Novel Compounds

A method of treating, including prophylaxis, in a mammal in need thereof a CSBP/RK/p38 kinase mediated disease selected from the group consisting of

• a) diabetic retinopathy, macular degeneration, age related macular degeneration, retinitis, retinopathies, uveitis, ocular photophobia, acute injury to the eye tissue, corneal graft rejection, ocular neovascularization, retinal neovascularization (including neovascularization following injury or infection), retrolental fibroplasias, neovascular glaucoma, optic neuropathy, optic neuritis, retinal ischemia, laser induced optic damage, and surgery or trauma induced proliferative vitroretinopathy;
• b) Depression, mood disorders, Major Depressive Episode, Manic Episode, Mixed Episode and Hypomanic Episode, Major Depressive Disorder, Dysthymic Disorder, Bipolar I Disorder, Bipolar II Disorder, Cyclothymic Disorder, Mood Disorder Due to a General Medical Condition, and Substance-Induced Mood Disorder;
• c) Schizophrenia, Paranoid Type;
• Schizophrenia Disorganised Type;
• Schizophrenia Catatonic Type;
• Schizophrenia, Undifferentiated Type;
• Schizophrenia, Residual Type;
• Schizophreniform Disorder;
• Schizoaffective Disorder;
• Delusional Disorder;
• Brief Psychotic Disorder;
• Shared Psychotic Disorder;
• Psychotic Disorder Due to a General Medical Condition;
• and Psychotic Disorder Not Otherwise Specified;
• d) Anxiety;
• Panic Attack;
• Panic Disorder;
• Panic Disorder without Agoraphobia;
• Panic Disorder with Agoraphobia;
• Agoraphobia;
• Agoraphobia Without History of Panic Disorder;
• Simple Phobia;
• Specific Phobia-Animal Type;
• Specific Phobia-Natural Specific;
• Phobia-Environment Type;
• Specific Phobia-Blood-Injection-Injury Type;
• Specific Phobia-Situational Type;
• Social Phobia;
• Obsessive-Compulsive Disorder;
• Posttraumatic Stress Disorder;
• Acute Stress Disorder;
• Generalized Anxiety Disorder;
• Anxiety Disorder Due to a General Medical Condition;
• Substance-Induced Anxiety Disorder;
• Separation Anxiety Disorder;
• Adjustment Disorders with Anxiety;
• and Anxiety Disorder Not Otherwise Specified;
• e) Sleep disorders;
• Dyssomnias;
• Primary Insomnia;
• Primary Hypersomnia;
• Narcolepsy;
• Breathing-Related Sleep Disorders;
• Circadian Rhythm Sleep Disorder;
• Dyssomnia Not Otherwise Specified;
• Parasomnias;
• Nightmare Disorder;
• Sleep Terror Disorder;
• Sleepwalking Disorder;
• and Parasomnia Not Otherwise Specified;
• Sleep Disorders Related to Another Mental Disorder;
• Insomnia Related to Another Mental Disorder;
• Hypersomnia Related to Another Mental Disorder;
• Sleep Disorder Due to a General Medical Condition;
• Sleep Disturbances associated with a diseases selected from neurological disorders, neuropathic pain, restless leg syndrome, heart and lung diseases;
• Substance-Induced Sleep Disorder;
• Substance-Induced Sleep Disorder, Insomnia Type;
• Substance-Induced Sleep Disorder, Hypersomnia Type;
• Substance-Induced Sleep Disorder, Parasomnia Type;
• Substance-Induced Sleep Disorder, Mixed Type;
• Sleep Apnea;
• and Jet-lag Syndrome;
• comprising administering to said mammal an effective amount of a compound according to the formula:
• wherein
• G1, and G2 are independently nitrogen;
• G3 is CH2;
• G4 is CH;
• R1 is C(Z)N(R10′)(CR10R20)vRb, C(Z)O(CR10R20)vRb, N(R10′)C(Z)(CR10R20)vRb, N(R10′)C(Z)N(R10′)(CR10R20)vRb, or N(R10′)OC(Z)(CR10R20)vRb;
• R1′ is independently selected at each occurrence from halogen, C1-4 alkyl, halo-substituted-C1-4 alkyl, cyano, nitro, (CR10R20)v′NRdRd′, (CR10R20)v′C(O)R12, SR5, S(O)R5, S(O)2R5, or (CR10R20)v′OR13;
• Rb is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl C1-10 alkyl, aryl, arylC1-10alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic, or heterocyclylC1-10 alkyl moiety, which moieties, excluding hydrogen, may all be optionally substituted;
• X is R2, OR2′, S(O)mR2′, (CH2)n′N(R10′)S(O)mR2′, (CH2)n′N(R10′)C(O)R2′, (CH2)n′NR4R14, (CH2)n′N(R2′)(R2″), or N(R10′)RhNH—C(═N—CN)NRqRq′;
• X1 is N(R11), O, S(O)m, or CR10R20;
• Rh is selected from an optionally substituted C1-10 alkyl, —CH2—C(O)—CH2—, —CH2—CH2—O—CH2—CH2—, —CH2—C(O)N(R10′)CH2—CH2—, —CH2—N(R10′)C(O)CH2—, —CH2—CH(OR10′)—CH2—, —CH2—C(O)O—CH2—CH2—, or —CH2—CH2—O—C(O)CH2—;
• Rq and Rq′ are independently selected at each occurrence from hydrogen, C1-10 alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-10alkyl, C5-7 cycloalkenyl, C5-7 cycloalkenyl-C1-10alkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic, or a heterocyclylC1-10 alkyl moiety, wherein all of the moieties except for hydrogen, are optionally substituted, or Rq and Rq′ together with the nitrogen to which they are attached form an optionally substituted heterocyclic ring of 5 to 7 members, which ring may contain an additional heteroatom selected from oxygen, nitrogen or sulfur;
