DSP-0509, a systemically available TLR7 agonist, exhibits combination effect with immune checkpoint blockade by activating anti-tumor immune effects.

TLR7 is an innate immune receptor that recognizes single-stranded RNAs, and its activation leads to anti-tumor immune effects. Although it is the only approved TLR7 agonist in cancer therapy, imiquimod is allowed to be administered with topical formulation. Thus, systemic administrative TLR7 agonist is expected in terms of expanding applicable cancer types. Here, we demonstrated the identification and characterization of DSP-0509 as a novel small-molecule TLR7 agonist. DSP-0509 is designed to have unique physicochemical features that could be administered systemically with a short half-life. DSP-0509 activated bone marrow-derived dendritic cells (BMDCs) and induced inflammatory cytokines including type I interferons. In the LM8 tumor-bearing mouse model, DSP-0509 reduced tumor growth not only in subcutaneous primary lesions but also in lung metastatic lesions. DSP-0509 inhibited tumor growth in several syngeneic tumor-bearing mouse models. We found that the CD8+ T cell infiltration of tumor before treatment tended to be positively correlated with anti-tumor efficacy in several mouse tumor models. The combination of DSP-0509 with anti-PD-1 antibody significantly enhanced the tumor growth inhibition compared to each monotherapy in CT26 model mice. In addition, the effector memory T cells were expanded in both the peripheral blood and tumor, and rejection of tumor re-challenge occurred in the combination group. Moreover, synergistic anti-tumor efficacy and effector memory T cell upregulation were also observed for the combination with anti-CTLA-4 antibody. The analysis of the tumor-immune microenvironment by using the nCounter assay revealed that the combination of DSP-0509 with anti-PD-1 antibody enhanced infiltration by multiple immune cells including cytotoxic T cells. In addition, the T cell function pathway and antigen presentation pathway were activated in the combination group. We confirmed that DSP-0509 enhanced the anti-tumor immune effects of anti-PD-1 antibody by inducing type I interferons via activation of dendritic cells and even CTLs. In conclusion, we expect that DSP-0509, a new TLR7 agonist that synergistically induces anti-tumor effector memory T cells with immune checkpoint blockers (ICBs) and can be administered systemically, will be used in the treatment of multiple cancers.

Comprehensive analysis of protein-expression changes specific to immunoglobulin G4-related disease.

BACKGROUND AND AIMS: Immunoglobulin 4 (IgG4)-related disease (IgG4-RD) is a lymphoproliferative disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4-positive plasma cells. We analyzed the serum proteins, whose levels varied based on the disease state and treatment. MATERIALS AND METHODS: Serum proteins from patients with IgG4-related disease and healthy subjects were resolved using two-dimensional electrophoresis, silver-stained, and scanned. Alternatively, the proteins were labeled with Cy2, Cy3, and Cy5 before electrophoresis. The proteins, whose expression differed significantly between patients and healthy individuals, and between before and after steroid treatment, were identified and validated using enzyme-linked immunosorbent assays. RESULTS: Pre-treatment sera from patients with IgG4-related disease was characterized by increased levels of immunoglobulins such as IgG1, IgG4; inflammatory factors such as α-1 antitrypsin (A1AT); and proteins associated with immune system regulation such as clusterin and leucine-rich α-2-glycoprotein (LRG-1). The serum levels of A1AT, LRG-1 and clusterin, during treatment with prednisolone for up to 12 months revealed that LRG-1 levels were halved after 1 month of treatment, comparable to those in healthy subjects; LRG-1 levels remained normal until the end of treatment. CONCLUSION: LRG-1 could serve as a novel biomarker of IgG4-related diseases.

Four-dimensional phase-contrast vastly undersampled isotropic projection reconstruction (4D PC-VIPR) MR evaluation of the renal arteries in transplant recipients: Preliminary results.

