Nasser Yehia - Academia.edu (original) (raw)

Papers by Nasser Yehia

Cerebral edema is a life-threatening condition that can cause permanent brain damage or death if ... more Cerebral edema is a life-threatening condition that can cause permanent brain damage or death if left untreated. Existing therapies aim at mitigating the associated elevated intracranial pressure, yet they primarily alleviate pressure rather than preventing edema formation. Prophylactic anti-edema therapy necessitates novel drugs targeting edema formation. Aquaporin 4 (AQP4), an abundantly expressed water pore in mammalian glia and ependymal cells, has been proposed to be involved in cerebral edema formation. A series of novel compounds have been tested for their potential inhibitory effects on AQP4. However, selectivity, toxicity, functional inhibition, sustained therapeutic concentration, and delivery into the central nervous system are major challenges. Employing extensive DFT calculations, we identified a previously unreported thermodynamically stable tautomer of the recently identified AQP4-specific inhibitor TGN-020. This novel form, featuring a distinct hydrogen bonding patte...

European Journal of Organic Chemistry, Apr 25, 2005

European Journal of Organic Chemistry, 2003

... Appel, T., Yehia, N., Baumeister, U., Hartung, H., Kluge, R., Ströhl, D. and Fanghänel, E. (2... more ... Appel, T., Yehia, N., Baumeister, U., Hartung, H., Kluge, R., Ströhl, D. and Fanghänel, E. (2003), Electrophilic Cyclisation of Bis(4-methoxybenzylthio)acetylene − Competition Between Ar 2 -6 and ... An NOE was found between 5-H and the methylene protons of the 6-ethoxy group. ...

Arkivoc, Apr 29, 2007

The synthesis of a novel class of potential aspartyl-protease inhibitors is described. Arrays of ... more The synthesis of a novel class of potential aspartyl-protease inhibitors is described. Arrays of 1,4,5-trisubstituted 1-(4-piperidyl)-imidazoles have been assembled by parallel synthesis using an isocyanide-based multi component reaction (vL-3CR).

Journal of Organic Chemistry, Jun 20, 1998

Substituted 1H-2-benzothiopyrans find applications as pharmaceutically active compounds or syntho... more Substituted 1H-2-benzothiopyrans find applications as pharmaceutically active compounds or synthons for more complex sulfur heterocycles. However, restricted variability in their synthesis limits the application for research or industrial purposes. To develop a direct and fast route to substituted and functionalized 1H-2-benzothiopyrans, we investigated the ring closure of symmetrical bis(arylmethylthio)acetylenes with iodine monochloride or bromine. This facile reaction yielded 1H-3-halo-4-arylmethylthio-2-benzo- and 2-naphthothiopyrans via postulated vinyl cations in yields of 47−86%. Substituted 2-benzo- and 2-naphthothiopyrylium salts were prepared by hydride abstraction with triphenylcarbenium tetrafluoroborate from the products, further enhancing the synthetic potential of the found cyclization reaction.

Phosphorus Sulfur and Silicon and The Related Elements, 1999

The intramolecular cyclization of bis(arylmethylthio)acetylenes by electrophiles like ICl, Br2, P... more The intramolecular cyclization of bis(arylmethylthio)acetylenes by electrophiles like ICl, Br2, POCl3, and Ph3CBF4 to substituted 1H-2-benzothiopyrans, -thiopyrylium salts and in a specific case to a 2-thiaspiro[5,4]-deca-3,6,9-trien-8-one is described.

ChemInform, Jun 18, 2010

Versatile Route to Functionalized 1H-2-Benzothiopyrans and 1H-2-Naphthothiopyrans by Electrophili... more Versatile Route to Functionalized 1H-2-Benzothiopyrans and 1H-2-Naphthothiopyrans by Electrophilic Cyclization of Bis(arylmethylthio)acetylenes: 2-Benzo-and 2-Naphthothiopyrylium Salts.-Treatment of bis(arylmethylthio)acetylenes with ICl and sometimes with Br 2 results in efficient formation of thiopyrans. The ring closure of the derivative (IIIf) proceeds with high regioselectivity. The thiopyrans and their salts are pharmacologically and synthetically important compounds.

