01
0.008


 


99




407.2 (M + 1)
0.81
0.658


 


100




423.2 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.78-7.68 (m, 2H); 7.16 (t, J = 8.8 Hz, 2H); 7.02 (d, J = 8.0 Hz, 2H) 6.64-6.60 (m, 2H); 5.17-5.07 (m, 2H); 4.13- 3.86 (m, 4H); 2.7 (s, 2H); 2.22 (2, 3H); 1.32 (s, 6H).
0.15
0.143


 


101




493.6 (M + 1)
5.09
4.373


 


102




547.6 (M + 1)
0.65
0.426


 


103




395.2 (M + 1)
1.02



 


104




423.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.76- 7.73 (m, 2H); 7.02-6.95 (m, 4H); 6.49 (m, 2H), 4.96- 4.80 (m, 2H); 4.25-4.08 (m, 1H); 3.83-3.73 (m, 2H); 3.76- 3.73 (m, 2H); 2.20 (s, 3H); 1.98 (m, 1H); 0.96 (t, J = 6.8 Hz, 6H).
0.01
0.007


 


105




435.2 (M + 1)
0.85



 


106




471.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.64- 7.59 (m, 2H); 7.13-6.85 (m, 9 H); 6.83 (t, J = 8.4 Hz, 2H); 4.73-4.35 (m, 3H); 3.94-3.49 (m, 4H); 4.03- 3.87 (m, 2H); 2.93-2.88 (m, 2H); 2.11 (s, 3H).
0.0
0.004


 


107




475.2 (M + 1)
0.01
0.01


 


108




409.2 (M + 1)
0.96



 


109




471.2 (M + 1)
0.04



 


110




437.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.65- 7.62 (m, 2H); 6.92-6.84 (m, 4 H); 6.49 (m, 2H), 6.39 (t, J = 8.8 Hz, 2H).4.95-4.62 (m, 2H); 4.18 (d, J = 8.4 Hz, 1H); 4.03-3.87 (m, 2H); 3.74- 3.64 (m, 2H); 2.1 (s, 3H); 0.9 (d, J = 7.2 Hz, 9H).
0.02
0.015


 


111




471.2 (M + 1)
0.02



 


112




533.6 (M + 1)
1.43



 


113




323.2 (M + 1) 1H NMR (400 MHz, CD3OD) 7.73 (d, J = 6.8 Hz, 2H), 7.00-6.99 (m, 4H), 6.49 (d, J = 8.0 Hz, 2H), 4.01 (s, 2H), 3.72 (s, 2H), 3.15 (s, 2H), 2.19 (s, 3H).
0.15
0.146


 


114




409.2 (M + 1)
1.34
1.35


 


115




477.2 (M + 1)
0.15
0.153


 


116




435.2 (M + 1)
1.64
1.509


 


117




449.2 (M + 1)
1.26
1.186


 


118




485.6 (M + 1)
0.15
0.135


 


119




513.4 (M + 1)
4.74



 


120




477.2 (M + 1)
0.11
0.123


 


121




463.4 (M + 1)
0.02
0.033


 


122




487.2 (M + 1)
0.18
0.154


 


123




493.2 (M + 1)
0.03



 


124




525.2 (M + 1)
0.04
0.028


 


125




471.3 (M + 1)
0.05
0.044


 


126




536.2 (M + 1)
0.1
0.08


 


127




525.4 (M + 1)
0.06
0.051


 


128




539.2 (M + 1)
1.18
0.743


 


129




473.2 (M + 1)
0.01
0.006


 


130




473.2 (M + 1)
0.01



 


131




492.0 (M + 1)
0.04
0.03


 


132




554.2 (M + 1)
0.1
0.082


 


133




492.0 (M + 1)
0.05
0.039


 


134




437.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.76- 7.73 (m, 2H); 7.02-6.95 (m, 4 H); 6.50 (d, J = 7.2 Hz, 2H), 4.95-4.72 (m, 2H); 4.59- 4.51 (m, 1H); 4.08-3.51 (m, 4H); 2.20 (s, 3H); 1.86 (m, 1H); 1.59 (m, 1H); 1.48 (m, 1H); 0.96 (d, J = 7.2 Hz, 6H),
0.01
0.007


 


135




471.2 (M + 1)
0.05
0.033


 


136




319.1 (M + 1) 1H NMR (400 MHz, CD3OD) 9.04 (s, 1H); 8.03 (dd, J = 1.2 Hz, J = 4.8 Hz, 1H), 7.97 (m, 2H), 6.90 (d, J = 8.0 Hz, 2H), 6.41 (d, J = 8.4 Hz, 2H) 2.1 (s, 3H).
2.02
2.693


 


137




457.2 (M + 1)
0.01
0.012


 


138




457.2 (M + 1)
0.01
0.015


 


139




420.2 (M + 1)
0.16
0.165


 


140




434.2 (M + 1)
0.09
0.128


 


141




448.2 (M + 1)
0.07
0.09


 


142




462.4 (M + 1)
0.08
0.12


 


143




437.2 (M + 1)
0.15
0.219


 


144




448.2 (M + 1)
0.05
0.073


 


145




477.5 (M + 1)
0.09
0.068


 


146




470.5 (M + 1)
0.02
0.014


 


147




464.5 (M + 1)
2.43
1.519


 


148




478.5 (M + 1)
4.06
1.432


 


149




484.5 (M + 1)
0.02
0.011


 


150




642.5 (M + 1)
0.96
0.673


 


151




628.5 (M + 1)
0.82
0.386


 


152




685.4 (M + 1)
3.87
0.873


 


153




420.5 (M + 1)
0.06
0.032


 


154




493.5 M + 1)
4.27
3.411


 


155




671.6 (M + 1)
2.14
0.491


 


156




451.5 (M + 1)
1.83
0.458


 


157




485.5 (M + 1)
0.1
0.097


 


158




521.5 (M + 1)
7.54
4.763


 


159




925.1 (M + 1)
5.7
2.91


 


160




527.5 (M + 1)
4.32
2.39


 


161




468.2 (M + 1)
0.54
0.51


 


162




420.5 (M + 1)
1.78
1.376


 


163




410.1 (M + 1)
0.02
0.026


 


164




506.2 (M + 1)
>9.81
3.757


 


165




461.2 (M + 1)
>10.23
4.642


 


166




423.2 (M + 1)
2.87
2.229


 


167




422.2 (M + 1)
0.18
0.145


 


168




456.2 (M + 1)
0.01
0.011


 


169




422.5 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.59- 7.56 (m, 2H); 7.13-7.00 (m, 2 H); 6.95-6.93 (m, 2H); 6.56- 6.54 (m, 2H); 5.17-4.8 (m, 2H); 4.37-3.72 (m, 5H); 1.23- 1.19 (m, 1H); 1.03 (d, J = 8.8 Hz, 3 H); 1.03 (d, J = 8.8 Hz, 3 H); 0.95 (d, J = 8.8 Hz, 3H).
0.04



 


170




436.2 (M + 1)
0.09
0.054


 


171




563.2 (M + 1)
0.17
0.214


 


172




538.4 (M + 1)
0.1
0.088


 


173




489.2 (M + 1)
0.14
0.133


 


174




503.5 (M + 1)
6.06
1.475


 


175




455.2 (M + 1)
0.08
0.105


 


176




472.2 (M + 1)
2.75
1.791


 


177




498.5 (M + 1)
0.43
0.43


 


178




491.5 (M + 1)
3.05
3.321


 


179




491.5 (M + 1)
4.79
1.072


 


180




498.5 (M + 1)
0.73
0.609


 


181




511.5 (M + 1)
2.68
1.811


 


182




484.5 (M + 1)
1.37
1.076


 


183




514.5 (M + 1)
1.9
1.342


 


184




490.5 (M + 1)
3.65
0.859


 


185




641.3 (M + 1)
0.35
0.136


 


186




579.3 (M + 1)
5.63
2.56


 


187




541.3 (M + 1)
6.68
3.551


 


188




493.6 (M + 1)
0.79
1.097


 


189




479.6 (M + 1)
0.37
0.392


 


190




462.2 (M + 1)
0.94
1.073


 


191




327.2 (M + 1) 1H-NMR: (300 MHz, DMSO-d6): δ 2.50-2.52 (2H, t, J = 1.5 Hz), 3.54-3.58 (2H, t, J = 2.1 Hz), 3.87 (s, 2H), 6.53-6.58 (m, 2H), 6.91-7.02 (m, 3H), 7.27- 7.36 (m, 1H), 7.50 (1H, d, J = 10.5 Hz), 7.62 (1H, d, J = 7.8 Hz), 7.79 (s, 1H)
0.17
0.151


 


192




361.1 (M + 1) 1H NMR (400 MHz, CDCl3) δ 7.75-7.70 (m, 2H) 7.25-7.19 (m, H), 7.05- 7.02 (m, 2H), 6.48-6.41 (m, 2H), 4.16 (s, 2H), 3.70 (m, 2H), 3.24 (m, 2H).
0.11
0.095


 


193




434.2 (M + 1)
0.09
0.075


 


194




486.2 (M + 1)
0.05



 


195




452.1 (M + 1)
0.02
0.02


 


196




452.1 (M + 1)
0.32
0.344


 


197




555.3 (M + 1)
4.16
1.04


 


198




409.2 (M + 1)
1.36



 


199




421.2 (M + 1)
0.24
0.157


 


200




421.2 (M + 1)
0.91



 


201




485.6 (M + 1)
0.24
0.131


 


202




471.2 (M + 1)
0.16
0.102


 


203




505.1 (M + 1)
0.97
0.369


 


204




423.2 (M + 1)
0.01
0.01


 


205




423.2 (M + 1)
0.0
0.004


 


206




443.2 (M + 1)
1.2
1.17


 


207




357.1 (M + 1)
9.31
2.421


 


208




513.2 (M + 1)
5.87
1.057


 


209




435.2 (M + 1)
11.62
4.362


 


210




515.2 (M + 1)
0.04
0.026


 


211




435.2 (M + 1)
0.3
0.283


 


212




421.2 (M + 1)
1.95
1.984


 


213




499.1 (M + 1)
3.8
4.823


 


214




476.3 (M + 1)
2.85
2.008


 


215




435.2 (M + 1)
0.83
0.65


 


216




449.2 (M + 1)
0.3
0.248


 


217




361.1 (M + 1) 1H NMR (300 MHz, DMSO-d6) δ 3.04 (2H, t, J = 5.1 Hz), 3.57 (s, 2H), 3.88 (s, 2H), 6.42-6.52 (m, 2H), 6.94- 7.00 (m, 1H), 7.28-7.38 (m, 2H), 7.48 (1H, d, J = 7.2 Hz), 7.58 (1H, d, J = 7.8 Hz), 8.27 (s, 1H)
0.13
0.106


 


218




569.0 (M + 1)
4.71
4.015


 


219




555.9 (M + 1)
4.97
3.414


 


220




448.2 (M + 1)
1.13
0.937


 


221




486.0 (M + 1)
0.09
0.083


 


222




493.0 (M + 1)
0.14
0.103


 


223




493.0 (M + 1)
0.26
0.206


 


224




469.1 (M + 1)
0.02
0.018


 


225




469.1 (M + 1)
0.55
0.316


 


226




509.1 (M + 1)
0.48
0.348


 


227




442.2 (M + 1)
0.09
0.103


 


228




417.9 (M + 1)
0.01
0.008


 


229




446.2 (M + 1)
0.01
0.007


 


230




510.2 (M + 1)
0.32
0.255


 


231




483.3 (M + 1)
0.09
0.07


 


232




455.2 (M + 1)
0.05
0.044


 


233




459.2 (M + 1)
0.01
0.015


 


234




461.0 (M + 1)
0.13
0.111


 


235




427.2 (M + 1)
0.54
0.496


 


236




666.2 (M + 1)
5.25
2.063


 


237




632.3 (M + 1)
7.19
5.722


 


238




653.2 (M + 1)
3.56
1.305


 


239




619.3 (M + 1)
1.84
0.629


 


240




576.2 (M + 1)
10.49
6.99


 


241




542.2 (M + 1)
5.27
2.36


 


242




624.1 (M + 1)
2.09
0.288


 


243




589.3 (M + 1)
2.97
0.697


 


244




423.2 (M + 1)
2.4
1.329


 


245




439.2 (M + 1)
2.53
1.804


 


246




585.3 (M + 1)
3.88
1.791


 


247




618.1 (M + 1)
1.42
3.937


 


248




583.3 (M + 1)
7.01
4.559


 


249




334.3 (M + 1)
5.39
5.055


 


250




611.7 (M + 1)
3.88
3.979


 


251




463.3 (M + 1)
3.68
2.548


 


252




707.3 (M + 1)
3.03
0.631


 


253




679.2 (M + 1)
0.78
0.254


 


254




673.4 (M + 1)
3.44
0.727


 


255




517.3 (M + 1)
0.61
0.653


 


256




483.2 (M + 1)
1.16
1.475


 


257




511.3 (M + 1)
6.68
7.003


 


258




608.1 (M + 1)
4.92
3.513


 


259




579.2 (M + 1)
5.32
3.022


 


260




573.3 (M + 1)
7.64
5.009


 


261




545.1 (M + 1)
7.06
4.126


 


262




343.1 (M + 1) 1H NMR: (DMSO, ppm): δ 7.94 (s, 1H), 7.80-7.74 (m, 2H), 7.18- 7.09 (m, 4H), 6.56 (d, J =  8.7 Hz, 2H), 3.87 (s, 2H), 3.55 (s, 2H), 3.02 (t, J =  5.4 Hz, 2H).
0.24
0.267


 


263




419.2 (M + 1)
0.35
0.653


 


264




391.2 (M + 1)
0.11
0.154


 


265




434.2 (M + 1)
1.35
1.585


 


266




319.2 (M + 1) 1H NMR: (300 MHz, CDCl3) δ 7.70 (s, 1H), 7.56 (1H, d, J =  7.8 Hz), 7.21- 7.15 (1H, t, J =  7.5 Hz), 7.04 (3H, d, J = 8.1 Hz), 5.21 (1H, s), 4.18 (s, 2H), 3.73-3.68 (t, 2H, J =  5.4 Hz), 3.23- 3.18 (t, 2H, J = 5.4 Hz), 2.34 (s, 3H), 2.29 (s, 3H)
1.17
1.313


 


267




655.4 (M + 1)
0.99
0.474


 


268




513.2 (M + 1)
0.01
0.012


 


269




527.2 (M + 1)
0.01
0.006


 


270




541.2 (M + 1)
0.05



 


271




479.0 (M + 1)
0.44
0.385


 


272




555.7 (M + 1)
3.59
3.26


 


273




531.7 (M + 1)
3.33
3.471


 


274




517.7 (M + 1)
5.14
5.673


 


275




529.3 (M + 1)
3.83
3.95


 


276




506.1 (M + 1)




 


277




465.1 (M + 1)




 


278




341.2 (M + 1) 1H NMR (400 MHz, CDCl3) δ 7.70-7.53 (m, 2H), 7.12-7.04 (m, 3H), 6.58 (d, J = 8.4 Hz, 2H), 5.12 (s, 1H), 4.18 (s, 2H), 3.73 (m, 2H), 3.23 (m, 2H), 2.98 (s, 1H), 2.29 (s, 3H).
0.21
0.269


 


279




339.1 (M + 1) 1H NMR (300 MHz, CDCl3) δ 7.70-7.62 (m, 1H), 7.24- 7.15 (m, 2H), 7.05 (d, J = 8.1 Hz, 2H), 6.59 (d, J =  8.1 Hz, 2H), 5.15 (s, 1H), 4.18 (s, 2H), 3.72 (m, 2H), 3.22 (m, 2H), 2.29 (s, 3H)
3.52
3.828


 


280




341.2 (M + 1) 1H NMR (300 MHz, CDCl3) δ 7.70- 7.62 (m, 1H), 7.01 (d, J =  8.1 Hz, 2H), 6.92-6.76 (m, 2H), 6.52 (d, J = 8.1 Hz, 2H), 5.33 (s, 1H), 4.23 (s, 2H), 3.77 (m, 2H), 3.26 (m, 2H), 2.25 (s, 3H).
4.71
4.652


 


281




566.3 (M + 1)
0.82
0.596


 


282




566.3 (M + 1)
0.12
0.117


 


283




527.3 (M + 1)
5.52
3.494


 


284




410.2 (M + 1)
0.05
0.037


 


285




424.2 (M + 1)
0.18
0.177


 


286




486.1 (M + 1)
1.38
1.502


 


287




438.2 (M + 1)
4.36
7.262


 


288




472.2 (M + 1)
0.89
1.388


 


289




436.1 (M + 1)
3.88
0.747


 


290




512.2 (M + 1)
0.44
0.397


 


291




526.2 (M + 1)
1.2
0.567


 


292




375.1 (M + 1) 1H NMR: (300 MHz, CDCl3): δ 7.66- 7.60 (m, 2H), 7.29-7.21 (m, 1H), 7.01-6.99 (m, 2H), 6.55- 6.50 (m, 1H), 6.43-6.40 (m, 1H), 4.28 (s, 2H), 3.75-3.64 (m, 2H), 3.32- 3.25 (m, 5H)
0.15
0.156


 


293




432.0 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.47- 7.43 (m, 2H); 7.27-7.22 (m, 1 H); 7.14-7.07 (m, 2H); 6.7 (m, 1H); 6.53 (m, 1H); 4.99- 4.80 (m, 2H); 4.04 (m, 2H); 3.85 (m, 4 H).
0.02



 


294




460.2 (M + 1)
0.11
0.113


 


295




512.4 (M + 1)
0.21
0.283


 


296




526.7 (M + 1)
0.28
0.424


 


297




289.2 (M + 1) 1H NMR: (300 MHz, CDCl3): 7.72-7.75 (m, 2H), 7.03- 7.10 (m, 2H), 4.16 (s, 2H), 3.86 (t, J = 5.4 Hz, 2H), 3.23 (t, J =  5.4 Hz, 2H), 1.04 (s, 9H).
5.29
8.505


 


298




930.5 (M + 1)
0.61
0.193


 


299




337.2 (M + 1)
>8.74
9.398


 


300




337.2 (M + 1)
1.11
1.169


 


301




462.2 (M + 1)
0.03
0.047


 


302




480.2 (M + 1)
0.17
0.149


 


303




518.3 (M + 1)
0.54
0.439


 


304




516.2 (M + 1)
3.21
2.946


 


305




494.2 (M + 1)
0.09
0.094


 


306




519.2 (M + 1)
0.42
0.334


 


307




422.2 (M + 1)
0.03
0.022


 


308




450.3 (M + 1)
0.06
0.068


 


309




438.2 (M + 1)
0.08
0.068


 


310




452.2 (M + 1)
0.52
0.397


 


311




509.0 (M + 1)
0.09
0.072


 


312




553.0 (M + 1)
1.64
0.897


 


313




460.2 (M + 1)
0.02
0.004


 


314




432.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.59- 7.55 (m, 2H); 7.22-7.12 (m, 3 H); 6.60-6.51 (m, 2H); 5.13- 4.89 (m, 2H); 4.49 (m, 2H); 4.02-3.90 (m, 3H); 1.43 (d, J = 6.8 Hz, 3H).
0.03
0.02


 


315




515.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 8.94- 8.90 (m, 2H); 7.59-7.44 (m, 2 H); 7.21-7.13 (m, 3H); 6.59- 6.51 (m, 2H); 5.24-5.09 (m, 2H); 4.04-3.85 (m, 5H); 3.38- 3.28 (m, 2H).
0.02
0.008


 


316




526.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.59- 7.52 (m, 2H); 7.27-7.22 (m, 2 H); 7.03-6.92 (m, 2H); 6.53- 6.44 (m, 2H); 5.17 (m, 1H); 4.23 (m, 1H); 3.92-3.72 (m, 3H); 3.51-3.42 (m, 2H); 3.22 (m, 1H); 3.09- 3.06 (m, 1H).
0.02
0.014


 


317




474.0 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.59- 7.56 (m, 2H); 7.22-7.11 (m, 3 H); 6.58-6.49 (m, 2H); 5.2- 4.88 (m, 2H); 4.5-3.62 (m, 5H); 1.91-1.88 (m, 1H); 1.5- 1.46 (m, 1H); 1.27-0.87 (m, 7H).
0.02



 


318




460.2 (M + 1)
0.15
0.098


 


319




544.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.58- 7.53 (m, 2H); 7.22-7.12 (m, 6 H); 6.59-6.49 (m, 2H); 5.3- 5.25 (m, 1H); 4.93-4.73 (m, 2H); 4.05-3.65 (m, 4H); 3.15-- 3.1 (m, 1H); 3.07-2.97 (m, 1H).
0.04
0.027


 


320




460.2 (M + 1)
0.17
0.103


 


321




444.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.58- 7.55 (m, 2H); 7.22-7.14 (m, 3 H); 6.61-6.51 (m, 2H); 5034- 5.20 (m, 2H); 4.53-4.39 (m, 2H); 4.15-4.1 (m, 2H); 4.02- 3.95 (m, 3H); 1.18 (m, 1H); 1.06 (d, J = 7.2 Hz, 2H); 0.963 (d, J = 7.2 Hz, 2H).
0.02
0.011


 


322




474.2 (M + 1)
0.04



 


323




474.2 (M + 1)
1.73
1.329


 


324




508.2 (M + 1)
0.03
0.03


 


325




486.2 (M + 1)
0.03
0.029


 


326




474.2 (M + 1)
0.03
0.022


 


327




432.2 (M + 1)
0.03
0.021


 


328




533.2 (M + 1)
0.34
0.229


 


329




337.2 (M + 1)
0.15
0.116


 


330




341.2 (M + 1) 1H NMR: (300 Hz, DMSO-d6) δ 7.47 (s, 1H), 7.32 (1H, d, J = 4.5 Hz), 7.17 (1H, d, J = 3.6 Hz), 7.05 (s, 1H), 3.91 (2H, d,  J = 7.5 Hz), 6.44 (2H, d,  J = 7.8 Hz), 3.87 (s, 2H), 3.55 (s, 2H), 3.02 (s, 2H), 2.15 (s, 3H)
4.47



 


331




345.1 (M + 1) 1H NMR (300 MHz, CDCl3) δ 7.76-7.72 (m, 2H) 7.08-6.99 (m, 3H) 6.50- 6.43 (m, H) 6.38-6.35 (m, 1H) 5.26 (s, H) 4.17 (s, 2H) 3.73-3.69 (m, 2H) 3.27-3.23 (m, 2H) 2.05 (s, 2H).
0.14



 


332




570.3 (M + 1)
1.04



 


333




563.2 (M + 1)
1.11



 


334




509.2 (M + 1)
0.05



 


335




565.2 (M + 1)
2.3



 


336




495.2 (M + 1)
0.04



 


337




486.2 (M + 1)
>10



 


338




458.2 (M + 1)
0.19



 


339




500.2 (M + 1)
0.52



 


340




458.2 (M + 1)
0.2



 


341




522.3 (M + 1)
0.01



 


342




506.2 (M + 1)
5.24



 


343




506.2 (M + 1)
7.5



 


344




601.2 (M + 1)
0.21



 


345




587.2 (M + 1)




 


346




585.1 (M + 1)
>8.8



 


347




520.3 (M + 1)
5.92



 


348




499.9 (M + 1)
0.05



 


349




481.6 (M + 1)
7.48



 


350




409.2 (M + 1)
0.66



 


351




439.2 (M + 1)
1.24



 


352




394.2 (M + 1)
0.01



 


353




437.2 (M + 1)
0.21



 


354




306.2 (M + 1) H-NMR (300 MHz, CDCl3): 2.29 (s, 3H), 3.03 (m, 2H), 3.43 (s, 1H), 3.81 (m, 2H), 3.90 (s, 2H), 5.57 (s, 1H), 6.60-6.63 (2H, d, J = 8.4 Hz), 7.06-7.09 (2H, d, J = 8.1 Hz), 7.79 (m, 2H), 8.44-8.46 (m, 2H)
6.32
0.564


 


355




600 (M + 1)
2.81
2.266


 


356




459.2 (M + 1)
1.26
0.872


 


357




532.3 (M + 1)
7.49
4.712


 


358




475.2 (M + 1)
0.13
0.049


 


359




511.2 (M + 1)
0.14
0.108


 


360




461.2 (M + 1)
0.03
0.015


 


361




490.3 (M + 1)
2.35
1.141


 


362




470.6 (M + 1)
0.81
0.203


 


363




532.2 (M + 1)
1.75
1.133


 


364




514.6 (M + 1)
4.95
3.742


 


365




562.1 (M + 1)
0.61
0.26


 


366




462.2 (M + 1)
3.47
1.824


 


367




474.2 (M + 1)
0.19
0.148


 


368




562.2 (M + 1)
0.52
0.286


 


369




529.2 (M + 1)
0.11
0.084


 


370




516.1 (M + 1)
4.35
8.345


 


371




546.6 (M + 1)
1.52
1.283


 


372




488.2 (M + 1)
0.69
0.554


 


373




474.3 (M + 1)
0.43
0.32


 


374




484.3 (M + 1)
0.59
0.248


 


375




480.2 (M + 1)
1.13
0.679


 


376




436.2 (M + 1)
0.06
0.079


 


377




450.3 (M + 1)

0.574


 


378




450.3 (M + 1)
0.06
0.063


 


379




426.2 (M + 1)
0.06
0.05


 


380




498.3 (M + 1)
1.13
1.789


 


381




392.2 (M + 1)
1.97
1.798


 


382




363.2 (M + 1)
1.05
1.039


 


383




396.2 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.62-7.59 (m, 2H); 7.14- 7.04 (m, 2H); 6.85 (d, J = 2.4 Hz, 1H); 6.65- 6.5 (dd, J = 2.7 Hz, J = 8.4 Hz, 1H); 4.0-3.98 (m, 4H); 2.16 (s, 3H); 2.00 (s, 6H); 1.64 (s, 6H).
0.05
0.032


 


384




484.3 (M + 1)
0.47
0.889


 


385




398.2 (M + 1)
0.02
0.02


 


386




498.3 (M + 1)
2.62
3.028


 


387




398.2 (M + 1)
0.11
0.08


 


388




498.3 (M + 1)
3.22
1.772


 


389




450.3 (M + 1)
0.06
0.051


 


390




473.3 (M + 1)
0.03
0.028


 


391




441.2 (M + 1)
0.01
0.007


 


392




436.3 (M + 1)
0.03
0.039


 


393




446.2 (M + 1)
0.02



 


394




474.0 (M + 1)
0.05
0.043


 


395




426.2 (M + 1)
0.44
0.246


 


396




440.2 (M + 1)
0.03
0.022


 


397




424.2 (M + 1)
2.45
1.673


 


398




391.2 (M + 1)
2.73
2.685


 


399




436.2 (M + 1)
0.22
0.196


 


400




518.2 (M + 1)
0.18
0.105


 


401




434.2 (M + 1)
0.02
0.012


 


402




484.3 (M + 1)
0.12
0.122


 


403




484.3 (M + 1)
0.51
0.543


 


404




420.2 (M + 1)
0.02
0.012


 


405




524.2 (M + 1)
0.02
0.012


 


406




412.2 (M + 1)
0.06
0.04


 


407




484.3 (M + 1)
0.71
0.523


 


408




426.2 (M + 1)
0.93
0.908


 


409




408.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.79- 7.69 (m, 2H), 7.21 (t, J = 8.4 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H), 6.76 (d, J = 8.2 Hz, 2H), 4.11 (s, 2H), 3.88 (m, 4H), 2.22 (s, 3H), 2.12 (s, 6H).
0.01
0.006


 


410




463.3 (M + 1)
0.06
0.037


 


411




378.2 (M + 1)
0.14
0.106


 


412




412.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.61- 7.57 (m, 2H), 6.94 (2H, J =  8.8 Hz, t), 6.81 (2H, J = 8.8 Hz, t), 6.47 (m, 2H), 3.72 (m, 2H), 3.58 (m, 2H), 3.42 (m, 2H), 1.85 (s, 6H). Elemental Analysis: (compound + 0.65 H2O): C, 62.44; N, 16.55; H, 5.79, (calculated). C = 62.54/62.44; N = 16.35/16.29; H = 5.52/5.61 (experimental)
0.01
0.006