• R2 is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic, or a heterocyclylC1-10 alkyl moiety, and wherein each of these moieties, excluding hydrogen, may be optionally substituted;
• or
• R2 is the moiety (CR10R20)q′X1(CR10R20)qC(A1)(A2)(A3), or (CR10R20)q′C(A1)(A2)(A3);
• R2′ is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic, or a heterocyclylC1-10 alkyl moiety, and wherein each of these moieties, excluding hydrogen, may be optionally substituted;
• R2″ is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic, or a heterocyclylC1-10 alkyl moiety, and
• wherein these moieties, excluding hydrogen, may be optionally;
• or
• wherein R2″ is the moiety (CR10R20)tX1(CR10R20)qC(A1)(A2)(A3);
• A1 is an optionally substituted C1-10 alkyl, heterocyclic, heterocyclic C1-10 alkyl, heteroaryl, heteroaryl C1-10 alkyl, aryl, or aryl C1-10 alkyl;
• A2 is an optionally substituted C1-10 alkyl, heterocyclic, heterocyclic C1-10 alkyl, heteroaryl, heteroaryl C1-10 alkyl, aryl, or aryl C1-10 alkyl;
• A3 is hydrogen or is an optionally substituted C1-10 alkyl;
• R3 is a C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl C1-10 alkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic or a heterocyclylC1-10 alkyl moiety, and wherein each of these moieties may be optionally substituted;
• R4 and R14 are each independently selected at each occurrence from hydrogen, C1-4 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylC1-4alkyl, aryl, aryl-C1-4 alkyl, heterocyclic, heterocyclic C1-4 alkyl, heteroaryl or a heteroaryl C1-4 alkyl moiety, and wherein each of these moieties, excluding hydrogen, may be optionally substituted;
• or the R4 and R14 together with the nitrogen which they are attached form an optionally substituted heterocyclic ring of 4 to 7 members, which ring optionally contains an additional heteroatom selected from oxygen, sulfur or nitrogen;
• R4′ and R14′ are each independently selected at each occurrence from hydrogen or C1-4 alkyl, or R4′ and R14′ together with the nitrogen to which they are attached form a heterocyclic ring of 5 to 7 members, which ring optionally contains an additional heteroatom selected from NR9′;
• R5 is independently selected at each occurrence from hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl or NR4′R14′, excluding the moieties SR5 being SNR4R14′, S(O)2R5 being SO2H and S(O)R5 being SOH;
• R9′ is independently selected at each occurrence from hydrogen, or C1-4 alkyl;
• R10 and R20 are independently selected at each occurrence from hydrogen or C1-4alkyl;
• R10′ is independently selected at each occurrence from hydrogen or C1-4alkyl;
• R11 is independently selected at each occurrence from hydrogen or C1-4alkyl;
• R12 is independently selected at each occurrence from hydrogen, C1-4 alkyl, halo-substituted C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-7 cycloalkyl, C3-7cycloalkylC1-4 alkyl, C5-7 cycloalkenyl, C5-7cycloalkenyl C1-4 alkyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4 alkyl, heterocyclyl, or a heterocyclylC1-4 alkyl moiety, and wherein each of these moieties, excluding hydrogen, may be optionally substituted;
• R13 is independently selected at each occurrence from hydrogen, C1-4 alkyl, halo-substituted C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-7 cycloalkyl, C3-7cycloalkylC1-4 alkyl, C5-7 cycloalkenyl, C5-7cycloalkenyl C1-4 alkyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4 alkyl, heterocyclyl, or a heterocyclylC1-4 alkyl moiety, and wherein each of these moieties, excluding hydrogen, may be optionally substituted;
• Rd and Rd′ are each independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkylC1-4alkyl moiety, and wherein each of these moieties, excluding hydrogen, may be optionally substituted;
• or Rd and Rd′ together with the nitrogen which they are attached form an optionally substituted heterocyclic ring of 5 to 6 members, which ring optionally contains an additional heteroatom selected from oxygen, sulfur or NR9′;
• g is 0 or an integer having a value of 1, 2, 3, or 4;
• n′ is independently selected at each occurrence from 0 or an integer having a value of 1 to 10;
• m is independently selected at each occurrence from 0 or an integer having a value of 1 or 2;
• q is 0 or an integer having a value of 1 to 10;
• q′ is 0, or an integer having a value of 1 to 6;
• t is an integer having a value of 2 to 6;
• v is 0 or an integer having a value of 1 or 2;
• v′ is independently selected at each occurrence from 0 or an integer having a value of 1 or 2;
• Z is independently selected at each occurrence from oxygen or sulfur;
• and
• a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof.