Israel Institute for Biological Research

Other

The Purdue Frederick Company

Nsc Therapeutics Gmbh

State of Israel, Represented by the Prime Minister's Office, Israel

University of Pittsburgh

State of Israel, Represented by Prime Minister's Office Israel Institute

State of Israel, Israel Institute of Biological Research

State of Israel, Represented by Prime Minister's Office, Israel

Abraham Fisher

Nira Bar-Ner

Sasson Cohen

Ishai Karton

Yishai Karton

Aharon Levy

Yona Grunfeld

Haim Meshulam

Oren Shlomo Somekh

Eliahu Heldman

Manfred Windisch

Victoria Nachum

Dov Barak

Daniele Marciano

Roger Nitsch

Donald J Abraham

Yoffi Segall

Dror Meiri

Ezra Shirin

Eliahu Heidman

Isaac Nativ

Yona Sivan

Yishal Karton

Drora Levy

Michael Y Spiegelstein

Jacob Grunwald

Moshe Kushnir

Israel Hanin

Stefan Grathwohl

Ishal Karton

Nira Bar-ner

Provided are M1 muscarinic acetylcholine receptor (mAChR) agonists, for use in the treatment of a neurological or neurodegenerative disease by promoting microglia and/or macrophage viability and/or activation. Microglia and macrophage survival and activation are thereby achieved by increasing levels of sTREM2 released by microglia cells. In addition, pharmaceutical compositions and methods of preparing the same are described, which are suitable for the treatment or prevention of conditions or diseases that require microglia and/or macrophage modulation, as well as methods for monitoring treatments and enhancing microglia and/or macrophage survival and/or activation.

Compounds and methods for use in the treatment of microglia-mediated disorders

Provided are novel crystalline forms of a spiro-compound which acts as a muscarinic acetylcholine receptor agonist. In particular, isolated crystalline polymorphs of (S)-2-ethyl-8-methyl-1-thia-4,8-diazaspiro[4.5]decane-3-one are described which have favorable properties in pharmaceutical manufacture. Also provided are methods to prepare said crystalline polymorphs, and to convert them into each other as well as methods for preparing medicaments containing the same which are suitable for use in the treatment of diseases and disorders that respond to modulation of the muscarinic acetylcholine receptor.

Crystalline polymorphs of a muscarinic acetylcholine receptor agonist

There are provided certain bicyclic heterocyclic compounds that act as M1 muscarinic receptor modulators. Compositions containing these compounds and their use are also disclosed.

Bicyclic heterocyclic spiro compounds

There are disclosed bicyclic heterocyclic spiro compounds; pharmaceutical compositions comprising these compounds; and methods for the treatment in a mammal of diseases and conditions which are susceptible to modulation of the M1 muscarinic receptor, including Alzheimer's disease, insulin resistance syndrome and type 2 diabetes. Other embodiments are also disclosed.

There are provided methods for the treatment of diseases involving dysfunction of the peripheral and central nervous system comprising administering one or more spiro compounds. Also provided are pharmaceutical compositions useful in such methods, compounds for use in the preparation of such pharmaceutical compositions, processes for preparing compounds useful in the practice of such methods, and some novel such compounds per se.

Methods and compositions for treatment of central and peripheral nervous system disorders and novel compounds useful therefor

A method of transmitting data bits over a modem connection. The method includes receiving a first stream of data bits, by a first modem, performing a first set of one or more communication tasks on the first stream of bits, by the first modem, so as to generate a second stream of bits, modulating the second stream of bits, by the first modem, so as to form a modulated signal, transmitting the modulated signal from the first modem to a second modem, demodulating the modulated signal by the second modem, so as to form a third stream of bits, performing on the third stream of bits, a second set of zero or more communication tasks, including a different number of tasks than the first set of tasks, so as to form a fourth stream of bits, and transmitting the fourth stream of bits to a communication unit over a packet based network.

Distributed modem

A method for transmitting data signals in full duplex with echo cancellation between a first and a second modem connected by a two-wire channel, wherein a data signal is a function of at least one data symbol in a stream of data symbols generated by a modem comprising: determining echo cancellation coefficients for the first modem; transmitting data signals in full duplex between the two modems using the echo cancellation coefficients to cancel echoes in data signals received by the first modem; providing at least one hiatus in data symbol generation by the second modem while continuing data symbol generation by the first modem at a time at which echo cancellation using the echo cancellation coefficients is effective in canceling echoes in data signals received by the first modem; and updating the first modem echo cancellation coefficients during the at least one second modem hiatus.

Adaptive echo canceling

A method of establishing a fax connection on a link which is a portion of a composite connection. The method includes transmitting at least some signals of a negotiation procedure on the link and initiating a retrain on the connection, without identifying a problem on the connection of the link, the retrain being initiated after transmitting the at least some signals of the negotiation procedure but before transmitting data on the data channel of the link due to the negotiation procedure.

Real time fax over packet based network

There are provided methods for the treatment of diseases involving dysfunction of the peripheral and central nervous system comprising administering one or more Spiro compounds. Also provided and pharmaceutical compositions useful in such methods, compounds for use in the preparation of such pharmaceutical compositions, processes for preparing compounds useful in the practice of such methods, and some novel such compounds per se.