Clinical Cancer Research, 2003

ChemInform, 2004

Dedicated to Dr. Hans-Ulrich Wagner on the occasion of his 65 th birthday The coupling-isomerizat... more Dedicated to Dr. Hans-Ulrich Wagner on the occasion of his 65 th birthday The coupling-isomerization reaction (CIR) of electron-deficient halides 1 with N-[1-(hetero)arylprop-2-ynyl] tosyl amides 2 leads to the formation of N-tosyl enimines 3, in good to excellent yields. These electron deficient heterodienes are perfectly suited for Diels-Alder reactions with inverse electron demand. In the sense of a one-pot reaction a three-component CIR-cyclocondensation sequence of 1, 2a, and diethyl ketene acetal gives rise to the formation of 2-ethoxy 6-(p-anisyl)pyridines 4 in moderate to good yields.

Tetrahedron Letters, 2002

A Novel Four Component One-Pot Access to Pyrindines and Tetrahydroquinolines.-Pd-catalyzed coupli... more A Novel Four Component One-Pot Access to Pyrindines and Tetrahydroquinolines.-Pd-catalyzed coupling of aryl bromides (I) and terminal alkynes (II) generates chalcones in situ. Subsequent Stark enamine alkylation with morpholine cycloalkanones (III) yields 1,5-diketones (IV). Additionally, one-pot conversion of the 1,5-diketones obtained to cycloalkyl annealed pyridines (V) is also described.-(YEHIA, N.

The Journal of Organic Chemistry, 1998

Substituted 1H-2-benzothiopyrans find applications as pharmaceutically active compounds or syntho... more Substituted 1H-2-benzothiopyrans find applications as pharmaceutically active compounds or synthons for more complex sulfur heterocycles. However, restricted variability in their synthesis limits the application for research or industrial purposes. To develop a direct and fast route to substituted and functionalized 1H-2-benzothiopyrans, we investigated the ring closure of symmetrical bis(arylmethylthio)acetylenes with iodine monochloride or bromine. This facile reaction yielded 1H-3-halo-4-arylmethylthio-2-benzo- and 2-naphthothiopyrans via postulated vinyl cations in yields of 47−86%. Substituted 2-benzo- and 2-naphthothiopyrylium salts were prepared by hydride abstraction with triphenylcarbenium tetrafluoroborate from the products, further enhancing the synthetic potential of the found cyclization reaction.

European Journal of Organic Chemistry, 2005

Annelated (dihydropyridines, tetrahydroquinolines, naphthyridines) and substituted pyridines can ... more Annelated (dihydropyridines, tetrahydroquinolines, naphthyridines) and substituted pyridines can be synthesized in moderate to good yields in a consecutive one‐pot, four‐component process by a coupling–isomerization–enamine addition–cyclocondensation sequence of an electron poor (hetero)aryl halide, a terminal propargyl alcohol, an enamine, and ammonium chloride. After the coupling–isomerization sequence a Diels–Alder reaction with inverse electron demand of the intermediate chalcone and the enamine furnishes a cycloadduct 6 that was unambiguously characterized by X‐ray structure analysis as well as the 1,5‐diketones 4b and 4g — the corresponding hydrolysis products — and the pyridine derivatives 11e (dihydropyridine), 11i (tetrahydroquinoline), 11o (naphthyridine), and 14b and 14c (ethyl nicotinoates). Additionally, quantum chemical calculations support the stepwise nature of the enamine cycloaddition. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Bioorganic & Medicinal Chemistry Letters, 2004

Arkivoc, 2007

The synthesis of a novel class of potential aspartyl-protease inhibitors is described. Arrays of ... more The synthesis of a novel class of potential aspartyl-protease inhibitors is described. Arrays of 1,4,5-trisubstituted 1-(4-piperidyl)-imidazoles have been assembled by parallel synthesis using an isocyanide-based multi component reaction (vL-3CR).

Phosphorus, Sulfur, and Silicon and the Related Elements, 1999

The intramolecular cyclization of bis(arylmethylthio)acetylenes by electrophiles like ICl, Br2, P... more The intramolecular cyclization of bis(arylmethylthio)acetylenes by electrophiles like ICl, Br2, POCl3, and Ph3CBF4 to substituted 1H-2-benzothiopyrans, -thiopyrylium salts and in a specific case to a 2-thiaspiro[5,4]-deca-3,6,9-trien-8-one is described.

Cerebral edema is a life-threatening condition that can cause permanent brain damage or death if ... more Cerebral edema is a life-threatening condition that can cause permanent brain damage or death if left untreated. Existing therapies aim at mitigating the associated elevated intracranial pressure, yet they primarily alleviate pressure rather than preventing edema formation. Prophylactic anti-edema therapy necessitates novel drugs targeting edema formation. Aquaporin 4 (AQP4), an abundantly expressed water pore in mammalian glia and ependymal cells, has been proposed to be involved in cerebral edema formation. A series of novel compounds have been tested for their potential inhibitory effects on AQP4. However, selectivity, toxicity, functional inhibition, sustained therapeutic concentration, and delivery into the central nervous system are major challenges. Employing extensive DFT calculations, we identified a previously unreported thermodynamically stable tautomer of the recently identified AQP4-specific inhibitor TGN-020. This novel form, featuring a distinct hydrogen bonding patte...

European Journal of Organic Chemistry, Apr 25, 2005

European Journal of Organic Chemistry, 2003

... Appel, T., Yehia, N., Baumeister, U., Hartung, H., Kluge, R., Ströhl, D. and Fanghänel, E. (2... more ... Appel, T., Yehia, N., Baumeister, U., Hartung, H., Kluge, R., Ströhl, D. and Fanghänel, E. (2003), Electrophilic Cyclisation of Bis(4-methoxybenzylthio)acetylene − Competition Between Ar 2 -6 and ... An NOE was found between 5-H and the methylene protons of the 6-ethoxy group. ...

Arkivoc, Apr 29, 2007

The synthesis of a novel class of potential aspartyl-protease inhibitors is described. Arrays of ... more The synthesis of a novel class of potential aspartyl-protease inhibitors is described. Arrays of 1,4,5-trisubstituted 1-(4-piperidyl)-imidazoles have been assembled by parallel synthesis using an isocyanide-based multi component reaction (vL-3CR).

Journal of Organic Chemistry, Jun 20, 1998

Substituted 1H-2-benzothiopyrans find applications as pharmaceutically active compounds or syntho... more Substituted 1H-2-benzothiopyrans find applications as pharmaceutically active compounds or synthons for more complex sulfur heterocycles. However, restricted variability in their synthesis limits the application for research or industrial purposes. To develop a direct and fast route to substituted and functionalized 1H-2-benzothiopyrans, we investigated the ring closure of symmetrical bis(arylmethylthio)acetylenes with iodine monochloride or bromine. This facile reaction yielded 1H-3-halo-4-arylmethylthio-2-benzo- and 2-naphthothiopyrans via postulated vinyl cations in yields of 47−86%. Substituted 2-benzo- and 2-naphthothiopyrylium salts were prepared by hydride abstraction with triphenylcarbenium tetrafluoroborate from the products, further enhancing the synthetic potential of the found cyclization reaction.

Phosphorus Sulfur and Silicon and The Related Elements, 1999

The intramolecular cyclization of bis(arylmethylthio)acetylenes by electrophiles like ICl, Br2, P... more The intramolecular cyclization of bis(arylmethylthio)acetylenes by electrophiles like ICl, Br2, POCl3, and Ph3CBF4 to substituted 1H-2-benzothiopyrans, -thiopyrylium salts and in a specific case to a 2-thiaspiro[5,4]-deca-3,6,9-trien-8-one is described.

ChemInform, Jun 18, 2010

Versatile Route to Functionalized 1H-2-Benzothiopyrans and 1H-2-Naphthothiopyrans by Electrophili... more Versatile Route to Functionalized 1H-2-Benzothiopyrans and 1H-2-Naphthothiopyrans by Electrophilic Cyclization of Bis(arylmethylthio)acetylenes: 2-Benzo-and 2-Naphthothiopyrylium Salts.-Treatment of bis(arylmethylthio)acetylenes with ICl and sometimes with Br 2 results in efficient formation of thiopyrans. The ring closure of the derivative (IIIf) proceeds with high regioselectivity. The thiopyrans and their salts are pharmacologically and synthetically important compounds.

