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Microwave promoted novel and efficient one-step parallel synthesis of dibenzopyranones and heterocyclic analogues from bromo arylcarboxylates and o-hydroxyarylboronic acids via Suzuki-Miyaura cross coupling reaction is described. Spontaneous lactonization gave dibenzopyranones and heterocyclic analogues bearing electron donating and withdrawing groups on both aromatic rings in good to excellent yields.

Stearoyl-CoA desaturase-1 (SCD1) catalyzes de novo synthesis of monounsaturated fatty acids from saturated fatty acids. Studies have demonstrated that rodents lacking a functional SCD1 gene have an improved metabolic profile, including reduced weight gain, lower triglycerides, and improved insulin response. In this study, we discovered a series of piperazinylpyridazine-based highly potent, selective, and orally bioavailable compounds. Particularly, compound 49 (XEN103) was highly active in vitro (mSCD1 IC(50) = 14 nM and HepG2 IC(50) = 12 nM) and efficacious in vivo (ED(50) = 0.8 mg/kg). It also demonstrated striking reduction of weight gain in a rodent model. Our findings with small-molecule SCD1 inhibitors confirm the importance of this target in metabolic regulation, describe novel models for assessing SCD1 inhibitors for efficacy and tolerability and demonstrate an opportunity to develop a novel therapy for metabolic disease.

Addition of a small amount of coumarin during crystallization produces new polymorphic modifications in 4-styrylcoumarin and 4-(3-fluorostyryl)coumarin, which are photolabile. Interestingly, upon irradiation polymorphic modification of 4-(3-fluorostyryl)coumarin produces a mirror-symmetric photodimer in contrast to the centrosymmetric photodimer obtained without addition of coumarin during crystallization.

(1E,3E)-1,4-Diphenylbuta-1,3-diene is photostable in the crystalline state, while fluoro-substitution induces reactivity. Crystals of (1E,3E)-1-pentafluorophenyl-4-(4-methoxyphenyl)buta-1,3-diene 1, (1E,3E)-1-pentafluorophenyl-4-(4-methylphenyl)buta-1,3-diene 2 and (1E,3E)-l-pentafluorophenyl-4-phenylbuta-1,3-diene 3 undergo double [2+2] photodimerization topochemically to yield anti head-to-tail photodimers in the crystalline state. Remarkably fluoro-substitution brings the reactant molecules into an anti head-to-tail arrangement in the crystal lattice with weak intermolecular interactions: C-H ... F, F ... F, C-H ... pi, pi ... pi.

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Styryl coumarins generally yield centrosymmetric (a-mode, anti-HT) photodimers when subjected to irradiation in the solid state. However, the substitution of fluorine dramatically alters the packing mode and steers the molecules 4-(4-fluorostyryl)coumarin 1 and 4-(2-fluorostyryl)coumarin 2 to form a stereospecific photodimer, p-mode, syn-HH across the styrenic double bond (yield 78-85%). The stereochemistry of the photodimer 2a has been established by X-ray crystallography. There is no evidence for the presence of C-H --F interactions. The true nature of the weak atom-atom interactions called into play when fluorine is substituted is not clear. It is observed that the fluoro substituted compounds have greater crystal density than the corresponding unsubstituted ones.