Methods and pharmaceutical compositions for treatment of central and peripheral nervous system disorders and compounds useful therefor

Compounds useful for treating diseases of the central or peripheral nervous system in mammals have formulae I-XII ##STR1## wherein ring A or A' together with the spiro-carbon atom constitutes a bridged or unbridged ring containing one or two ring nitrogen atoms; and the other symbols have specified values, subject to certain conditions.

Aza spiro compounds acting on the cholinergic system with muscarinic

Compounds useful for treating diseases of the central or peripheral nervous system in mammals have formulae I-XIII: ##STR1## wherein ring A or A' together with the spiro-carbon atom constitutes a bridged or unbridged ring containing one or two ring nitrogen atoms; and the other symbols have specified values, subject to certain conditions.

Spiro compounds containing five-membered rings

The invention relates to compounds (I) for treating diseases of the central and peripheral nervous system, including enantiomers, racemates and acid addition and quaternary salts, ##STR1## wherein Q is selected from two H atoms, (CH.sub.2).sub.m and C(CH.sub.3).sub.2 where m is 1, 2 or 3 and n and p are; each independently 0, 1, 2 or 3, provided that n+p=1-3, and R.sup.0 is H, methyl or OH; the moiety ##STR2## R is selected from H, NH.sub.2, NH-C.sub.1-6 -alkyl, N(C.sub.1-6 -alkyl).sub.2, C.sub.1-6 -alkyl, C.sub.2-6 -alkenyl, C.sub.2-6 -alkynyl, C.sub.3-7 - cycloalkyl, C.sub.1-6 -alkyl substituted by 1-6 halogen atoms, hydroxy- C.sub.1-6 -alkyl, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, C.sub.1-6 -alkoxy-C.sub.1-6 -alkyl, carboxy-C.sub.1-6 -alkyl, (C.sub.1-6 -alkoxy)carbonyl-C.sub.1-6 -alkyl, amino-C.sub.1-6 -alkyl, mono-(C.sub.1-6 -alkyl)amino-C.sub.1-6 -alkyl, di-(C.sub.1-6 -alkyl)amino-C.sub.1-6 -alkyl, 2-oxo-pyrrolidin-1-yl-methyl, aryl, diarylmethylol, and C.sub.1-6 -alkyl substituted by one or two aryl groups; R' is independently selected from the group from which R is selected and C.sub.1-6 -alkanoyl and arylcarbonyl; and aryl denotes unsubstituted phenyl or phenyl substituted by 1-3 substituents selected from halogen, C.sub.1-6 -alkyl, C.sub.1-6 -alkoxy and CF.sub.3, subject to certain provisos.

Certain 1-methyl-piperidine-4-spiro-4'-(1'-3'-oxazolines) and

A pharmaceutical composition is disclosed comprising (-)-cis-2-methylspiro(1,3-oxathiolan-5,3')quinuclidine, and/or the pharmaceutically compatible acid addition salts thereof, together with at least one of physostigmine, tetrahydroaminoacridine, choline, lecithin, piracetam, aniracetam, pramiracetam, oxiracetam, 4-aminopyridine, 3,4-diaminopyridine, somatostatin, pirenzepine, N-methylatropine, N-butylscopolamine, scopolamine, clonidine, quanfamicine and Nerve Growth Factor. Also disclosed is a method for treating senile dementia of Alzheimer's type, which comprises coadministering to a patient in need thereof an effective dose of the spiro compound together with at least one other compound selected from those listed above.

Pharmaceutical composition comprising a spiro oxathiolon/quinuclidine

The invention relates to novel compounds (I) for treating diseases of the central and peripheral nervous system: ##STR1## including enantiomers, racemates and acid addition and quaternary salts thereof, wherein one of X and Y is O and the other of X and Y is N; Q is (CH.sub.2).sub.n or C(CH.sub.3).sub.2 where n is 1, 2 or 3 and the bridge --Q-- is attached at one end to position 1 and at the other end to position 4 or 5, and R.degree. is hydrogen, methyl or hydroxyl; in the moiety ##STR2## the line connecting Z and Y signifies a double bond when X--Z is O--C--R and Y is N, and a single bond when X--Z is N.dbd.C--R and Y is O; Z is C--R wherein R is selected from hydrogen, NH.sub.2, NH-R' (R'=C.sub.1-6 -alkyl), N(R').sub.2, R', C.sub.2-6 -alkenyl, C.sub.2-6 -alkynyl, C.sub.3-7 -cycloalkyl, R' substituted by hydroxy or by 1-6 halogen atoms, R'O-C.sub.1-6 -alkyl, carboxy-C.sub.1-6 -alkyl, R'OCO-C.sub.1-6 -alkyl, amino-C.sub.1-6 -alkyl, R''NH-C.sub.1-6 -alkyl, (R').sub.2 N-C.sub.1-6 -alkyl, 2-oxo-pyrrolidin-1-ylmethyl, aryl, diarylmethylol, and R' substituted by one or two aryl groups, wherein aryl denotes phenyl optionally substituted by 1-3 halogens, R', R'O and(or) CF.sub.3. Also claimed are compounds wherein the line connecting Z and Y signifies the absence of a bond, X is O, Z is H and Y is NH.sub.2, NO.sub.2 or N.sub.3.

Growing community of inventors

Holon, Israel

Abraham Fisher