Clinical Cancer Research, 2003

ChemInform, 2004

Dedicated to Dr. Hans-Ulrich Wagner on the occasion of his 65 th birthday The coupling-isomerizat... more Dedicated to Dr. Hans-Ulrich Wagner on the occasion of his 65 th birthday The coupling-isomerization reaction (CIR) of electron-deficient halides 1 with N-[1-(hetero)arylprop-2-ynyl] tosyl amides 2 leads to the formation of N-tosyl enimines 3, in good to excellent yields. These electron deficient heterodienes are perfectly suited for Diels-Alder reactions with inverse electron demand. In the sense of a one-pot reaction a three-component CIR-cyclocondensation sequence of 1, 2a, and diethyl ketene acetal gives rise to the formation of 2-ethoxy 6-(p-anisyl)pyridines 4 in moderate to good yields.

Tetrahedron Letters, 2002

A Novel Four Component One-Pot Access to Pyrindines and Tetrahydroquinolines.-Pd-catalyzed coupli... more A Novel Four Component One-Pot Access to Pyrindines and Tetrahydroquinolines.-Pd-catalyzed coupling of aryl bromides (I) and terminal alkynes (II) generates chalcones in situ. Subsequent Stark enamine alkylation with morpholine cycloalkanones (III) yields 1,5-diketones (IV). Additionally, one-pot conversion of the 1,5-diketones obtained to cycloalkyl annealed pyridines (V) is also described.-(YEHIA, N.

The Journal of Organic Chemistry, 1998

Substituted 1H-2-benzothiopyrans find applications as pharmaceutically active compounds or syntho... more Substituted 1H-2-benzothiopyrans find applications as pharmaceutically active compounds or synthons for more complex sulfur heterocycles. However, restricted variability in their synthesis limits the application for research or industrial purposes. To develop a direct and fast route to substituted and functionalized 1H-2-benzothiopyrans, we investigated the ring closure of symmetrical bis(arylmethylthio)acetylenes with iodine monochloride or bromine. This facile reaction yielded 1H-3-halo-4-arylmethylthio-2-benzo- and 2-naphthothiopyrans via postulated vinyl cations in yields of 47−86%. Substituted 2-benzo- and 2-naphthothiopyrylium salts were prepared by hydride abstraction with triphenylcarbenium tetrafluoroborate from the products, further enhancing the synthetic potential of the found cyclization reaction.

European Journal of Organic Chemistry, 2005

Annelated (dihydropyridines, tetrahydroquinolines, naphthyridines) and substituted pyridines can ... more Annelated (dihydropyridines, tetrahydroquinolines, naphthyridines) and substituted pyridines can be synthesized in moderate to good yields in a consecutive one‐pot, four‐component process by a coupling–isomerization–enamine addition–cyclocondensation sequence of an electron poor (hetero)aryl halide, a terminal propargyl alcohol, an enamine, and ammonium chloride. After the coupling–isomerization sequence a Diels–Alder reaction with inverse electron demand of the intermediate chalcone and the enamine furnishes a cycloadduct 6 that was unambiguously characterized by X‐ray structure analysis as well as the 1,5‐diketones 4b and 4g — the corresponding hydrolysis products — and the pyridine derivatives 11e (dihydropyridine), 11i (tetrahydroquinoline), 11o (naphthyridine), and 14b and 14c (ethyl nicotinoates). Additionally, quantum chemical calculations support the stepwise nature of the enamine cycloaddition. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Bioorganic & Medicinal Chemistry Letters, 2004

Arkivoc, 2007

The synthesis of a novel class of potential aspartyl-protease inhibitors is described. Arrays of ... more The synthesis of a novel class of potential aspartyl-protease inhibitors is described. Arrays of 1,4,5-trisubstituted 1-(4-piperidyl)-imidazoles have been assembled by parallel synthesis using an isocyanide-based multi component reaction (vL-3CR).

Phosphorus, Sulfur, and Silicon and the Related Elements, 1999

The intramolecular cyclization of bis(arylmethylthio)acetylenes by electrophiles like ICl, Br2, P... more The intramolecular cyclization of bis(arylmethylthio)acetylenes by electrophiles like ICl, Br2, POCl3, and Ph3CBF4 to substituted 1H-2-benzothiopyrans, -thiopyrylium salts and in a specific case to a 2-thiaspiro[5,4]-deca-3,6,9-trien-8-one is described.