 


413




389.1 (M + 1) 1H NMR: (300 Hz, DMSO-d6) δ 7.59 (m, 2H), 7.35 (t, J = 6.6 Hz, 1H), 7.12 (t, J = 6.6, 2H), 6.68 (d, J = 8.7 Hz, 1H), 6.42 (d, J = 6.9 Hz, 1H), 3.88 (d, J = 1.5 Hz, 2H), 3.68-3.61 (m, 2H), 3.57- 3.50 (m, 2H), 3.02 (t, J = 4.2 Hz, 2H), 1.04 (t, J = 5.4 Hz, 3H)
0.18
0.131


 


414




436.2 (M + 1)
0.16
0.156


 


415




351.2 (M + 1)
0.01
0.013


 


416




371.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.77- 7.73 (m, 2H); 7.25-7.18 (m, 4H); 6.84-6.82 (m, 2H); 4.38 (m, 2H); 3.95 (m, 2H); 2.11 (s, 6H).
0.01
0.016


 


417




428.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.75- 7.71 (m, 2H), 7.13-7.1 (m, 2H), 6.59 (t J =  8.8 Hz, 2H), 6.58 (d, J = 8.8 Hz, 2H), 3.80 (m, 2H), 3.65 (m, 2H), 3.31 (m, 2H), 1.95 (s, 6H). Elemental Analysis: (compound +  0.33 H2O): Elemental Analysis: C, 60.11; N, 15.93; H, 5.57; (calculated). % C, 60.93/60.79; % N, 15.99/16.08; % H, 5.54/5.40 (experimental)
0.01
0.006


 


418




398.2 (M + 1)
0.09
0.146


 


419




446.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.59- 7.55 (m, 2H); 7.20-7.13 (m, 3H); 6.60 (dd, J = 10.8 Hz, J = 11.2 Hz, 1H); 6.53 (dd, J = 0.8 Hz, J = 2.4 Hz, 1H); 4.0 (m, 4H); 3.78 (m, 2H); 2.00 (s, 6H).
0.03
0.024


 


420




389.8 (M + 1)
0.02
0.028


 


421




430.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.73- 7.69 (m, 2H); 7.07-6.99 (m, 3H); 6.46-6.40 (m, 1H); 6.34- 6.32 (m, 1H); 3.78 (m, 2H), 3.62 (m, 2H), 3.5 (m, 2H); 1.98 (s, 6H); 1.48 (s, 6H).
0.003
0.005


 


422




373.2 (M + 1)
0.01
0.021


 


423




446.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.70- 7.66 (m, 2H); 7.18-7.14 (m, 3H); 7.07 (t, J = 9.2 Hz, 1H); 6.8-6.78 (m, 1H); 6.64-6.60 (M, 1H); 2.04 (s, 6H).
0.01
0.009


 


424




389.1 (M + 1)
0.02
0.03


 


425




419.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.68- 7.65 (m, 2H); 7.54 (d, J =8.8 Hz, 2H); 7.17 (t, J = 8.8 Hz, 2H); 6.83 (d, J = 8.4 Hz, 2H); 4.07 (s, 2H); 4.03 (s, 2h); 3.82 (m, 2H); 2.06 (s, 6H).
0.01
0.012


 


426




362.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) 7.69 (m, 2H); 7.51 (d, J = 8.4 Hz, 2H);. 7.07 (t, J = 8.8 Hz, 2H); 6.73 (d, J =  8.8 Hz, 2H); 4.01 (m, 2H); 3.78 (m, 2H); 1.86 (s, 6H).
0.18
0.271


 


427




460.2 (M + 1)
0.21
0.436


 


428




440.2 (M + 1)
0.17
0.242


 


429




470.2 (M + 1)
0.02
0.036


 


430




445.2 (M + 1)
0.01
0.019


 


431




499.2 (M + 1)
0.07
0.08


 


432




506.2 (M + 1)
0.06
0.067


 


433




528.2 (M + 1)
0.04
0.049


 


434




444.2 (M + 1)
0.02
0.019


 


435




416.2 (M + 1)
0.05
0.098


 


436




496.3 (M + 1)
0.03
0.052


 


437




442.2 (M + 1)
0.02
0.028


 


438




456.3 (M + 1)
0.02
0.023


 


439




458.3 (M + 1)
0.03
0.04


 


440




445.2 (M + 1)
0.02
0.028


 


441




428.2 (M + 1)
0.06
0.081


 


442




458.2 (M + 1)
0.02
0.033


 


443




510.2 (M + 1)
0.05
0.055


 


444




403.2 (M + 1) 1H NMR: (300 MHz, CDCl3) δ 7.60- 7.55 (m, 2H), 7.28-7.21 (m, 1H), 7.03- 6.97 (m, 2H), 6.58-6.53 (m, 1H), 6.44- 6.39 (m, 1H), 4.29 (s, 2H), 4.19-4.10 (m, 1H), 3.79 (br, 1H), 3.55 (br, 1H), 3.30- 3.26 (br, 2H), 1.18-1.16 (br, 3H), 1.01-0.99 (br, 3H).
7.22
5.965


 


445




369.2 (M + 1)
2.6
3.272


 


446




355.2 (M + 1) H-NMR: (DMSO, 300 Hz): δ 7.67-7.63 (m, 2H), 7.23- 7.16 (m, 1H), 7.03-6.97 (m, 2H), 6.57- 6.41 (m, 3H), 4.22 (s, 1H), 3.69-3.55 (m, 4H), 3.24 (t, J = 4.8 Hz, 2H), 2.61 (s, 2H), 1.17 (t, J = 7.2 Hz, 3H)
0.31
0.243


 


447




361.0 (M + 1) 1H NMR: (300 MHz, CDCl3) δ 7.76-7.71 (m, 2H), 7.25-7.19 (m, 1H), 7.05- 6.99 (m, 2H), 6.48-6.41 (m, 2H), 5.44 (s, H), 4.17 (s, 2H), 3.73-3.70 (m, 2H), 3.27- 3.23 (m, 2H)
0.23



 


448




414.2 (M + 1)
0.02
0.022


 


449




442.2 (M + 1)
0.03
0.026


 


450




440.2 (M + 1)
0.02
0.015


 


451




454.2 (M + 1)
0.03
0.019


 


452




469.0 (M + 1)
0.02
0.019


 


453




456.2 (M + 1)
0.02
0.021


 


454




456.2 (M + 1)
0.02
0.008


 


455




443.0 (M + 1)
0.01
0.008


 


456




443.0 (M + 1)
0.02
0.015


 


457




494.2 (M + 1)
0.02
0.011


 


458




508.2 (M + 1)
0.02
0.017


 


459




504.2 (M + 1)
0.04
0.024


 


460




526.2 (M + 1)
0.04
0.033


 


461




497.2 (M + 1)
0.03
0.022


 


462




426.2 (M + 1)
0.05
0.037


 


463




456.2 (M + 1)
0.04
0.024


 


464




426.2 (M + 1)
0.03
0.024


 


465




424.2 (M + 1)
0.0019
0.002


 


466




438.2 (M + 1)
0.03



 


467




452.2 (M + 1)
0.02
0.016


 


468




440.2 (M + 1)
0.03
0.02


 


469




440.2 (M + 1)
0.02
0.016


 


470




427.1 (M + 1)
0.01
0.012


 


471




427.1 (M + 1)
0.03
0.03


 


472




478.2 (M + 1)
0.05
0.037


 


473




492.2 (M + 1)
0.03
0.021


 


474




488.2 (M + 1)
0.13
0.088


 


475




510.0 (M + 1)
0.04
0.03


 


476




480.9 (M + 1)
0.04
0.027


 


477




410.0 (M + 1)
0.07
0.055


 


478




440.0 (M + 1)
0.06
0.039


 


479




448.2 (M + 1)
0.02
0.012


 


480




436.2 (M + 1)
0.03
0.022


 


481




436.2 (M + 1)
0.02
0.014


 


482




474.2 (M + 1)
0.02
0.009


 


483




488.2 (M + 1)
0.05
0.025


 


484




484.3 (M + 1)
0.04
0.023


 


485




506.2 (M + 1)
0.03
0.023


 


486




477.0 (M + 1)
0.03
0.016


 


487




458 (M + 1)
0.04
0.031


 


488




472.2 (M + 1)
0.02
0.013


 


489




461.2 (M + 1)
0.01
0.009


 


490




512.2 (M + 1)
0.05
0.033


 


491




458 (M + 1)
0.08
0.055


 


492




446.2 (M + 1)
0.05



 


493




355.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.62- 7.58 (m, 2H); 7.12-7.08 (m, 2H); 6.68-6.63 (m, 2H); 6.67 (m, 2H); 4.16 (m, 2H); 3.78 (m, 2H); 1.92 (s, 6H).
0.004
0.005


 


494




337.2 (M + 1)
2.82
2.141


 


495




426.0 (M + 1)
0.09
0.039


 


496




442.2 (M + 1)
0.03
0.008


 


497




357.1 (M + 1)
8.0
5.825


 


498




357.1 (M + 1)
6.34
6.738


 


499




408.2 (M + 1)
0.01
0.006


 


500




419.0 (M + 1)
1.56
1.1


 


501




369.2 (M + 1)
0.4
0.305


 


502




502.3 (M + 1)
1.39
1.373


 


503




450.3 (M + 1)
0.12
0.095


 


504




424.0 (M + 1)
0.09
0.093


 


505




424.2 (M + 1)
0.14
0.116


 


506




420.3 (M + 1)
0.19
0.198


 


507




365.2 (M + 1)
0.14
0.136


 


508




385.0 (M + 1)
0.13
0.126


 


509




387.2 (M + 1)
0.13
0.134


 


510




387.2 (M + 1)
2.05
1.564


 


511




403.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.74- 7.70 (m, 2H); 7.21 (t, J = 8.4 Hz, 1H), 7.08 (m, 2H); 6.49- 6.40 (m, 2H); 4.43 (s, 2H); 1.72 (s, 6H).
0.04
0.065


 


512




369.2 (M + 1)
0.19
0.165


 


513




403.0 (M + 1)
0.17
0.195


 


514




355.1 (M + 1)
0.03
0.024


 


515




405.1 (M + 1)
0.04
0.034


 


516




451.2 (M + 1)
0.03
0.026


 


517




394.1 (M + 1)
0.05
0.051


 


518




422.2 (M + 1)
4.98
2.888


 


519




414.2 (M + 1)
0.84
0.59


 


520




414.2 (M + 1)
0.16
0.158


 


521




442.2 (M + 1)
5.0
3.026


 


522




437.0 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.61- 7.57 (m, 2H); 7.15-7.07 (m, 4H); 7.02- 7.01 (m, 1H); 4.0 (m, 4H); 3.81 (m, 2H); 2.01 (s, 6H).
0.0017
0.002


 


523




399.0 (M + 1)
13.11
11.649


 


524




380.2 (M + 1)
0.04
0.057


 


525




433.5 (M + 1)
0.01
0.013


 


526




395.0 (M + 1)
1.12
0.974


 


527




376.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.61- 7.57 (m, 2H); 7.15-7.07 (m, 4H); 7.02- 7.01 (m, 1H); 4.0 (m, 4H); 3.81 (m, 2H); 2.01 (s, 6H).
0.004
0.006


 


528




501.2 (M + 1)
0.15
0.121


 


529




436.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.78- 7.75 (m, 2H); 7.06-6.97 (m, 4H); 6.56 (d, J = 8.4 Hz, 2H), 5.16 (s, NH); 4.33 (t, J = 4.8 Hz, 2H), 3.74 (t, J = 4.8 Hz, 2H), 4.16 (m, 2H); 2.29 (s, 3H); 1.95 (s, 6H); 1.45 (s, 6H).
0.002
0.004


 


530




482.2 (M + 1)
1.23
6.422


 


531




400.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.67- 7.63 (m, 2H); 7.21-7.17 (t, J = 8.8 Hz, 2H), 4.15 (m, 2H); 3.79 (m, 2H); 2.72 (m, 1H); 1.95 (s, 6H); 1.72 (m, 2H); 1.58 (m, 2H); 1.46 (m, 1H); 1.1-1.05 (m, 5H).
0.04
0.057


 


532




442.2 (M + 1)
0.02
0.009


 


533




426.2 (M + 1)
0.03
0.022


 


534




453.2 (M + 1)
0.04
0.019


 


535




390.2 (M + 1)
2.72
2.351


 


536




397.2 (M + 1)
6.4
5.93


 


537




394.2 (M + 1)
11.91
8.342


 


538




407.2 (M + 1)
7.67
8.065


 


539




393.2 (M + 1)
3.06
3.123


 


540




375.2 (M + 1) 1H-NMR: (300 Hz, CD3OD) δ 7.74- 7.69 (m, 2H), 7.42 (s, 1H), 7.13-7.07 (m, 2H), 4.84 (s, 2H), 4.19- 3.97 (6H, m), 1.47 (9H, s)
8.42
9.807


 


541




369.2 (M + 1)
0.01
0.01


 


542




369.2 (M + 1)
0.002
0.003


 


543




405.2 (M + 1)
0.17
0.305


 


544




383.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.65- 7.62 (m, 2H); 6.95-6.91 (m, 1H); 6.72 (t, J = 9.2 Hz, 1H), 6.28-6.25 (m, 1H); 4.30 (s, 2H) 2.04 (s, 3H); 1.81 (s, 6H).
0.02
0.037


 


545




382.2 (M + 1)
3.38
5.618


 


546




399.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.60- 7.56 (m, 2H); 7.09-7.05 (m, 2H); 6.99 (d, J = 8.0 Hz, 1H), 6.67 (d, J = 2.4 Hz, 2H); 6.46 (dd, J =  2.4 Hz, J = 8.0 Hz, 1H); 4.44 (s, 2H) 2.13 (s, 3H); 1.71 (s, 6H).
0.03
0.052


 


547




366.2 (M + 1)
1.82
4.662


 


548




410.0 (M + 1)
2.63
5.549


 


549




399.1 (M + 1)
1.7
3.261


 


550




417.1 (M + 1)
2.56
3.6


 


