Compounds as mPGES-1 inhibitors

A method for treating a disease or condition mediated by enhanced mPGES-1 expression or activity, wherein the method comprises the step of administering to a subject suffering from the disease or condition an effective amount of a compound represented by general structure (I):

• wherein,
• T is represented by structure (IIIa) or (IIIb):
• wherein each R7 is individually a C1-C6 alkyl moiety;
• L is a linker selected from:
• —(CH2)2—,
• —(CH2)2NHC(O)CH2—,
• —(CH2)3—,
• —(CH2)2NHC(NH2)═,
• —(CH2)2NHC(O)CH2NHC(NH2)═,
• —(CH2)3NHC(NH2)═,
• —(CH2)2NHC(Me)═,
• —(CH2)2NHC(O)CH2NHC(Me)═,
• —(CH2)3NHC(Me)═,
• —(CH2)2NR1′C(NH2)═,
• —C(CO2H)(CH2)3—,
• —C(CO2H)(CH2)3NHC(NH2)═,
• —C(CO2H)CH2—,
• —C(CO2H)(CH2)2—,
• —C(CO2H)(CH2)4—,
• —(CH2)4—,
• —(CH2)5—,
• —CHR2′C(O)—,
• —CHR2′CH2—,
• —CHR5CH2NR5′C(Me)═,
• —CHR2′(CH2)2—,
• —(CH2)2CHR1′—,
• —(CH2)2CHR1′NHC(O)C(Me)—,
• —CH2CHR1′—,
• —CH2CHR1′NHC(Me)═,
• —CHR5(CH2)2CHR5′—,
• —CHR2′CHR3′ (CH2)2—, and
• —CR5═CH—CH═CR5′—CH2—,
• wherein R5 and R5′ represent the connection of a second linker between one backbone atom of the linker, bearing R5, and another backbone atom of the linker, bearing R5′, wherein R5′ is joined with R5 via the second linker, thus forming a 4-10-membered cyclic structure;
• N* is represented by structure (IIa) or (IIb)
• R1 and R2 are each independently selected from hydrogen (H), C1-C6 alkyl or C1-C6 alkenyl, or R1 and R2 are joined together and thus form a second linker between the amide nitrogen atom and the distal nitrogen atom, or R1 is joined with R1′ of the linker L in a cyclic structure and/or R2 is joined with R2′ of the linker L in a cyclic structure;
• R3 is selected from hydrogen (H), C1-C6 alkyl or C1-C6 alkenyl, wherein the alkyl or alkenyl moiety may be substituted with one or more halogen atoms, hydroxyl moieties or (halo)alkoxy moieties, or R3 is absent when the distal nitrogen atom is part of an imine moiety;
• or optionally R3 is joined with R3′ of the linker L in a cyclic structure;
• and
• R4 is selected from hydrogen (H) or C1-C6 alkyl, wherein the alkyl moiety may be substituted with one or more halogen atoms or (halo)alkoxy moieties;
• X is an anion,
• wherein the disease or condition is selected from the group consisting of:
• acute and chronic inflammation, dermatitis, eczema, psoriasis, burns, acne vulgaris, hidradenitis suppurativa, tissue trauma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, diverticulitis, irritable bowel disease (IBS), peptic ulcers, cystitis, prostatitis, pancreatitis, nephritis, influenza, rhinitis, pharyngitis, tonsillitis, conjunctivitis, iritis, scleritis, otitis, uveitis, inflammation related anorexia, an allergy, pelvic inflammatory disease, reperfusion injury, transplant rejection, tendinitis, vasculitis, phlebitis, acute pain, chronic pain, neuropathic pain, nociceptive pain, hyperalgesia, pain related to central sensitization, allodynia inflammatory pain, visceral pain, cancer pain, trauma pain, dental or surgery pain, postoperative pain, delivery pain, childbirth ache, persistent pain, peripheral mediated pain, central mediated pain, chronic headache, migraine, sinus headaches, tension headaches, phantom limb pain, peripheral nerve injury chemotherapy pain, cancer pain, arthritis, juvenile arthritis, ankylosing spondylitis, gout, rheumatic fever, bursitis, systemic lupus erythematosus (SLE), multiple sclerosis, sarcoidosis, pulmonary fibrosis, brain cancer, prostate cancer, kidney cancer, liver cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, head and neck cancer, thyroid cancer, glioblastoma, melanoma, lymphoma, leukemia, skin T-cell lymphoma, skin B-cell lymphoma, diabetic vasculopathy, diabetic neuropathy, diabetic retinopathy, thrombosis, and coronary heart disease.