PURPOSE: To assess the performance of four-dimensional phase-contrast vastly undersampled isotropic projection reconstruction (4D PC-VIPR) at 3.0T in depicting intrarenal arteries compared with computed tomography angiography (CTA), and its correlation with arterial flowmetry in comparison with Doppler ultrasonography (DUS). MATERIALS AND METHODS: In our prospective single-arm study, subjects were 25 patients who underwent renal transplant-related surgery at our hospital between July 2011 and June 2015. In the morphological study, depictions of renal artery branches delineated by magnetic resonance angiography (MRA)/4D PC-VIPR without gadolinium contrast agent were compared in seven living transplant recipients with the same kidney delineated by CTA in seven living transplant donors. In the flowmetric study, flow velocities in the renal (main stem), segmental, and interlobar arteries during systole and diastole were measured in 12 recipients using noncontrast MRA/4D PC-VIPR, and were compared with those obtained from DUS. RESULTS: Concerning MRA, average confidence levels of delineation rated by six observers for secondary to third level renal artery branches were 82.9-100% and for the fourth to fifth branches were 60.8-89.7% (average kappa value of 0.588 [95% confidence interval: 0.522-0.653]). Total flow velocities measured using 4D PC-VIPR and DUS demonstrated significant correlations during both systole and diastole with acceptable bias (r = 0.902; P < 0.001 in systole and r = 0.734; P < 0.001 in diastole). CONCLUSION: 4D PC-VIPR was useful in generating both morphological and hemodynamic information for evaluation of transplant intrarenal arteries without the need for contrast media. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:595-603.

Intravenous administration of the selective toll-like receptor 7 agonist DSR-29133 leads to anti-tumor efficacy in murine solid tumor models which can be potentiated by combination with fractionated radiotherapy.

Strategies to augment anti-cancer immune responses have recently demonstrated therapeutic utility. To date clinical success has been achieved through targeting co-inhibitory checkpoints such as CTLA-4, PD-1, and PD-L1. However, approaches that target co-activatory pathways are also being actively being developed. Here we report that the novel TLR7-selective agonist DSR-29133 is well tolerated in mice and leads to acute immune activation. Administration of DSR-29133 leads to the induction of IFNα/γ, IP-10, TNFα, IL-1Ra and IL-12p70, and to a reduction in tumor burden in syngeneic models of renal cancer (Renca), metastatic osteosarcoma (LM8) and colorectal cancer (CT26). Moreover, we show that the efficacy of DSR-29133 was significantly improved when administered in combination with low-dose fractionated radiotherapy (RT). Effective combination therapy required weekly administration of DSR-29133 commencing on day 1 of a fractionated RT treatment cycle, whereas no enhancement of radiation response was observed when DSR-29133 was administered at the end of the fractionated RT cycle. Combined therapy resulted in curative responses in a high proportion of mice bearing established CT26 tumors which was dependent on the activity of CD8+ T-cells but independent of CD4+ T-cells and NK/NKT cells. Moreover, long-term surviving mice originally treated with DSR-29133 and RT were protected by a tumor-specific memory immune response which could prevent tumor growth upon rechallenge. These results demonstrate that DSR-29133 is a potent selective TLR7 agonist that when administered intravenously can induce anti-tumor immune responses that can be further enhanced through combination with low-dose fractionated RT.

Feasibility of magnetic resonance elastography for the pancreas at 3T.

PURPOSE: 1) To assess the usefulness of an elastic belt bracing the upper abdomen for reducing the miscalculated areas of the pancreas on 3.0T magnetic resonance elastography (MRE); 2) to test whether MRE can detect difference of stiffness between normal pancreas and the focal pancreatic diseases. MATERIALS AND METHODS: Using an initial eight normal volunteers, miscalculated areas were compared between MRE with the elastic belt and without the belt on 3.0T MRI. Then, using the belt, MRE of the normal pancreas was measured using 14 volunteers and 11 patients with focal pancreatic lesions. RESULTS: The median (95% confidence interval [CI]) percentages of correctly calculated areas were 57.4% (32.9-63.0) with the elastic belt and 35.3% (11.4-60.4) without the belt (P = 0.0078). The stiffness of each pancreatic segment of the normal volunteers (mean ± SE) was 2.37 ± 0.16 kPa for the head, 2.46 ± 0.17 kPa for the body, and 2.58 ± 0.26 kPa for the tail. The stiffness of seven pancreatic cancers was 6.06 ± 0.49 kPa, which was higher than the overall pancreatic stiffness of the normal volunteers (2.47 ± 0.11 kPa, P < 0.0001). Stiffness of the pancreatic lesions in the head of 6.03 ± 0.42 kPa, body of 5.57 ± 0.82 kPa, and tail of 5.9 ± 1.9 kPa were also higher than those of corresponding segments of the normal volunteers (P = 0.0011, 0.0029, and 0.029, respectively). CONCLUSION: With the elastic belt, miscalculation of the pancreatic stiffness was reduced. MRE showed differences of stiffness between normal pancreas and pancreatic lesions.

TLR7 tolerance is independent of the type I IFN pathway and leads to loss of anti-tumor efficacy in mice.

Systemic administration of small molecule toll-like receptor (TLR)-7 agonists leads to potent activation of innate immunity and to the generation of anti-tumor immune responses. However, activation of TLRs with small molecule agonists may lead to the induction of TLR tolerance, defined as a state of hyporesponsiveness to subsequent agonism, which may limit immune activation, the generation of anti-tumor responses and clinical response. Our data reveal that dose scheduling impacts on the efficacy of systemic therapy with the selective TLR7 agonist, 6-amino-2-(butylamino)-9-((6-(2-(dimethylamino)ethoxy)pyridin-3-yl)methyl)-7,9-dihydro-8H-purin-8-one (DSR-6434). In a preclinical model of renal cell cancer, systemic administration of DSR-6434 dosed once weekly resulted in a significant anti-tumor response. However, twice weekly dosing of DSR-6434 led to the induction of TLR tolerance, and no anti-tumor response was observed. We show that TLR7 tolerance was independent of type I interferon (IFN) negative feedback because induction of TLR7 tolerance was also observed in IFN-α/ß receptor knockout mice treated with DSR-6434. Moreover, our data demonstrate that treatment of bone marrow-derived plasmacytoid dendritic cells (BM-pDC) with DSR-6434 led to downregulation of TLR7 expression. From our data, dose scheduling of systemically administered TLR7 agonists can impact on anti-tumor activity through the induction of TLR tolerance. Furthermore, TLR7 expression on pDC may be a useful biomarker of TLR7 tolerance and aid in the optimization of dosing schedules involving systemically administered TLR7 agonists.

Discovery of 3H-imidazo[4,5-c]quinolin-4(5H)-ones as potent and selective dipeptidyl peptidase IV (DPP-4) inhibitors: use of a carboxylate prodrug to improve bioavailability.

We have previously reported a novel series of 3H-imidazo[4,5-c]quinolin-4(5H)-ones with potent dipeptidyl peptidase IV (DPP-4) inhibitory activity. However, these compounds showed poor oral absorption. We attempted in this study esterification of the carboxylic acid moiety to improve the compounds 1-4 plasma concentrations. Our efforts yielded 10h with a 5-methyl-2-oxo-1,3-dioxol-4-yl methyl ester as an S9/plasma-cleavable functionality. Compound 10h showed significantly high oral absorption and potent DPP-4 inhibition in vivo and decreased Zucker fatty rats glucose levels in the oral glucose tolerance test. Optimization of the ester moiety revealed that rapid conversion to the carboxyl form in both liver S9 fractions and serum was important for prodrugs not to be detected in the plasma after oral administration. In particular, lability in the serum was found to be an important characteristic. Through our investigation, we were able to develop a novel efficient synthetic method for construction of 3H-imidazo[4,5-c]quinolin-4(5H)-ones using intramolecular radical cyclization.

Reverse-genetic approach to verify physiological roles of rice phytoalexins: characterization of a knockdown mutant of OsCPS4 phytoalexin biosynthetic gene in rice.

A variety of labdane-related diterpenoids, including phytocassanes, oryzalexins and momilactones, were identified as phytoalexins in rice (Oryza sativa L.). Momilactone B was also isolated as an allelochemical exuded from rice roots. The biosynthetic genes of these phytoalexins have been identified, including six labdane-related diterpene cyclase genes such as OsCPS2, OsCPS4, OsKSL4, OsKSL7, OsKSL8 and OsKSL10. Here we identified an OsCPS4 knockdown mutant, cps4-tos, by screening Tos17 mutant lines using polymerase chain reaction. OsCPS4 encodes a syn-copalyl diphosphate synthase responsible for momilactones and oryzalexin S biosynthesis. Because Tos17 was inserted into the third intron of OsCPS4, the mature OsCPS4 mRNA was detected in the cps4-tos mutant as well as the wild type. Nevertheless, mature OsCPS4 transcript levels in the cps4-tos mutant were about one sixth those in the wild type. The cps4-tos mutant was more susceptible to rice blast fungus than the wild type, possibly due to lower levels of momilactones and oryzalexin S in the mutant. Moreover, co-cultivation experiments suggested that the allelopathic effect of cps4-tos against some kinds of lowland weeds was significantly lower than that of the wild type, probably because of lower momilactone content exuded from cps4-tos roots. A reverse-genetic strategy using the cps4-tos mutant showed the possible roles of momilactones not only as phytoalexins but also as allelopathic substances.

Laparoscopic Varicocelectomy Carried Out with the LigaSure Device in 52 Patients.

We describe the effective use of the bipolar vessel-sealing device: LigaSure for the division of the internal spermatic vessels in a laparoscopic varicocelectomy. A total of 52 males with varicocele (left-side n = 49, and bilateral n = 3) were included in this study. Blunt dissection was used to isolate the packet of spermatic vessels. The packet of spermatic vessels was divided using a bipolar diathermy system, the LigaSure Precise. It was clear that the operative time was significantly reduced compared to the method using clips, which was done before the development of this kind of device. In another experiment to examine the effect of vessel sealing, it was confirmed that the LigaSure has performance comparable to the clips. Despite the result that the Harmonic scalpel was less effective in vessel sealing, our study found it difficult to determine which is superior, LigaSure or clips, in terms of operative time, relapse rate and complication.

Skewed production of IL-6 and TGFß by cultured salivary gland epithelial cells from patients with Sjögren's syndrome.

OBJECTIVE: To determine the cytokine production profile of cultured salivary gland epithelial (SGE) cells obtained from patients with Sjögren's syndrome (SS). METHODS: SGE cells obtained from 9 SS patients and 6 normal controls were cultured in the presence of exogenous IFNγ. Cell proliferation and apoptosis in response to IFNγ were determined by WST1 assay and by FACS analysis. The concentrations of IL-6 and TGFß secreted into culture supernatants were analyzed by ELISA. RESULTS: IFNγ did not significantly affect the proliferation or apoptosis of SGE cells. However, IL-6 concentrations were higher, and TGFß concentrations were lower, in culture supernatants of SGE cells from SS patients than from normal controls. CONCLUSION: Cytokine production by SGE cells from SS patients showed a skewed balance compared with normal controls, with increased IL-6 and decreased TGFß secretion. This imbalance may be critical in the regulation of Treg/Th17 cells and may foster a pathogenic milieu that may be causative and predictive in SS.

Iron chelation therapy with deferasirox induced complete remission in a patient with chemotherapy-resistant acute monocytic leukemia.

BACKGROUND: A patient with chemotherapy-resistant acute monocytic leukemia who achieved complete remission (CR) after iron chelation therapy (ICT) with deferasirox is reported for the first time. A 73-year-old Japanese man with acute monocytic leukemia who was refractory to conventional remission induction chemotherapies achieved a partial response, with some improvement of his hemoglobin level and white blood cell count after gemtuzumab ozogamicin (GO) treatment. Seven months after GO treatment, the disease relapsed and the patient developed pancytopenia. He declined further chemotherapy, and started receiving 1,200-1,800 ml of packed red blood cell transfusion per month together with ICT with deferasirox (baseline serum ferritin level was 1,412 ng/ml). Twelve months after the initiation of deferasirox, the patient's serum ferritin level decreased to below 1,000 ng/ml and deferasirox was discontinued. Four months after discontinuation of deferasirox, the blood cell count normalized and the patient became transfusion-independent. Bone marrow aspiration and biopsy revealed hematological and cytogenetic CR. CONCLUSION: CR was achieved after ICT with deferasirox in a patient with acute myelogenous leukemia, suggesting that deferasirox may have an antileukemic effect in the clinical setting.

High-dose methotrexate with R-CHOP therapy for the treatment of patients with primary central nervous system lymphoma.

We describe MR-CHOP therapy, a novel treatment regimen consisting of high-dose methotrexate and R-CHOP that provides systemic anti-tumor activity with penetration of the blood-brain barrier in patients with newly diagnosed primary central nervous system lymphoma. The MR-CHOP regimen was administered with 2 g/m(2) of methotrexate and 375 mg/m(2) of rituximab on day 1, 750 mg/m(2) of cyclophosphamide on day 3, 50 mg/m(2) of doxorubicin on day 3, 1.4 mg/m(2) of vincristine on day 3 and 100 mg of prednisolone on days 1-5 in this pilot study of seven patients. Six cycles of MR-CHOP therapy were administered every 3 weeks, followed by high-dose chemotherapy with stem cell rescue in young patients, or an additional two cycles of 4 g/m(2) methotrexate and rituximab in older patients. The overall response rate was 100%, with 85.7% complete remission (CR). One patient showed partial response, relapsed and subsequently died. Another relapsed following CR, and was rescued by further salvage therapy. The others survive without relapse at a median observation period of 24 months. Hematological toxicity included grade 4 leukocytopenia in 4/7 and neutropenia in 5/7, which were transient and tolerated well. Non-hematological toxicities were tolerated well. The efficacy of this novel regimen as remission induction therapy was found to be promising in this pilot study, although the number of patients was small and follow-up short.

Complete response obtained by bortezomib plus dexamethasone in a patient with relapsed multiple myeloma with multiple plasmacytomas.

BACKGROUND: A case of relapsed multiple myeloma (MM) with multiple plasmacytomas of the parietal bone and the right orbit in which was achieved a complete response with bortezomib plus dexamethasone (BD) therapy is reported. A Japanese woman with Bench-Jones lambda-type MM who achieved a plateau phase with nine courses of melphalan plus prednisolone therapy complained of right exophthalmos and numbness around her mouth. Computed tomographic (CT) scan and T2-weighted magnetic resonance imaging showed tumours at the parietal bone and the right orbit. A tumour biopsy from the parietal bone revealed the histological morphology of a plasmacytoma. She was therefore diagnosed with relapsed MM with multiple plasmacytomas, and received BD therapy. A CT scan after the end of the second course of treatment revealed the disappearance of the plasmacytomas. At the end of the fifth course, no lambda light chain was detected by immunofixation of serum and urine, and the pathological plasma cells in bone marrow were fewer than 5%; therefore, she had achieved a complete response. The time to disease progression from the first course of BD therapy and the treatment-free interval were 400 days and 134 days, respectively. CONCLUSION: This case report indicates that bortezomib may be a promising agent for MM with multiple plasmacytomas.

[Primary neurolymphomatosis of the cervical nerve root].

A 74-year-old woman was admitted with muscle weakness and sharp pain in her upper limbs. On (18)FDG-PET, abnormal accumulation was noted on both sides of the brachial plexus at the cervical spinal cord. A diagnosis of primary peripheral nerve neurolymphomatosis was made based on biopsy of the third cervical nerve. Following R-CHOP therapy, the abnormal accumulation of (18)FDG-PET scan disappeared. However, disturbance of consciousness occurred 6 months later and recurrence as multiple brain tumors was detected. Although salvage chemotherapy was performed, the patient died of overwhelming sepsis. Primary peripheral nerve neurolymphomatosis is extremely rare. Early distinct diagnosis using (18)FDG-PET and combination chemotherapy of rituximab and high dose methotrexate may improve the outcome for such patients.

[Very good partial response and long time to progression by short-term bortezomib plus dexamethasone therapy for a patient with relapsed and refractory multiple myeloma-a case report].

A 63-year-old female with relapsed and refractory multiple myeloma, in whom the duration of disease and history of chemotherapy were 15 years and 9 years, respectively, was treated with bortezomib and dexamethasone. A very good partial response and about 500 days to progression were obtained at a total dose of 10.2 mg bortezomib, until the day 4 injection of the second course. Bone pain has completely disappeared. These findings suggested that the therapeutic efficacy of bortezomib may persist over a long period regardless of the duration of chemotherapy. When a favorable response is obtained, but continuous therapy with bortezomib is difficult for reasons such as adverse events (other than refractory to bortezomib), careful observation may be one of the important options.

MRSA-pyomyositis in a patient with acute myelogenous leukemia after intensive chemotherapy.

BACKGROUND: A case of methicillin-resistant Staphylococcus aureus (MRSA)-pyomyositis in association with acute myelogenous leukemia (AML) is reported. MRSA-sepsis developed in a 51-year-old Japanese man with AML, during the neutropenic period after high-dose 1-beta-d-arabinofuranosylcytosine (Ara-C). Although the MRSA-sepsis initially improved with arbekacin sulfate (ABK) administration, a high fever recurred with left thigh pain despite recovery of the neutrophil count after ABK was stopped. A computed tomographic (CT) scan showed a low-density area in the left quadriceps femoris muscle, which led to a diagnosis of pyomyositis. MRSA was cultured from the abscess aspirates. The fever and thigh pain disappeared after administration of ABK and minocycline hydrochloride (MINO), and the abscess completely disappeared with the oral administration of levofloxacin (LVFX) for about 3 months. CONCLUSION: If an immunocompromised patient complains of fever and muscle pain after intensive chemotherapy, MRSA-pyomyositis should be considered.

Intravascular large B cell lymphoma: proposed of the strategy for early diagnosis and treatment of patients with rapid deteriorating condition.

We summarize our experience and propose methods for early diagnosis and treatment of intravascular large B cell lymphoma (IVL). A total of 16 patients with IVL between 1994 and 2007 were included and analyzed in this study. Predicted survival durations were short until September 2003. However, there have been marked improvement since the introduction of rituximab, and all patients responded to treatment and survived for more than 1 year following diagnosis of IVL. We propose an early clinical diagnostic strategy for starting treatment for IVL patients with quite poor performance status (PS) and in whom time is a limiting factor: (1) age >40 years, (2) fever above 38 degrees C with poor PS (ECOG 2-4), (3) lactate dehydrogenase (LDH) more than twice the upper limit of the normal level and/or sIL2R >5,000 IU/ml in serum, (4) worsening PS and/or elevation of serum LDH on a daily basis, and (5) confirmation of pathological lymphoid cells in peripheral blood or bone marrow smear and/or flow cytometry. Although accurate pathological diagnosis is quite important, time is a limiting factor for most of IVL patients. In such cases, we can start chemotherapy based on early clinical diagnostic strategy with high sensitivity and obtain good clinical outcome.

Cloning and characterization of cDNAs encoding ent-copalyl diphosphate synthases in wheat: insight into the evolution of rice phytoalexin biosynthetic genes.

In vitro assays using recombinant enzymes enabled three cDNAs encoding ent-copalyl diphosphate synthases to be identified in wheat (Triticum aestivum): TaCPS1, TaCPS2, and TaCPS3. The phylogenetic tree and expression analyses suggest that TaCPS3 is responsible for gibberellin biosynthesis, while TaCPS1 and TaCPS2 are possible functional homologs of diterpene cyclase genes OsCPS2 and OsCPS4 involved in phytoalexin biosynthesis in rice.

Comparison of the enzymatic properties of ent-copalyl diphosphate synthases in the biosynthesis of phytoalexins and gibberellins in rice.

The rice genome contains two ent-copalyl diphosphate synthase genes: OsCPS1 acts in gibberellin (phytohormone) biosynthesis, and OsCPS2/OsCyc2 acts in the synthesis of oryzalexins A-F and phytocassanes A-E (phytoalexins). We characterized the enzymatic properties of recombinant OsCPS2/OsCyc2 fused with a tag-protein at the N-terminus, and compared them to those of OsCPS1. Several enzymatic properties of OsCPS2/OsCyc2, including the optimal pH, optimal temperature, divalent cation requirement, and kinetic values for the geranylgeranyl diphosphate (GGDP) substrate, were almost the same as those of OsCPS1. However, OsCPS2/OsCyc2 activity was not inhibited by 50-60 muM GGDP substrate, by which the OsCPS1 activity was inhibited. Furthermore, the OsCPS1 activity exhibited approximately 70% inhibition by 100 muM Amo-1618 (a gibberellin biosynthetic inhibitor), whereas the OsCPS2/OsCyc2 activity exhibited approximately 10% inhibition. These results indicate that the properties of OsCPS2/OsCyc2 were partially different from those of OsCPS1, although OsCPS2/OsCyc2 catalyzes the same reaction step as OsCPS1.

Chelation-assisted electrocyclic reactions of 3-alkenyl-2,2'-bipyridines: an efficient method for the synthesis of 5,6-dihydro-1,10-phenanthroline and 1,10-phenanthroline derivatives.

An efficient method for the synthesis of substituted 5,6-dihydro-1,10-phenanthrolines and 1,10-phenanthrolines has been developed by means of the chelation-assisted photochemical electrocyclic reactions of 3-alkenyl-2,2'-bipyridines.