551




421.0 (M + 1)
0.04
0.098


 


552




487.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.72- 7.67 (m, 4H); 7.2 (t, J = 8.8 Hz, 2H); 6.8 (d, J = 8.4 Hz, 2H), 4.01 (m, 4H), 3.86 (t, J = 4.4 Hz, 2H); 2.88 (s, 3H); 2.1 (s, 6H).
2.52
4.482


 


553




451.2 (M + 1)
2.37
4.658


 


554




448.0 (M + 1)
0.0
0.007


 


555




391.2 (M + 1)
0.01
0.016


 


556




385.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.72- 7.69 (m, 2H); 7.19-7.15 (4H, m); 6.67 (2H, J = 9.2 Hz, d); 4.64 (s, 2H); 4.64 (s, 2H); 3.99 (s, 2H), 2.91 (s, 2H), 1.43 (s, 6H).
0.06
0.075


 


557




428.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.74 (m, 2H); 7.19- 7.15 (m, 2H); 6.69 (d, J = 8.8 Hz, 2H); 4.88 (s, 2H); 4.08 (s, 2H); 3.99 (s, 2H), 2.91 (s, 2H), 1.54 (s, 6H).
0.02
0.02


 


558




371.1 (M + 1) 1H-NMR: (CDCl3, 400 Hz) δ 7.75- 7.71 (m, 2H); 7.18 (d, J = 9.2 Hz, 2H); 6.99 (t, J = 8.8 Hz, 2H); 6.56 (d, J = 8.8 Hz, 2H); 5.37 (s, NH); 4.15 (s, 2H); 3.49 (s, NH); 3.42 (s, 2H); 1.22 (s, 6H).
0.06
0.089


 


559




389.0 (M + 1)
0.53
0.642


 


560




369.2 (M + 1)
3.61
5.219


 


561




386.2 (M + 1)
7.17
4.403


 


562




417.2 (M + 1)
4.82
6.293


 


563




371.0 (M + 1)
0.31
0.445


 


564




389.0 (M + 1)
0.25
0.359


 


565




371.0 (M + 1)
0.07
0.105


 


566




402.2 (M + 1)
5.48
4.463


 


567




429.2 (M + 1)
6.46
8.458


 


568




449.0 (M + 1)
>8.04
>11.3


 


569




463.3 (M + 1)
9.27
7.916


 


570




472.2 (M + 1)
5.68
5.562


 


571




492.1 (M + 1)
6.2
7.48


 


572




435.1 (M + 1)
11.18
8.73


 


573




408.2 (M + 1)
0.04
0.055


 


574




412.1 (M + 1)
0.08
0.111


 


575




430.2 (M + 1)
0.08
0.081


 


576




446.2 (M + 1)
0.2
0.234


 


577




437.1 (M + 1)
0.63
0.611


 


578




351.2 (M + 1)
0.25
0.339


 


579




355.2 (M + 1)
0.18
0.146


 


580




373.2 (M + 1)
0.15
0.169


 


581




380.2 (M + 1)
0.65
0.668


 


582




471.1 (M + 1)
5.56
5.919


 


583




440.0 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.66 (dd, J = 5.2 Hz, J =  9.2 Hz, 2H): 7.11 (t, J = 8.8 Hz, 2H); 6.81 (t, J = 8.8 Hz, 2H); 6.72- 6.68 (m, 2H); 4.04-3.99 (m, 4H); 2.01 (s, 6H); 1.66 (s, 6H).
0.01
0.009


 


584




456.2 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.60-7.59 (m, 2H); 7.16- 7.09 (m, 4H); 6.7 (d, J = 8.4 Hz, 2H); 4.01 (m, 4H); 2.01 (s, 6H); 1.65 (s, 6H).
0.02
0.021


 


585




458.1 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.63-7.60 (m, 2H); 7.14 (t, J = 8.4 Hz, 2H); 7.01 (dd, J = 8.8 Hz, J = 18.8 Hz, 1H); 6.68-6.63 (m, 1H); 6.5 (m, 1H); 4.03 (m, 2H); 4.01 (m, 2H); 2.01 (s, 6H); 1.66 (s, 6H).
0.01
0.007


 


586




474.2 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.63-7.59 (m, 2H); 7.13 (t, J = 8.8 Hz, 2H); 6.97 (t, J = 9.2 Hz, 1H); 6.84 (t, J = 3.6 Hz, 1H); 4.03 (m, 2H); 4.01 (m, 2H); 2.01 (s, 6H); 1.66 (s, 6H).
0.01
0.007


 


587




491.2 (M + 1)
0.01
0.012


 


588




454.2 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.73-7.70 (m, 2H); 7.21 (t, J = 8.8 Hz, 2H); 6.87 (t, J = 8.8 Hz, 1H); 6.68 (m, 1H); 4.12 (m, 4H); 2.17 (s, 3H); 2.15 (s, 6H); 1.76 (s, 6H).
0.01
0.004


 


589




470.2 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.62-7.59 (m, 2H); 7.16- 7.06 (m, 3H); 6.66 (d, J = 2.4 Hz, 1H); 6.50 (dd, J = 2.8 Hz, J = 8.4 Hz, 1H); 3.99 (m, 4H); 2.17 (s, 3H); 2.01 (s, 6H); 1.65 (s, 6H).
0.01
0.006


 


590




461.2 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.32-7.59 (m, 2H); 7.14 (m, 3H); 6.97 (m, 2H); 4.01 (m, 4H); 2.29 (s, 3H); 2.02 (s, 6H); 1.81 (s, 6H).
0.03
0.018


 


591




481.0 (M + 1)
0.06
0.046


 


592`




451.2 (M + 1)
6.01
5.256


 


593




436.2 (M + 1)
5.06
3.937


 


594




408.2 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.58- 7.40 (m, 3H); 7.13 (t, J = 8.4 Hz, 1H); 6.99 (m, 2H); 6.61 (d, J = 8.0 Hz, 2H); 5.17-5.14 (m, 2H); 4.28- 3.92 (m, 4H); 2.20 (s, 3H), 1.70 (s, 3H), 1.65 (s, 3H).
0.02
0.032


 


595




460.2 (M + 1)
0.34
0.485


 


596




432.2 (M + 1)
0.03
0.029


 


597




432.2 (M + 1)
0.03
0.024


 


598




383.2 (M + 1)
0.04
0.074


 


599




499.3 (M + 1)
0.12
0.134


 


600




412.2 (M + 1) 1H-NMR (400 MHz, MeOH- d4) δ 7.76 (dd, J = 5.2 Hz, J =  8.8 Hz, 2H); 7.29 (t, J = 8.4 Hz, 2H); 4.26 (s, 2H); 4.16 (s, 2H); 4.00 (s, 2H); 3.76 (s, 3H); 1.92 (s, 6H); 2.14 (s, 6H).
0.07
0.05


 


601




412.2 (M + 1)
3.96
4.117


 


602




460.2 (M + 1)
0.17
0.204


 


603




383.2 (M + 1)
0.05
0.073


 


604




399.2 (M + 1)
0.04
0.049


 


605




403.0 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.43 (td, J = 8.0 Hz, J = 1.0 Hz 1H); 7.38-7.34 (m, 1H); 7.24- 7.18 (m, 1H); 7.11 (t, J =  8.40 Hz, 1H); 6.87-6.8 (m, 1 H); 6.37 (dd, J = 11.2 Hz, J =  2.40 Hz 1H); 6.33-6.30 (m, 1H); 4.33 (s, 2H), 1.62 ( (s, 6H). 
0.04
0.057


 


606




369.1 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.63- 7.59 (m, 2H); 7.11 (t, J =  8.40 Hz, 2H); 6.85 (t, J =  8.40 Hz, 2H); 6.7-6.68 (m, 2H); 4.3 (m, 2H); 3.87 (m, 2H); 3.01 (s, 3H); 1.97 (s, 6H).
0.02
0.028


 


607




385.2 (M + 1)
0.03
0.048


 


608




385.1 (M + 1)
6.91
5.562


 


609




403.2 (M + 1)
7.02
4.929


 


610




399.1 (M + 1)
6.25
4.903


 


611




387.1 (M + 1)
7.67
5.762


 


612




390.2 (M + 1)
6.9
6.082


 


613




523.2 (M + 1)
6.27
5.711


 


614




519.2 (M + 1)
5.02
4.524


 


615




417.0 (M + 1)
6.41
5.609


 


616




413.2 (M + 1)
5.72
4.562


 


617




397.2 (M + 1)
6.33
6.878


 


618




403.8 (M + 1)
2.13
2.887


 


619




399.2 (M + 1)
0.57
0.713


 


620




428.0 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.48- 7.41 (m, 3H); 7.16-7.14 (m, 3H); 6.71 (d, J = 8.4 Hz, 2H); 5.17-5.14 (m, 2H); 4.28- 3.92 (m, 4H); 1.71 (s, 3H), 1.66 (s, 3H).
0.04
0.041


 


621




412.2 (M + 1)
0.04
0.045


 


622




430.2 (M + 1)
0.1
0.121


 


623




446.2 (M + 1)
0.03
0.032


 


624




446.2 (M + 1)
0.1
0.167


 


625




426.2 (M + 1)
0.17
0.194


 


626




442.0 (M + 1) 1H-NMR: (MeOH-d4, 400 Hz) δ 7.47- 7.39 (m, 2H); 7.19-7.11 (m, 2H); 6.67 (s, 1H); 6.52 (d, J = 8.0 Hz, 1H); 5.15 (s, 2H); 4.27-3.91 (m, 2H); 2.24 (s, 3H), 1.71 (s, 3H), 1.65 (s, 3H).
0.02
0.017


 


627




403.2 (M + 1)
0.17
0.194


 


628




426.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.69-7.73 (m, 2H), 7.18 (t, J = 8.8 Hz, 2H), 6.87 (t, J = 8.8 Hz, 2H), 6.62-6.63 (m, 1H), 6.51- 6.55 (m, 1H), 5.12 (s, 2H), 4.21 (t, J =  4.8 Hz, 2H), 4.02 (t, J = 4.8 Hz, 2H), 2.17 (s, 3H), 1.75 (s, 6H)
0.033
0.04


 


629




442.1 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.70-7.73 (m, 2H), 7.22 (t, J = 8.0 Hz, 2H), 7.17 (d, J =  7.2 Hz, 1H), 6.77 (s, 1H), 6.62 (d, J =  6.0 Hz, 1H), 5.20 (s, 2H), 4.27 (s, 2H), 4.08 (s, 2H), 2.27 (s, 3H), 1.78 (s, 6H)
0.017
0.023


 


630




433.3 (M + 1)
0.035
0.085


 


631




426.3 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.72-7.76 (m, 2H), 7.22 (t, J = 8.8 Hz, 2H), 7.06 (t, J = 8.8 Hz, 1H), 8.56 (s, 1H), 6.53-6.54 (m, 1H), 5.20 (s, 2H), 4.27 (t, J = 4.8 Hz, 2H), 4.09 (t, J =  4.8 Hz, 2H), 2.13 (s, 3H), 1.79 (s, 6H)
0.049
0.062


 


632




442.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.71-7.74 (m, 2H), 7.22 (t, J = 8.8 Hz, 2H), 7.11 (d, J = 8.4 Hz, 1H), 6.85 (d, J = 2.4 Hz, 1H),  6.67 (dd, J =  2.4, 8.4 Hz, 1H), 5.20 (s, 2H), 4.27 (t, J = 4.2 Hz, 2H), 4.09 (t, J =  4.2 Hz, 2H), 2.24 (s, 3H), 1.78 (s, 6H) 
0.015
0.016


 


633




496.1 (M + 1)
0.528
0.331


 


634




480.1 (M + 1)
0.467
0.447


 


635




487.1 (M + 1)
0.94
1.758


 


636




437.2 (M + 1)
0.21
0.183


 


637




422.3 (M + 1)
0.027
0.026


 


638




408.3 (M + 1)
0.065
0.068


 


639




428.2 (M + 1)
0.082
0.093


 


640




478.2 (M + 1)
3.95
4.51


 


641




422.2 (M + 1)
0.799
1.285


 


642




460.2 (M + 1)
2.01
2.497


 


643




478.2 (M + 1)
2.798
2.171


 


644




462.1 (M + 1)
0.31
0.49


 


645




426.1 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.75-7.78 (m, 2H), 6.95- 7.01 (m, 3H), 6.44-6.50 (m, 1H), 6.32- 6.36 (m, 1H), 4.19 (dd, J = 1.6, 6.8 Hz, 2H), 4.00 (dd, J = 1.6, 6.8 Hz, 2H), 1.47 (s, 6H)
5.13
7.6


 


646




428.1 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.59-7.63 (m, 2H), 7.09 (t, J = 6.4 Hz, 2H), 6.95-7.02 (m, 1H), 6.46- 6.52 (m, 1H), 6.34-6.38 (m, 1H), 5.92 (s, 1H), 4.33 (dd, J = 4.4, 14 Hz, 1H), 3.96 (dd, J = 4.8, 13.2 Hz, 1H), 3.70-3.78 (m, 1H), 3.46- 3.54 (m, 1H), 1.73 (s, 3H), 1.36 (s, 3H)
5.68
6.13


 


647




470.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.72-7.76 (m, 2H), 7.50- 7.54 (m, 4H),  7.39 (t, J = 8.0 Hz, 2H), 7.27 (t, J = 7.2 Hz, 1H), 7.20 (t, J = 8.8 Hz, 2H), 6.82 (d, J = 8.4 Hz, 2H), 4.07-4.10 (m, 4H), 3.84 (t, J = 4.8 Hz, 2H), 2.09 (s, 6H)
0.279
0.25


 


648




422.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.76-7.71 (m, 2H), 7.21 (t, J = 8.8 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 6.67 (d, J = 8.4 Hz, 2H), 4.05-4.08 (m, 4H), 3.83- 3.85 (m, 2H), 2.55 (q, J = 7.6 Hz, 2H), 2.09 (s, 6H), 1.18 (t, J = 7.6 Hz, 3H)
0.009
0.008


 


649




478.1 (M + 1)
0.024
0.018


 


650




478.1 (M + 1)
0.012
0.009


 


651




428.1 (M + 1)
0.008
0.005


 


