Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity

A method of treating a condition selected from the group consisting of headache, neuropathic pain, chronic inflammatory pain, visceral pain, neuroinflammation, medication-induced hyperalgesia and/or allodynia, acute pain, chronic pain, and bone cancer pain in a mammal, wherein said method comprises administering an effective amount of a compound

• wherein,
• Q is S—(CHR6)1;
• R1 and each R6 is, independently, H, optionally substituted C1-6 alkyl, optionally substituted C1-4 alkaryl, optionally substituted C1-4 alkheterocyclyl, optionally substituted C2-9 heterocyclyl, optionally substituted C3-8 cycloalkyl, optionally substituted C1-4 alkcycloalkyl, or —(CR1AR1B)nNR1CR1D;
• R1A and R1B are, independently, H, hydroxy, halo, optionally substituted C1-6 alkyl, optionally substituted C1-6 alkoxy, optionally substituted C1-4 alkcycloalkyl, optionally substituted C1-4 alkaryl, optionally substituted C1-4 alkheterocyclyl, optionally substituted C1-4 alkheteroaryl, optionally substituted C3-8 cycloalkyl, or optionally substituted C2-9 heterocyclyl, or R1A and R1B combine to form ═O;
• R1C and R1D are, independently, H, optionally substituted C1-6 alkyl, optionally substituted C1-6 alkoxy, optionally substituted C1-4 alkcycloalkyl, optionally substituted C1-4 alkaryl, optionally substituted C1-4 alkheterocyclyl, optionally substituted C1-4 alkheteroaryl, optionally substituted C3-8 cycloalkyl, optionally substituted C2-9 heterocyclyl, or an N-protecting group selected from the group consisting of formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, o-nitrophenoxyacetyl, α-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, alaninyl, leucinyl, phenylalaninyl, benzenesulfonyl, p-toluenesulfonyl, benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, 1-(p-biphenylyl)-1-methylethoxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxy carbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2,-trichloroethoxycarbonyl, phenoxycarbonyl, 4-nitrophenoxy carbonyl, fluorenyl-9-methoxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl, benzyl, triphenylmethyl, benzyloxymethyl, and trimethylsilyl, or R1C and R1D combine to form an optionally substituted C2-9 heterocyclyl;
• n is an integer between 1-6;
• each of R2 and R3 is, independently, H, hal, optionally substituted C1-6 alkyl, optionally substituted C6-10 aryl, optionally substituted C1-6 alkaryl, optionally substituted C2-9 heterocyclyl, hydroxy, optionally substituted C1-6 alkoxy, optionally substituted C1-6 thioalkoxy, (CH2)r2NHC(NH)R2A, or (CH2)r2NHC(S)NHR2B, or optionally substituted C1-4 alkheterocyclyl,
• wherein r2 is an integer from 0 to 2, R2A is optionally substituted C1-6 alkyl, optionally substituted C6-10 aryl, optionally substituted C1-4 alkaryl, optionally substituted C2-9 heterocyclyl, optionally substituted C1-4 alkheterocyclyl, optionally substituted C1-6 thioalkoxy, optionally substituted C1-4 thioalkaryl, optionally substituted aryloyl, optionally substituted C1-4 thioalkheterocyclyl, or;
• and
• R2B is optionally substituted C1-4 alkaryl, optionally substituted C2-9 heterocyclyl, substituted C1-4 alkheterocyclyl, optionally substituted C1-6 thioalkoxy, optionally substituted C1-4 thioalkaryl, optionally substituted aryloyl, optionally substituted C1-4 thioalkheterocyclyl, or optionally substituted amino;
• and
• each of R4 and R5 is independently H, hal, (CH2)r2NHC(NH)R2A, or (CH2)r2NHC(S)NHR2B;
• wherein Y1 and Y2 are each H, or Y1 and Y2 together are ═O, or Y1 and Y2 are independently H, optionally substituted C1-6 alkyl, optionally substituted C6-10 aryl, optionally substituted C1-6 alkaryl, optionally substituted C2-9 heterocyclyl, hydroxy, optionally substituted C1-6 alkoxy, optionally substituted C1-6 thioalkoxy, or optionally substituted C1-4 alkheterocyclyl;
• wherein one and only one of R2, R3, R4, and R5 is (CH2)r2NHC(NH)R2A or (CH2)r2NHC(S)NHR2B;
• or a pharmaceutically acceptable salt thereof to said mammal.