652




462.1 (M + 1)
0.019
0.012


 


653




419.1 (M + 1)
0.006
0.009


 


654




422.2 (M + 1)
0.005
0.006


 


655




487.1 (M + 1)
0.017
0.02


 


656




422.1 (M + 1)
0.006
0.007


 


657




480.1 (M + 1)
0.618
1.086


 


658




496.0 (M + 1)
0.005
0.006


 


659




442.6 (M + 1)
4.39
5.28


 


660




436.1 (M + 1)
0.003
0.006


 


661




476.2 (M + 1)
0.339
0.52


 


662




468.1 (M + 1)
0.038
0.033


 


663




456.2 (M + 1)
1.062
1.658


 


664




414.2 (M + 1)
3.69
4.08


 


665




414.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.71-7.74 (m, 2H), 7.29 (t, J = 8.8 Hz, 2H), 4.20 (t, J = 4.8 Hz, 2H), 4.12 (s, 2H), 3.86 (t, J = 4.8 Hz, 2H), 3.02-3.09 (m, 1H), 2.02 (s, 6H), 1.79- 1.86 (m, 2H), 1.57-1.63 (m, 2H), 1.48- 1.52 (m, 4H), 1.39-1.46 (m, 2H), 1.21- 1.30 (m, 2H)
0.102
0.069


 


666




442.2 (M + 1)
>10
4.97


 


667




412.2 (M + 1)
0.104
0.082


 


668




415.7 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.59-7.63 (m, 2H), 7.32 (t, J = 8.8 Hz, 2H), 4.25 (d, J = 4.8 Hz, 2H), 4.13 (s, 2H), 3.97-4.04 (m, 1H), 3.88 (d, J = 4.8 Hz, 2H), 3.49- 3.54 (m, 1H), 3.41-3.47 (m, 2H), 3.25- 3.30 (m, 1H), 2.92 (s, 6H), 2.45-2.53 (m, 1H), 2.23- 2.28 (m, 1H), 2.01 (s, 6H)
3.43
>10


 


669




469.7 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.47-7.51 (m, 2H), 7.22 (t, J = 8.8 Hz, 2H), 4.13 (t, J = 4.4 Hz, 2H), 4.03 (s, 2H), 3.42 (d, J = 11.6 Hz, 2H), 3.15 (d, J = 12.4 Hz, 2H), 2.90 (dd, J = 10.8, 22.4 Hz, 4H), 2.00- 2.03 (m, 2H), 1.90 (s, 6H), 1.68-1.87 (m, 6H), 1.37- 1.47 (m, 1H
3.98
>10


 


670




386.6 (M + 1)
0.402
0.711


 


671




372.3 (M + 1)
1.286
1.087


 


672




402.3 (M + 1)
9.84
7.14


 


673





8.87
>8.72


 


674





6.28
6.31


 


675




446.5 (M + 1)
0.014
0.021


 


676




415.7 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.59-7.63 (m, 2H), 7.32 (t, J = 8.8 Hz, 2H), 4.25 (d, J = 4.8 Hz, 2H), 4.13 (s, 2H), 3.97-4.04 (m, 1H), 3.88 (d, J = 4.8 Hz, 2H), 3.49- 3.54 (m, 1H), 3.41-3.47 (m, 2H), 3.25- 3.30 (m, 1H), 2.92 (s, 6H), 2.45-2.53 (m, 1H), 2.23- 2.28 (m, 1H), 2.01 (s, 6H)
0.032
0.031


 


677




469.7 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.47-7.51 (m, 2H), 7.22 (t, J = 8.8 Hz, 2H), 4.13 (t, J = 4.4 Hz, 2H), 4.03 (s, 2H), 3.42 (d, J = 11.6 Hz, 2H), 3.15 (d, J = 12.4 Hz, 2H), 2.90 (dd, J = 10.8, 22.4 Hz, 4H), 2.00- 2.03 (m, 2H), 1.90 (s, 6H), 1.68-1.87 (m, 6H), 1.37- 1.47 (m, 1H
0.08
0.076


 


678




415.7 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.59-7.63 (m, 2H), 7.32 (t, J = 8.8 Hz, 2H), 4.25 (d, J = 4.8 Hz, 2H), 4.13 (s, 2H), 3.97-4.04 (m, 1H), 3.88 (d, J = 4.8 Hz, 2H), 3.49- 3.54 (m, 1H), 3.41-3.47 (m, 2H), 3.25- 3.30 (m, 1H), 2.92 (s, 6H), 2.45-2.53 (m, 1H), 2.23- 2.28 (m, 1H), 2.01 (s, 6H)
0.053
0.047


 


679




469.7 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.47-7.51 (m, 2H), 7.22 (t, J = 8.8 Hz, 2H), 4.13 (t, J = 4.4 Hz, 2H), 4.03 (s, 2H), 3.42 (d, J = 11.6 Hz, 2H), 3.15 (d, J = 12.4 Hz, 2H), 2.90 (dd, J = 10.8, 22.4 Hz, 4H), 2.00- 2.03 (m, 2H), 1.90 (s, 6H), 1.68-1.87 (m, 6H), 1.37- 1.47 (m, 1H
0.173
0.153


 


680




415.7 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.59-7.63 (m, 2H), 7.32 (t, J = 8.8 Hz, 2H), 4.25 (d, J =  4.8 Hz, 2H), 4.13 (s, 2H), 3.97-4.04 (m, 1H), 3.88 (d, J = 4.8 Hz, 2H), 3.49- 3.54 (m, 1H), 3.41-3.47 (m, 2H), 3.25- 3.30 (m, 1H), 2.92 (s, 6H), 2.45-2.53 (m, 1H), 2.23- 2.28 (m, 1H), 2.01 (s, 6H)
0.085
0.173


 


681




454.1 (M + 1)
0.272
0.196


 


682




470.1 (M + 1)
0.124
0.111


 


683




454.1 (M + 1)
0.125
0.112


 


684




470.1 (M + 1)
0.03
0.017


 


685




474.1 (M + 1)
0.173
0.131


 


686




452.2 (M + 1)
0.628
0.524


 


687




412.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.70-7.74 (m, 2H), 7.21 (t, J = 8.4 Hz, 2H), 6.96 (d, J = 7.6 Hz, 2H), 6.62 (s, 1H), 6.50 (d, J = 7.6 Hz, 1H), 5.19 (s, 2H), 4.25 (s, 2H), 4.07 (s, 2H), 1.77 (s, 6H)
3.42 (NF54)
3.35


 


688




413.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.67-7.71 (m, 2H), 7.15- 7.21 (m, 2H), 6.92-6.97 (m, 2H), 6.71- 6.76 (m, 2H), 4.57-4.63 (dm, 1H), 3.76-3.79 (m, 1H), 3.68- 3.70 (m, 1H), 1.91 (s, 3H), 1.84 (s, 3H)
0.106 (NF54)
0.134


 


689




440.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.33-7.42 (m, 3H), 7.06- 7.08 (m, 1H), 6.70 (t, J = 9.2 Hz, 2H), 6.69-6.71 (m, 1H), 6.58- 6.62 (m, 1H), 4.38 (s, 2H), 3.66 (t, J = 8.0 Hz, 2H), 2.89 (t, J = 8.0 Hz, 2H), 2.25 (d, J = 1.6 Hz, 3H), 1.88-1.95 (m, 2H), 1.77 (s, 6H)
0.512
0.295


 


690




441.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.51-7.54 (m, 1H), 7.44- 7.48 (m, 1H), 7.37-7.42 (m, 1H), 7.05- 7.12 (m, 1H), 6.86 (dt, J = 1.6, 9.2 Hz, 1H), 6.57- 6.61 (m, 1H), 6.47-6.53 (m, 1H), 4.58 (d, J = 2.0 Hz, 2H), 3.91 (t, J = 6.0 Hz, 1H), 3.64-3.72 (m, 3H), 3.36 (s, 3H), 2.17 (d, J = 1.2 Hz, 2H), 1.91 (s, 3H), 1.89 (s, 3H)
0.866
0.76


 


691




455.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.37-7.43 (m, 2H), 7.31- 7.34 (m, 1H), 7.06-7.11 (m, 1H), 6.97 (t, J = 8.8 Hz, 1H), 6.71-6.73 (m, 1H), 6.58- 6.62 (m, 1H), 4.39 (s, 2H), 3.62-3.65 (m, 2H), 3.36 (br, 5H), 3.34 (s, 1H), 3.26 (s, 3H), 2.24 (d, J = 2.0 Hz, 3H), 1.79 (s, 6H)
0.068
0.06


 


692




469.2 (M + 1)
6.45
5.34


 


693




411.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.58-7.62 (m, 2H), 7.30 (d, J = 8.8 Hz, 2H), 7.21 (dd, J = 5.6, 8.8 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 4.23 (s, 2H), 4.06- 4.09 (m, 4H), 3.83 (d, J =  5.6 Hz, 2H), 2.05 (s, 6H)
0.008
0.008


 


694




407.3 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.59-7.62 (m, 2H), 7.29 (t, J = 8.4 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 4.19 (s, 2H), 4.04-4.08 (m, 4H), 3.80 (t, J = 4.8 Hz, 2H), 2.31 (s, 3H), 2.04 (s, 6H)
0.011
0.007


 


695




423.1 (M + 1)
0.017
0.019


 


696




429.2 (M + 1)
0.02
0.022


 


697




411.1 (M + 1)
0.362
0.256


 


698




415.3 (M + 1)
8.81
9.02


 


699




399.3 (M + 1)
0.678 (NF54)
ND


 


700




407.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.73-7.77 (m, 3H), 7.21- 7.30 (m, 6H), 4.82-4.86 (m, 1H), 4.13- 4.18 (m, 2H), 4.61 (s, 1H), 3.71-3.77 (m, 1H), 3.53- 3.58 (m, 1H), 3.09-3.21 (m, 1H), 2.34 (s, 3H), 2.01 (s, 3H), 1.99 (s, 3H)
>9.51
7.0


 


701




425.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.76-7.79 (m, 3H), 7.32- 7.38 (m, 1H), 7.28 (t, J = 8.8 Hz, 2H), 7.11 (d, J = 4.0 Hz, 1H), 7.06 (dt, J = 10, 2.4 Hz, 1H), 6.99 (dt, J = 2.8, 8.4 Hz, 1H), 4.62 (t, J = 6.4 Hz, 1H), 4.35 (t, J = 4.8 Hz, 2H), 3.84-3.98 (m, 2H), 2.79- 2.87 (m, 2H), 2.14-2.20 (m, 2H), 2.04 (s, 3H), 2.03 (s, 3H)
8.27
7.35


 


702




441.2 (M + 1)
6.03
5.85


 


703




399.3 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.81 (s, 1H), 7.76-7.80 (m, 2H), 7.29 (t, J = 8.8 Hz, 2H), 4.60-4.64 (m, 2H), 4.40- 4.43 (m, 2H), 3.92-3.95 (m, 2H), 2.05 (s, 3H), 2.04 (s, 3H), 1.70- 1.83 (m, 6H), 1.49-1.53 (m, 1H), 1.20- 1.42 (m, 4H),  0.99-1.35 (m, 2H)
8.57
8.29


 


704




393.3 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.42-7.46 (m, 2H), 7.31- 7.39 (m, 4H), 7.13 (t, J = 8.8 Hz, 2H), 4.09-4.12 (m, 4H), 3.82 (t, J = 4.8 Hz, 2H), 2.42 (s, 3H), 2.08 (s, 6H)
0.236
0.232


 


705




397.3 (M + 1)
1.241
0.76


 


706




431.2 (M + 1)
0.252
0.237


 


707




383.1 (M + 1)
6.54
>10


 


708




440.1 (M + 1)
0.809
1.134


 


709




413.1 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.67-7.71 (m, 2H), 7.09- 7.17 (m, 6H), 4.06 (s, 2H), 4.02 (t, J = 4.8 Hz, 2H), 3.80 (t, J = 4.8 Hz, 2H), 2.04 (s, 6H)
0.003
0.008


 


710




429.1 (M + 1)
0.028 (NF54)
ND


 


711




431.1 (M + 1)
0.034 (NF54)
ND


 


712




427.2 (M + 1)
0.019 (NF54)
ND


 


713




425.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.83-7.87 (m, 2H), 7.22 (t, J = 8.8 Hz, 2H), 7.16 (d, J =  8.4 Hz, 2H), 7.04 (d, J =  8.87 Hz, 2H), 4.11 (t, J =  4.4 Hz, 2H), 3.98 (s, 2H), 3.83 (t, J =  4.4 Hz, 2H), 2.29 (s, 3H), 1.98 (s, 6H)
0.008
ND


 


714




429.2 (M + 1)
0.007
0.004


 


715




429.1 (M + 1)
0.006
0.006


 


716




445.1 (M + 1)
0.002
0.001


 


717




439.2 (M + 1)
0.026
0.016


 


718




447.1 (M + 1)
0.008
0.006


 


719




445.1 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.58-7.62 (m, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.14 (t, J = 8.4 Hz, 2H), 6.89 (s, 1H), 6.67 (d, J = 7.6 Hz, 1H), 5.09 (s, 2H), 4.17 (s, 2H), 3.99 (s, 2H), 1.67 (s, 6H)
0.481
0.361


 


720




445.1 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.60-7.63 (m, 2H), 7.11 (t, J = 8.4 Hz, 2H), 6.75-6.80 (m, 1H), 6.59 (d, J = 4.8 Hz, 1H), 6.50 (br, 1H), 5.09 (s, 2H), 4.16 (s, 2H), 3.97 (s, 2H), 2.07 (s, 3H), 1.67 (s, 6H)
0.07
0.069


 


721




441.0 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.78-7.82 (m, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.35 (t, J = 8.8 Hz, 2H), 4.61-4.65 (m, 1H), 4.08 (s, 2H), 3.77- 3.92 (m, 3H), 2.43 (s, 3H), 2.07 (s, 3H), 2.05 (s, 3H)
0.042
ND


 


722




455.1 (M + 1)
0.381
0.281


 


723




463.1 (M + 1)
0.089
0.068


 


724




461.1 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.70-7.74 (m, 2H), 7.21 (t, J = 8.4 Hz, 2H), 6.96 (d, J = 7.6 Hz, 2H), 6.62 (s, 1H), 6.50 (d, J = 7.6 Hz, 1H), 5.19 (s, 2H), 4.25 (s, 2H), 4.07 (s, 2H), 1.77 (s, 6H)
0.509
0.287


 


725




457.1
5.21 (NF54)
ND


 


726




544.3 (M + 1)
1.925
1.48


 


727




634.3 (M + 1)
6.56
2.969


 


728




615.3 (M + 1)
5.4
1.485


 


729




705.3 (M + 1)
>10
6.29


 


730




601.2 (M + 1)
1.365
0.474


 


731




734.2 (M + 1)
2.27 (NF54)
5.61


 


732




905.4 (M + 1)
1.223 (NF54)
1.438


 


737




305.2 (M + 1) 1H NMR (400 MHz, CDCl3): δ 9.27 (s, 1H), 8.76 (d, J = 8.0 Hz, 1H), 8.55 (d, J = 3.2 Hz, 1H), 7.79 (t, J = 3.2 Hz, 1H), 7.33 (br, 1H), 6.99 (d, J = 8.4 Hz, 2H), 6.56 (d, J = 8.4 Hz, 2H), 3.87 (s, 2H), 3.14 (s, 2H), 2.22 (s, 3H), 2.02 (s, 4H)
7.85
4.09


 


738




328.5 (M + 1)
3.24
1.555


 


739




412.6 (M + 1)
0.768
0.881


 


740




367.2 (M + 1)
9.33
8.73


 


741




404.6 (M + 1)
5.25
4.83


 


742




388.2 (M + 1)
6.43
11.6


 


743




401.2 (M + 1)
2.675
3.003


 


744




437.6 (M + 1)
5.24
2.813


 


745




390.2 (M + 1)
3.57
4.23


 


746




382.2 (M + 1)
>10
6.94


 


747




388.2 (M + 1)
2.234
4.48


 


748




332.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 8.09 (s, 1H), 7.75-7.79 (m, 4H), 7.17 (t, J = 8.8 Hz, 2H), 6.93 (d, J = 8.0 Hz, 1H), 6.49 (d, J = 8.4 Hz, 2H), 2.35 (s, 3H), 2.14 (s, 3H)
3.44
4.15


 


749




360.8 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.64-7.67 (m, 2H), 7.20- 7.29 (m, 3H), 6.64 (dd, J = 2.8, 11.2 Hz, 1H), 6.55- 6.58 (m, 1H), 3.90 (t, J = 5.6 Hz, 2H), 3.11 (t, J = 5.6 Hz, 2H), 2.05-2.12 (m, 4H)
1.053
0.814


 


750




322.2 (M + 1)
4.77
4.96


 


751




318.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 8.39 (d, J = 6.8 Hz, 1H), 7.89-8.02 (m, 4H), 7.47 (dt, J = 1.2, 6.8 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H), 6.61 (d, J = 8.4 Hz, 2H), 2.24 (s, 3H)
1.792
4.55


 


752




370.8 (M + 1)
1.619
2.381


 


753




336.2 (M + 1) 1H NMR (400 MHz, CD3OD): δ 7.65-7.68 (m, 2H), 7.19 (t, J = 8.8 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 6.62 (dd, J = 2.0, 6.4 Hz, 1H), 4.00- 4.05 (m, 1H), 3.35-3.38 (m, 1H), 3.17- 3.24 (m, 1H), 3.05-3.14 (m, 1H), 2.24 (s, 3H), 2.12- 2.21 (m, 2H), 1.67-1.77 (m, 1H), 1.12 (d, J = 6.4 Hz, 3H)
0.376
0.592


 


754




374.8 (M + 1)
0.104
0.19









Assays
Compounds of the invention can be assayed to measure their capacity to inhibit proliferation of parasitemia in infected red blood cells. The proliferation is quantified by the addition of SYBR Green I (INVITROGEN)® dye which has a high affinity for double stranded DNA.
The following assay illustrates the invention without in any way limiting the scope of the invention. This parasite proliferation assay measures the increase in parasite DNA content using a DNA intercalating dye, SYBR Green®.
3D7 P. falciparum strain is grown in complete culturing media until parasitemia reaches 3% to 8% with O+ human erythrocytes. 20 μl of screening media is dispensed into 384 well assay plates. 50 nl of compounds of the invention (in DMSO), including antimalarial controls (mefloquine, pyrimethamine and artemisinin), are then transferred into the assay plates, as well as DMSO alone to serve as a negative control for inhibition. Then 30 μl of a suspension of a 3D7 P. falciparum infected erythrocytes in screening media is dispensed into the assay plates such that the final hematocrit is 2.5% with a final parasitemia of 0.3%. The plates are placed in a 37° C. incubator for 72 hours in a low oxygen environment containing 93% N2, 4% CO2, and 3% O2 gas mixture. 10 μl of lysis buffer (saponin, triton-X, EDTA) containing a 10× solution of SYBR Green I® in RPMI media is dispensed into the plates. The plates are lidded and kept at room temperature overnight for the lysis of the infected red blood cells. The fluorescence intensity is measured (excitation 425 nm, emission 530 nm) using the EnvisionTM system (Perkin Elmer). The percentage inhibition of 50%, EC50, is calculated for each compound.
Compounds of the invention have an EC50 of 10 μM or less, preferably less than 1 μM, 750 nM, 500 nM 400 nM, 300 nM, 200 nM, 100 nM and 50 nM. Compounds of the invention can significantly delay the increase in parasitemia.
Compounds of the invention can be assayed to measure their capacity to inhibit proliferation of kinetoplastid parasite Trypanosoma brucei. The proliferation is quantified by the addition of Cell Titer Glo (Promega®) a luminescent cell viability assay that measures the number of viable cells in culture based on the quantification of cellular ATP amount, which is an indicator of metabolically active cells.
The following assay illustrates the invention without in any way limiting the scope of the invention. This parasite proliferation assay measures the increase in parasite growth using an assay that measures ATP activity, Cell Titer Glo®.
Trypanosoma brucei Lister 427 strain is grown in HMI-9 Trypanosome media for T. brucei bloodstream form. 30 μl of HMI-9 media is dispensed into 384 well assay plates. 200 nl of compounds of the invention (in DMSO), including anti-trypanosome controls (Pentamidine and suramin), are then transferred into the assay plates, as well as DMSO alone to serve as a negative control for inhibition. Then 25 μl of a suspension of T. brucei culture in HMI-9 media is dispensed into the assay plates. The final concentration of parasites in culture corresponds to 1.7% of 0.5 uM ATP activity with Cell Titer Glo® in HMI-9 media. The plates are placed in a 37° C. incubator for 48 hours in an atmospheric environment containing 5% CO2. 40 μl of Cell Titer Glo® is dispensed into the plates. The plates are then read for luminescence. The percentage inhibition of 50%, EC50, is calculated for each compound.
Compounds of the invention have an EC50 of 10 μM or less, preferably less than 1 μM, 750 nM, 500 nM 400 nM, 300 nM, 200 nM, 100 nM and 50 nM. Compounds of the invention can significantly delay the proliferation of T. brucei. For example, 2-amino-1-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone (example 412) and 2-amino-1-(3-(3,4-difluorophenylamino)-2-(4-fluorophenyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-methylpropan-1-one (Example 29) have an EC50 of 10 μM and 7 μM, respectively.
It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference for all purposes.

## Claims

1. A method for prevention or treatment of malaria, comprising administering to a subject in need thereof a therapeutically effective amount of a compound and optionally in combination with one or more therapeutic agents, wherein the compound is of Formula 1a:




or a pharmaceutically acceptable salt thereof; in which:
Ra is selected from —X3NR7R8, —X3OR8, —X3S(O)0-2R8, —X3C(O)NR7R8, and benzyl optionally substituted with 1 to 3 radicals independently selected from halo, C1-4alkyl, halo-substituted-C1-4alkyl, C1-4alkoxy and halo-substituted-C1-4alkoxy; wherein X3 is selected from a bond and C1-4alkylene;
R1 is selected from —ORB, —C(O)OR13, —NR13R14, C6-10aryl and a saturated, unsaturated or partially unsaturated 4-9 member heterocyclic ring containing up to three nitrogens; wherein
R13 is selected from hydrogen, C1-6alkyl, halo-substituted-C1-6alkyl, hydroxy-substituted-C1-6alkyl, C6-10aryl-C0-4alkyl, C3-8cycloalkyl-C0-4alkyl, —X1NHC(O)R15, —X1C(NH)NHR15, —X1C(O)NHR15, —X1NHR15, —X1OR15, —C(O)R15 and —C(O)OR15; wherein X1 is selected from a bond and C1-4alkylene; R15 is selected from hydrogen, C1-6alkyl, halo-substituted-C1-6alkyl, and benzyl; and
R14 is selected from hydrogen, C1-6alkyl and hydroxy-substituted-C1-6alkyl;
any aryl or heterocyclic of R1 is optionally substituted with 1-3 radicals independently selected from halo, C1-6alkyl, halo-substituted-C1-6alkyl, C1-6alkoxy and halo-substituted-C1-6alkoxy;
or R13 and R14 together with the nitrogen to which R13 and R14 are attached form a saturated, unsaturated or partially unsaturated 5-9 member heterocyclic ring containing up to three heteroatoms selected from N, NR30, S(O)0-2 and O; wherein R30 is selected from hydrogen and C1-6alkyl; wherein said heterocyclic form the combination of R13 and R14 is optionally substituted with 1 to 3 radicals independently selected from halo, hydroxy, C1-6alkyl, amino-substituted-C1-6alkyl and halo-substituted-C1-6alkyl;

R2 is selected from hydrogen, C1-6alkyl, amino, C3-8cycloalkyl-C0-4alkyl, C6-10aryl-C0-4alkyl, halo-substituted-C1-6alkyl, hydroxy-substituted-C1-6alkyl and heterocyclyl-C0-4alkyl; wherein
said heterocyclyl is a saturated, unsaturated or partially unsaturated 5-9 member heterocyclic ring containing up to three heteroatoms selected from N, NR30, S(O)0-2 and O; wherein R30 is selected from hydrogen and C1-6alkyl;
said C6-10aryl or heterocyclic of R2 is optionally substituted with 1 to 3 radicals independently selected from halo, hydroxy, cyano, nitro, —NHR17, —(CH2)0-2NHC(O)R17, C1-6alkyl, halo-substituted-C1-6alkyl, amino-substituted-C1-6alkyl and C1-6alkoxy; wherein R17 is selected from hydrogen and C1-6alkyl;

R3 is selected from hydrogen, C1-6alkyl, C6-10aryl-C0-4alkyl, —X2C(O)OR16, —X2S(O)0-2R16, —X2OR16, —X2C(O)NHR16 and —X2NHC(O)R16; wherein
X2 is selected from a bond and C1-4alkylene; and
R16 is selected from hydrogen, C1-6alkyl and C6-10aryl-C0-4alkyl; wherein-said aryl of R16 is optionally substituted with 1 to 3 radicals independently selected from halo, C1-6alkyl, halo-substituted-C1-6alkyl, C1-6alkoxy and halo-substituted-C1-6alkoxy;

or R2 and R3 together with the carbon atom to which R2 and R3 are attached forms C3-8cycloalkyl;
or R2 and R13 together with the atoms to which R2 and R13 are attached form a ring selected from C3-8cycloalkyl and a saturated, unsaturated or partially unsaturated 5-9 member mono or fused heterocyclic ring containing up to three heteroatoms or groups selected from N, C(O), NR30, S(O)0-2 and O; wherein R30 is selected from hydrogen and C1-6alkyl; wherein said heterocyclic form the combination of R2 and R13 is optionally substituted with 1 to 3 radicals independently selected from halo, hydroxy, C1-6alkyl and halo-substituted-C1-6alkyl;
R4 is selected from hydrogen and C1-6alkyl;
R5 is selected from hydrogen and C1-6alkyl; or R4 and R5 together with the carbon atom to which R4 and R5 are attached forms C3-8cycloalkyl;
R6 is selected from C6-10aryl, C3-8cycloalkyl and a saturated, unsaturated or partially unsaturated 5-9 member mono or fused heterocyclic ring containing up to three heteroatoms or groups selected from N, C(O), NR30, S(O)0-2 and O; wherein R30 is selected from hydrogen and C1-6alkyl; wherein said aryl or heterocyclic of R6 is optionally substituted by 1 to 3 radicals independently selected from halo, hydroxy, C1-6alkyl and C1-6alkoxy;
R7 is selected from hydrogen, methyl, ethyl and isopropyl; and
R8 is selected from phenyl, benzyl, benzo[d][1,3]dioxol-5-yl, cyclobutyl, cyclopentyl, cycloheptyl, cyclohexyl, bicyclo[2.2.1]heptyl, tetrahydro-2H-pyranyl, pyridinyl, piperidinyl, piperazinyl, quinolinyl, pyrrolidinyl and pyrazolyl; wherein said phenyl, benzyl, benzo[d][1,3]dioxol-5-yl, cyclobutyl, cyclopentyl, cycloheptyl, cyclohexyl, bicyclo[2.2.1]heptyl, tetrahydro-2H-pyranyl, pyridinyl, piperidinyl, piperazinyl, quinolinyl, pyrrolidinyl or pyrazolyl of R8 is optionally substituted by 1 to 3 radicals independently selected from halo, cyano, methyl, ethyl, t-butyl, trifluoromethyl, trifluoromethoxy, dimethyl-amino, difluoromethoxy, carboxy, methoxy-carbonyl, methyl-sulfonyl-amino, methyl-sulfonyl, methyl-amino-carbonyl, phenyl, piperidinyl, piperidinyl-methyl, piperazinyl and piperazinyl-methyl;
R9 is selected from hydrogen and C1-6alkyl;
R10 is selected from hydrogen and C1-6alkyl;
R11 is selected from hydrogen and C1-6alkyl;
R12 is selected from hydrogen and C1-6alkyl;
or R11 and R12 combine to form C(O).

2. The method of claim 1, wherein the one or more therapeutic agents are selected from a kinase inhibitor, an anti-malarial drug and an anti-inflammatory agent.

3. The method of claim 2 wherein the anti-malarial drug is selected from proguanil, chlorproguanil, trimethoprim, chloroquine, mefloquine, lumefantrine, atovaquone, pyrimethamine-sulfadoxine, pyrimethamine-dapsone, halofantrine, quinine, quinidine, amodiaquine, amopyroquine, sulphonamides, artemisinin, arteflene, artemether, artesunate, primaquine, and pyronaridine.

4. The method of claim 3, wherein the compound of claim 1 is administered prior to, simultaneously with, or after the one or more therapeutic agents.

5. The method of claim 1, wherein said subject is a human.

6. The method of claim 1, wherein the compound in which R1 is selected from —OR13, —C(O)OR13, —NR13R14, phenyl, pyridinyl, indolyl, azetidinyl, 1H-indazolyl, piperidinyl and pyrimidinyl; wherein
R13 is selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, cyclopropyl, phenyl, benzyl, amino-butyl, hydroxy-ethyl, methoxy-ethyl, butoxy-ethyl, methoxy-propyl, —C(O)R15, —C(O)OR15, —X1OR15, —X1C(NH)NHR15, —X1NHC(O)R15 and X1C(O)NHR15; wherein X1 is selected from a bond and C1-4alkylene; and R15 is selected from hydrogen, methyl, ethyl, propyl, butyl, t-butyl, and trifluoromethyl and trifluoromethyl-carbonyl;
R14 is selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, isobutyl, hydroxy-ethyl, and isobutyl;
any phenyl, benzyl or heterocyclic of R1 is optionally substituted with 1-3 radicals independently selected from halo, methyl, ethyl, trifluoromethoxy and trifluoromethyl;
or R13 and R14 together with the nitrogen to which R13 and R14 are attached form pyrrolidinyl, morpholino, thiomorpholino and piperidinyl; wherein said heterocyclic form the combination of R13 and R14 is optionally substituted with 1 to 3 radicals independently selected from halo, trifluoromethyl, hydroxy and amino-ethyl;
R2 is selected from hydrogen, methyl, ethyl, isopropyl, propyl, isobutyl, butyl, t-butyl, trifluoromethyl, trifluoro-ethyl, phenyl, benzyl, phenethyl, cyclobutyl-methyl, cyclopentyl, cyclohexyl, cyclohexyl-methyl, hydroxy-methyl and 1-hydroxy-ethyl; wherein said phenyl, benzyl or phenethyl of R2 is optionally substituted with 1 to 3 radicals independently selected from halo, methoxy, trifluoromethyl, hydroxy, amino, nitro, cyano, amino-methyl, methyl-carbonyl-amino, —NHR17, —CH2NHC(O)R17 and —NHC(O)R17; wherein R17 is selected from hydrogen, ethyl, propyl, butyl and pentyl;
R3 is selected from hydrogen, methyl, methyl-carbonyl-amino-butyl, propyl-amino-carbonyl-methyl, carboxy-methyl, propyl-amino-carbonyl-methyl, butyl-amino-carbonyl-methyl, pentyl-amino-carbonyl-methyl, propyl-amino-carbonyl-ethyl, phenyl, benzyl-sulfanyl-methyl, benzoxy-carbonyl-methyl, methyl-sulfonyl-methyl, 1-(benzyloxy)ethyl, and benzoxy-carbonyl-ethyl;
or R2 and R3 together with the carbon atom to which R2 and R3 are attached form cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;
or R2 and R13 together with the atoms to which R2 and R13 are attached form piperidinyl, cyclobutyl, pyrrolidinyl, morpholino, piperidinyl, tetrahydrofuranyl, tetrahydro-2H-pyran-4-yl, indolyl, 2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl, oxopiperidin-3-yl, or 4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-6-yl.

7. The method of claim 6, wherein the compound in which R4, R5, R9 and R10 are independently selected from hydrogen and methyl; and R11 and R12 are both hydrogen; or R11 and R12 combine to form C(O).

8. The method of claim 7, wherein the compound in which R6 is selected from phenyl, cyclohexyl and pyridinyl; wherein said phenyl or pyridinyl of R6 is optionally substituted by 1 to 3 radicals independently selected from halo, pentyl, hydroxy, methyl and methoxy.

9. The method of claim 1, wherein the compound is of Formula Id:




or a pharmaceutically acceptable salt thereof; in which:
R1 is —NH2; R2 and R3 are independently selected from hydrogen and methyl;
R4 and R5 are independently selected from hydrogen and methyl;
R6 is phenyl substituted with a fluoro; and
R8 is a phenyl substituted with 1 to 2 radicals independently selected from chloro and fluoro.

10. The method of claim 1, wherein the compound is selected from:
2-amino-1-(3-(benzo[d][1,3]dioxol-5-ylamino)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone;
2-amino-1-{3-[(3,5-dimethylphenyl)amino]-2-phenyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[3-(2H-1,3-benzodioxol-5-ylamino)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-[3-(cyclopentylamino)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[3-(cyclopentylamino)-2-phenyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-2-methyl-1-[2-phenyl-3-(phenylamino)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
methyl 4-{[7-(2-amino-2-methylpropanoyl)-2-phenyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzoate;
2-amino-1-[2-(2-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-{3-[(4-fluorophenyl)amino]-2-phenyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(4-fluorophenyl)amino]-2-(2,4,6-trifluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-[2-(3,5-difluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-{3-[(4-fluorophenyl)amino]-2-(4-pentylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{2-cyclohexyl-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-(pyridin-3-ylamino)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-phenylpropan-1-one;
(2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-phenylpropan-1-one;
2-amino-1-{3-[(4-bromophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-(dimethylamino)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[3-(benzylamino)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
N-{2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}acetamide;
2-amino-1-[3-(cyclohexylamino)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2,3-bis(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(pyrrolidin-1-yl)ethan-1-one;
3-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(3-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(3-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(morpholin-4-yl)ethan-1-one;
4-{2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}thiomorpholine-1,1-dione;
2-(3,3-difluoropiperidin-1-yl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one;
7-[(1-aminocyclopropyl)carbonyl]-N,2-bis(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
N-{1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methyl-1-oxopropan-2-yl}acetamide;
2-amino-1-[2-(4-chlorophenyl)-3-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
benzyl N-{2-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}carbamate;
2-amino-3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
2-amino-1-[2-(4-fluoro-2-hydroxyphenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-fluorophenyl)amino]-2-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-fluorophenyl)amino]-2-(4-methoxyphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-bromophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-chlorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-(3,3-difluoropyrrolidin-1-yl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(3R)-3-fluoropyrrolidin-1-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(3S)-3-fluoropyrrolidin-1-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(4-fluoropiperidin-1-yl)ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[4-(trifluoromethyl)piperidin-1-yl]ethan-1-one;
2-(4,4-difluoropiperidin-1-yl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[3-(trifluoromethyl)piperidin-1-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(3-hydroxypiperidin-1-yl)ethan-1-one;
2-[(2,2-difluoroethyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(3,5-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(3,5-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-(cyclopropylamino)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(2-methylpropyl)amino]ethan-1-one;
2-amino-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-{[4-(trifluoromethyl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-{[4-(trifluoromethyl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-(3,3-difluoropiperidin-1-yl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)ethan-1-one;
1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(3,3-difluoropiperidin-1-yl)ethan-1-one;
1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(methylamino)ethan-1-one;
2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(2,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(2,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxypropan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-phenylethan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]butan-1-one;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(3R)-piperidin-3-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(3S)-piperidin-3-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2R)-pyrrolidin-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2S)-pyrrolidin-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2S)-piperidin-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2R)-piperidin-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(3R)-pyrrolidin-3-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(3S)-pyrrolidin-3-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
(2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylethan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylethan-1-one;
1-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}cyclopropan-1-ol;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-3-methylbutan-1-one;
N-[(5S)-5-amino-6-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-6-oxohexyl]acetamide;
N-[(5S)-5-amino-6-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-6-oxohexyl]-2,2,2-trifluoroacetamide;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxypropan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-phenylpropan-1-one;
2-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one;
(2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-phenylpropan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3,3-dimethylbutan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-phenylpropan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2,2-diphenylethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-(trifluoromethyl)butan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-methylpropan-1-one;
1-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}cyclopentan-1-ol;
1-{[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]carbonyl}cyclohexan-1-ol;
(2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-4-phenylbutan-1-one;
(2S)-2-cyclohexyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-(4-methoxyphenyl)ethan-1-one;
2-(3,5-difluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methoxy-2-phenylethan-1-one;
2-(4-bromophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-[4-(trifluoromethyl)phenyl]ethan-1-one;
3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methoxy-2-phenylpropan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-(3-hydroxyphenyl)ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-(4-hydroxyphenyl)ethan-1-one;
2-(2-chlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one;
2-(4-bromo-2-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one;
2-(4-chlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxyethan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-4-methylpentan-1-one;
(2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-phenylethan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-2-phenylethan-1-one;
7-[(1-aminocyclobutyl)carbonyl]-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
7-[(1-aminocyclopentyl)carbonyl]-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
7-[(1-aminocyclohexyl)carbonyl]-2-(4-fluorophenyl)-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-amino-4,4,4-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]butan-1-one;
2-amino-3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-3-cyclohexyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxypropan-1-one;
2-(benzylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-(dipropylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2S)-2-(dipropylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)-3-phenylpropan-1-one;
benzyl(4S)-4-{[(tert-butoxy)carbonyl]amino}-5-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-5-oxopentanoate;
benzyl (3 S)-3-{[(tert-butoxy)carbonyl]amino}-4-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxobutanoate;
2-(cyclopropylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
N-[4-({2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}amino)butyl]acetamide;
(2S)-2,6-diamino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]hexan-1-one;
(2S)-2-amino-3-(4-aminophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
N-[(5S)-5-amino-6-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-6-oxohexyl]butanamide;
N-{4-[(2S)-2-amino-3-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}acetamide;
2-[bis(2-hydroxyethyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxypropan-1-one;
2,2,2-trifluoro-N-[(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-1-oxopropan-2-yl]acetamide;
1-{2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl}guanidine;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(phenylamino)ethan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylbutan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3,3-dimethylbutan-1-one;
2-(4-chlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
2-(4-chlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylpropan-1-one;
2-(4-fluorophenyl)-7-{[(6S)-1H,4H,5H,6H,7H-imidazo[4,5-c]pyridin-6-yl]carbonyl}-N-(4-methylphenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
(2S)-2-(dimethylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-phenylpropan-1-one;
2-[4-(2-aminoethyl)piperidin-1-yl]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
tert-butyl N-[(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-(4-propanamidophenyl)propan-2-yl]carbamate;
tert-butyl N-[(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-(propylcarbamoyl)propan-2-yl]carbamate;
N-{4-[(2S)-2-amino-3-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}propanamide;
(4S)-4-amino-5-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-5-oxo-N-propylpentanamide;
(3S)-3-amino-4-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxo-N-propylbutanamide;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3,3,3-trifluoropropan-1-one;
(2R)-2-amino-3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
N-{4-[(2S)-2-amino-3-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}butanamide;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methoxypropan-1-one;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2R)-oxolan-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-{[(2S)-oxolan-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenoxybutan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenoxypropan-1-one;
2-(3-chlorophenoxy)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one;
(2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(pyrimidin-4-yl)ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methyl-2-(2-methylphenoxy)butan-1-one;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-[(oxan-4-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
(2S)-2-ethoxy-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(4-hydroxyphenyl)propan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(oxolan-2-yl)ethan-1-one;
2-(4-fluorophenyl)-N-(4-methylphenyl)-7-[(oxolan-3-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-(1-ethylpiperidin-4-yl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
N-({4-[(2S)-2-amino-3-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}methyl)butanamide;
N-({4-[(2S)-2-amino-3-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}methyl)propanamide;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(piperidin-4-yl)ethan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3,3,3-trifluoropropan-1-one;
(2R)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-phenylpropan-1-one;
(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-phenylpropan-1-one;
(2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylbutan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylbutan-1-one;
2-cyclopentyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(pyridin-4-yl)ethan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-(3,5-dichlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methyl-2-phenylbutan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(4-methylphenyl)ethan-1-one;
2-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-3-methylbutan-1-one;
benzyl(3S)-3-{[(tert-butoxy)carbonyl]amino}-4-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-oxobutanoate;
benzyl (3 S)-3-{[(tert-butoxy)carbonyl]amino}-4-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxobutanoate;
tert-butyl N-[(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-nitrophenyl)-1-oxopropan-2-yl]carbamate;
tert-butyl N-[(2S)-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(4-nitrophenyl)-1-oxopropan-2-yl]carbamate;
(3 S)-3-{[(tert-butoxy)carbonyl]amino}-4-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-oxobutanoic acid;
(3 S)-3-{[(tert-butoxy)carbonyl]amino}-4-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxobutanoic acid;
tert-butyl N-[(2S)-3-(4-aminophenyl)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-1-oxopropan-2-yl]carbamate;
tert-butyl N-[(2S)-3-(4-aminophenyl)-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxopropan-2-yl]carbamate;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-2,2-dimethylpropan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-2-(hydroxymethyl)-2-methylpropan-1-one;
tert-butyl N-[(2S)-3-(3-aminophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxopropan-2-yl]carbamate;
tert-butyl N-[(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-1-oxo-3-(propylcarbamoyl)propan-2-yl]carbamate;
tert-butyl N-[(2S)-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-(propylcarbamoyl)propan-2-yl]carbamate;
tert-butyl N-[(2S)-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-(pentylcarbamoyl)propan-2-yl]carbamate;
tert-butyl N-[(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-1-oxo-3-(4-pentanamidophenyl)propan-2-yl]carbamate;
tert-butyl N-[(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-1-oxo-3-(4-propanamidophenyl)propan-2-yl]carbamate;
tert-butyl N-[(2S)-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-(4-pentanamidophenyl)propan-2-yl]carbamate;
(3S)-3-amino-4-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-oxo-N-propylbutanamide;
(3S)-3-amino-4-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxo-N-propylbutanamide;
(3S)-3-amino-4-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxo-N-pentylbutanamide;
N-{4-[(2S)-2-amino-3-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-oxopropyl]phenyl}pentanamide;
N-{4-[(2S)-2-amino-3-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-oxopropyl]phenyl}propanamide;
N-{4-[(2S)-2-amino-3-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}pentanamide;
N-{4-[(2S)-2-amino-3-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-oxopropyl]phenyl}propanamide;
4-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile;
4-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile;
tert-butyl N-[(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-1-oxo-3-[4-(pentylamino)phenyl]propan-2-yl]carbamate;
2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl propanoate;
2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl butanoate;
2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl pentanoate;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-[4-(pentylamino)phenyl]propan-1-one;
(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-[(2-hydroxypropyl)amino]-3-phenylpropan-1-one;
(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-[(2-methoxyethyl)amino]-3-phenylpropan-1-one;
(2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxypropan-1-one;
(2R,3S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxybutan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-methanesulfonylbutan-1-one;
(3R)-3-amino-4-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-oxobutanoic acid;
(2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methanesulfonylpropan-1-one;
N-[(1S)-2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl]propanamide;
N-[(1S)-2-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-oxo-1-phenylethyl]butanamide;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)(methyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)(methyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
(2S)-2-(butylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-phenylethan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(pentylamino)-2-phenylethan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methoxypropan-1-one;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(pyridin-4-yl)ethan-1-one;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(1H-indol-1-yl)ethan-1-one;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(1-ethylpiperidin-4-yl)ethan-1-one;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(phenylamino)ethan-1-one;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(1H-indazol-3-yl)ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(propylamino)ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(pentylamino)ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(2-methoxyethyl)amino]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(3-methoxypropyl)amino]ethan-1-one;
(2R)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-phenylpropan-1-one;
(2S,3S)-2-amino-3-(benzyloxy)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}butan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylbutan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(1,3-thiazol-4-yl)propan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-fluorophenyl)propan-1-one;
(2S,3S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylpentan-1-one;
(2R)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylbutan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(3,4-difluorophenyl)propan-1-one;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methyl-2-(methylamino)propan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-methylpentan-1-one;
N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-[(morpholin-3-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-phenylpropan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-cyclobutylpropan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3,3-dimethylbutan-1-one;
(2R)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one;
4-[(2S)-2-amino-3-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-oxopropyl]benzonitrile;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-phenyl-2-(phenylamino)ethan-1-one;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-[2-(trifluoromethoxy)phenyl]ethan-1-one;
(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-phenylpropan-1-one;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-[4-fluoro-3-(trifluoromethyl)phenyl]ethan-1-one;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-phenoxyethan-1-one;
5-({3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}carbonyl)piperidin-2-one;
N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-{[(2S)-pyrrolidin-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
3-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4,4,4-trifluorobutan-1-one;
N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-{[(3S)-pyrrolidin-3-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-methylphenyl)propan-1-one;
N-(4-chloro-3-fluorophenyl)-7-[(2,3-dihydro-1H-isoindol-1-yl)carbonyl]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
N-(4-chloro-3-fluorophenyl)-7-{[(2S)-2,3-dihydro-1H-indol-2-yl]carbonyl}-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
(2R)-2-amino-3-(4-bromophenyl)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-{[(4-methoxyphenyl)methyl]sulfanyl}propan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4,4,4-trifluorobutan-1-one;
2-(2-butoxyethoxy)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-ethoxy-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(2-methoxyethoxyl)ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-6-methyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
5-{[7-(2-amino-2-methylpropanoyl)-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-fluorobenzonitrile;
2-{[2-chloro-4-(trifluoromethyl)phenyl]amino}-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylbutan-1-one;
N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-{[(2R)-oxolan-2-yl]carbonyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(1-methyl-1H-indol-3-yl)ethan-1-one;
(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-4-methylpentan-1-one;
(2R)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one;
2-[(3-chlorophenyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(4-methylphenyl)amino]ethan-1-one;
2-(4-chloro-3-fluorophenyl)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(4-methoxyphenyl)amino]-2-methylpropan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(3,4-dichlorophenyl)ethan-1-one;
2-amino-3,3,3-trifluoro-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-[(morpholin-2-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-[4-(trifluoromethyl)phenyl]ethan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(4-chlorophenyl)ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(4-methylphenyl)amino]-2-phenylethan-1-one;
N-(4-chloro-3-fluorophenyl)-2-(4-fluorophenyl)-7-[(4-methylmorpholin-2-yl)carbonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-amine;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(2-fluorophenyl)amino]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methyl-2-(phenylamino)propan-1-one;
2-amino-1-(3-{[4-fluoro-2-(trifluoromethyl)phenyl]amino}-2-(3-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)-2-methylpropan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methyl-2-(methylamino)butan-1-one;
(2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-methyl-2-(methylamino)pentan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-methyl-2-(methylamino)pentan-1-one;
2-amino-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-[(2,6-dimethylphenyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
2-amino-1-[2-(2-methoxyphenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-methylphenyl)amino]-2-(pyridin-4-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(3-chlorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-[(2,4-dimethylphenyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methyl-2-[(4-methylphenyl)amino]propan-1-one;
2-amino-1-[2-(2,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2S)-2-[benzyl(methyl)amino]-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)hexan-1-one;
1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(4-methylphenyl)ethan-1-one;
(2R)-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)pentan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}butan-1-one;
(2R)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-methylpentan-1-one;
2-amino-1-[2-(2,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
(2S)-2-amino-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylbutan-1-one;
2-amino-1-[2-(3-chlorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-2-methyl-1-{3-[(4-methylphenyl)amino]-2-(pyridin-4-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one;
2-(tert-butylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2S)-3-(4-chlorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-(methylamino)propan-1-one;
(2S)-2-amino-3-cyclopropyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2R)-2-(benzylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-(benzylamino)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-2-cyclopropyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2S)-2-amino-3-(3,4-difluorophenyl)-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-1-[2-(3,4-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-[(4-methylphenyl)amino]propan-1-one;
2-amino-1-[2-(2,5-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(3,4-dichlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2R)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methyl-2-(methylamino)butan-1-one;
2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(2,5-difluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
4-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile;
2-amino-1-{3-[(3,4-difluoro-5-methoxyphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(4-fluoro-3,5-dimethylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
(2S)-2-amino-3-cyclobutyl-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one;
(2R)-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one;
(2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(1,3-thiazol-4-yl)propan-1-one;
(2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-methylphenyl)propan-1-one;
(2S)-2-amino-3-(3,4-difluorophenyl)-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one;
(2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylbutan-1-one;
(2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one;
(2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(4-fluorophenyl)ethan-1-one;
(2S)-2-amino-2-cyclopropyl-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
(2S)-2-amino-3-cyclopropyl-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one;
(2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-methylpentan-1-one;
(2S)-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one;
(2S,3S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylpentan-1-one;
(2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-fluorophenyl)propan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}propan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylbutan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-cyclopropylethan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-cyclopropylpropan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-cyclobutylpropan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-4-methylpentan-1-one;
(2S,3S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-methylpentan-1-one;
(2S)-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one;
(2R)-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(4-fluorophenyl)ethan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-fluorophenyl)propan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(4-methylphenyl)propan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(3,4-difluorophenyl)propan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-(1,3-thiazol-4-yl)propan-1-one;
(2S)-2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3,3-dimethylbutan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylbutan-1-one;
(2S)-2-amino-2-cyclopropyl-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2S)-2-amino-3-cyclopropyl-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-3-cyclobutyl-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-methylpentan-1-one;
(2S,3S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylpentan-1-one;
(2S)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one;
(2R)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one;
(2S)-2-amino-2-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2S)-2-amino-3-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(4-methylphenyl)propan-1-one;
(2S)-2-amino-3-(3,4-difluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(1,3-thiazol-4-yl)propan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3,3-dimethylbutan-1-one;
(2S)-2-amino-3-cyclobutyl-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-4-methylpentan-1-one;
(2S,3S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-methylpentan-1-one;
(2S)-2-amino-2-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(4-methylphenyl)propan-1-one;
(2S)-2-amino-3-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-3-(3,4-difluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]propan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-(1,3-thiazol-4-yl)propan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-cyclopropylethan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3-cyclopropylpropan-1-one;
(2S)-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-hydroxy-3-methylbutan-1-one;
(2S)-2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-(4-fluorophenyl)ethan-1-one;
(2S)-2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-3,3-dimethylbutan-1-one;
2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(4-fluoro-3-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(3-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2S)-2-amino-3-(4-fluorophenyl)-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2,4-dimethylpentan-1-one;
(2S)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-2-methylpropan-1-one;
(2R)-2-amino-1-[2-(4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-3-hydroxy-2-methylpropan-1-one;
2-amino-1-[2-(4-fluoro-3-methylphenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluoro-3-methylphenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-[2-(3-chloro-4-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-chloro-3-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-chloro-3-fluorophenyl)-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
5-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-fluorobenzonitrile;
5-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-methylbenzonitrile;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-[3-(cyclohexylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(3-chloro-4-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(3-fluoro-4-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
4-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-chlorobenzonitrile;
N-(3-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}phenyl)methanesulfonamide;
3-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-N-methylbenzamide;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(3,4,5-trifluorophenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-methanesulfonylphenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-6,6-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
5-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-6,6-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-fluorobenzonitrile;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(3,4-dichlorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(4-fluoro-3-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
5-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-methylbenzonitrile;
4-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-chlorobenzonitrile;
(2S)-1-[2-(3-fluorophenyl)-5,5-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-methylbutan-1-one;
2-amino-1-[2-(3-fluorophenyl)-5,5-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-[2-(3-fluorophenyl)-5,5-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[(8S)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-(propan-2-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[(8R)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[(8S)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
(2S)-1-[2-(3-fluorophenyl)-5,5-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-hydroxy-3-phenylpropan-1-one;
2-amino-1-{3-[(1,5-dimethyl-1H-pyrazol-3-yl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(1-ethyl-1H-pyrazol-5-yl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[(8R)-3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-8-(propan-2-yl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-chlorophenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(3-fluorophenyl)-3-[(4-fluorophenyl)amino]-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(3,4-difluorophenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(3-chloro-4-fluorophenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-fluoro-3-methylphenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-chloro-3-methylphenyl)amino]-2-(3-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-fluoro-3-methylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
5-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-methylbenzonitrile;
2-amino-1-{3-[(3-fluoro-4-methylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-{3-[(3-chloro-4-methylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-(3-{[3-chloro-4-(trifluoromethyl)phenyl]amino}-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)-2-methylpropan-1-one;
2-amino-1-(3-{[4-fluoro-3-(trifluoromethyl)phenyl]amino}-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)-2-methylpropan-1-one;
4-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-(trifluoromethyl)benzonitrile;
5-{[7-(2-amino-2-methylpropanoyl)-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-fluorobenzonitrile;
2-amino-1-{3-[(3,4-dimethylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(3-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-{3-[(3-chlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-{[3-(trifluoromethoxy)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-{3-[(4-ethylphenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-(3-{[4-(difluoromethoxy)phenyl]amino}-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-{[4-(trifluoromethoxy)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
2-amino-1-{3-[(3,5-dichlorophenyl)amino]-2-(4-fluorophenyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}-2-methylpropan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-phenylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-ethylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[4-(trifluoromethoxy)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[3-(trifluoromethoxy)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(3-chlorophenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[3-(trifluoromethyl)phenyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
3-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}benzonitrile;
2-amino-1-{3-[(3,4-dimethylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
4-{[7-(2-aminoacetyl)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]amino}-2-(trifluoromethyl)benzonitrile;
2-amino-1-{3-[(3,5-dimethylphenyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-(3-{[4-fluoro-3-(trifluoromethyl)phenyl]amino}-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)ethan-1-one;
2-amino-1-(3-{[3-chloro-4-(trifluoromethyl)phenyl]amino}-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl)ethan-1-one;
2-amino-1-{3-[(4-chloro-3-methylphenyl)amino]-2-(4-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4,4-difluorocyclohexyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-phenylcyclohexyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-{[4-(trifluoromethyl)cyclohexyl]amino}-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-tert-butylcyclohexyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(2-methylcyclohexyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[3-(cycloheptylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(3,3,5-trimethylcyclohexyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(1R,2R,4S)-bicyclo[2.2.1]heptan-2-ylamino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[3-(cyclopentylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[3-(cyclobutylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-(oxan-4-ylamino)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-chloro-3-fluorophenyl)amino]-2-(4-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)amino]-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-5,5-dimethyl-3-[(4-methylphenyl)amino]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-chlorophenyl)amino]-2-(4-fluorophenyl)-5,5-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-chlorophenyl)(methyl)amino]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)methyl]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylphenyl)methyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-methoxyphenyl)methyl]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(3,4-difluorophenyl)methyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)methyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one;
7-(2-aminoacetyl)-N,2-bis(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazine-3-carboxamide;
2-amino-1-[3-(4-fluorophenoxy)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[3-(4-chlorophenoxy)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[3-(3,4-difluorophenoxy)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[3-(4-fluoro-3-methylphenoxy)-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylphenyl)sulfanyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(3-fluorophenyl)sulfanyl]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-3-[(4-fluorophenyl)sulfanyl]-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(4-chlorophenyl)sulfanyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(3,5-dimethylphenyl)sulfanyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(3,4-difluorophenyl)sulfanyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(3-fluorobenzene)sulfinyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-fluorobenzene)sulfinyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylbenzene)sulfinyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one;
2-amino-1-{3-[(3,5-dimethylbenzene)sulfinyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(3,4-difluorobenzene)sulfinyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one;
2-amino-1-{3-[(4-chlorobenzene)sulfinyl]-2-(4-fluorophenyl)-8,8-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one; and
2-amino-1-[2-(4-fluorophenyl)-8,8-dimethyl-3-[(4-methylbenzene)sulfonyl]-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl]ethan-1-one.

11. The method of claim 1, wherein the compound is 2-amino-1-(2-(4-fluorophenyl)-3-(4-fluorophenylamino)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone having the formula:

12. The method of claim 1, wherein the compound is 2-amino-1-(3-(3,4-difluorophenylamino)-2-(4-fluorophenyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-methylpropan-1-one of the formula:

13. The method of claim 1, wherein the compound is 2-amino-1-(3-(4-chlorophenylamino)-2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone having the formula: